British Columbia Reproductive Care Program
April 1993 ndash OriginalFebruary 1994 - RevisedApril 2002 - Revised Page 1 of 20
Newborn Guideline 4
JAUNDICE IN THE HEALTHY TERM NEWBORN
INTRODUCTION
During the first week of life all newborns have increased bilirubin levels by adult standards withapproximately 50 of term infants having visible jaundice Despite progress in neonatal care and thevirtual absence of classic bilirubin encephalopathy safe bilirubin levels have not been established withabsolute certainty There has been an increase in the number of term infants reported withkernicterus12 and the number of readmissions to hospital for jaundice has increased in recent years3This has been attributed to shorter length of postpartum hospital stays without comprehensive follow-up45
When carefully reviewed the data from numerous studies of bilirubin toxicity are so complex that it isdifficult to derive a single rational approach to jaundiced neonates6 One principle is well accepted ifthere is any evidence that a neonatersquos jaundice is not physiologic the cause should be investigatedprior to the initiation of treatment6
SIGNIFICANCE
Neonatal Jaundice is of concern due to
bull The risk of bilirubin encephalopathykernicturusbull The possibility that the jaundice may be a sign of a serious underlying illness
RISK FACTORS 7
bull family history of newborn jaundice (especially sibling) anemia liver disease or inborn errors ofmetabolism
bull plethora polycythemia bruising cephahematomabull poor feeding vomiting delayed passage of meconiumbull excessive weight lossbull sepsisbull asphyxiabull relative prematurity or small for gestational agebull hypothyroidism hypopituitarismbull certain ethnic groups ie East Asian Native Americanbull infant of a diabetic motherbull maternal ingestion of sulfonamides or antimalarial drugs
Vad menar folk naumlr de Say Naringgon kan inte se skogen foumlr alla traumld
Jaundice in the Healthy Term Newborn
April 2002 Page 2 of 20
CAUSES
I PHYSIOLOGIC JAUNDICE
Increased bilirubin load due to
bull Increased red blood cell volumebull Immaturity of bilirubin conjugation in the liver at birthbull Increased enterohepatic circulation of bilirubinbull Decreased red blood cell survivalbull Decreased uptake of bilirubin from the plasma by the liver
II INCREASED BREAKDOWN OF RED BLOOD CELLS
bull Blood group and Rh incompatibilitybull Red blood cell defects (G6PD deficiency spherocytosis)bull Rare blood group incompatibilitiesbull Polycythemiabull Sequestered blood (bruising hematoma)bull Infection
III DECREASED CONJUGATION OF BILIRUBIN
bull Prematuritybull Rare inherited defects
IV INCREASED REABSORPTION OF BILIRUBIN FROM THE GI TRACT
bull Asphyxiabull Delayed feedingsbull Bowel obstructionbull Delayed passage of meconium
V IMPAIRMENT OF BILE EXCRETION
bull Sepsisbull Intrauterine infectionsbull Hepatitisbull Cholestatic syndromesbull Biliary atresiabull Cystic fibrosis
VI BREAST MILK JAUNDICE
The association between breastfeeding and higher bilirubin levels is well established however thecause for this has not been determined with certainty6
Jaundice in the Healthy Term Newborn
April 2002 Page 3 of 20
A Early Breastfeeding Jaundice
bull Develops within 2 to 4 days of birthbull Most likely related to infrequent breastfeeding with a limited fluid intakebull May be related to increased reabsorption of bilirubin from the bowel
B Late Breast Milk Jaundice
bull Much less commonbull Develops 4 to 7 days after birth peaks day 7 to 15 bull Cause remains unknown despite numerous theories and studies
STRATEGIES TO DECREASE INCIDENCE
I LABOR AND DELIVERY
bull avoid trauma during labor and delivery8
II BREASTFEEDING
bull provide early assistance education and support for breastfeedingbull ensure parental education regarding signs of adequate hydration signs of jaundice and feeding1 bull initiate early and frequent feedings ndash at least 8 feeds in 24 hours68 Avoid separation of mother
and babybull encourage the ingestion of colostrum to increase stooling which prevents reabsorption of bilirubinbull supplementation with water does not affect bilirubin levels and is not recommended If
supplementation is necessary due to inadequate intake the mother should pump her breasts andgive expressed breastmilk andor formula rather than water
III DISCHARGEFOLLOW-UP
bull ensure adherence to evidence-based and current postpartum discharge criteria9
bull initiate early postpartum follow-up once discharged from hospital All infants discharged prior to48 hours of age should be evaluated by a health care professional within 48 hours after discharge69
bull ensure community mechanisms for follow-up and referral between health care providers (Seeexample in Appendix 1 Management of Newborn Jaundice at Home Program)
SCREENING
I TRANSCUTANEOUS
Use of an icterometer or transcutaneous jaundice meter is sometimes used as a screening device inhealthy term infants810 Accuracy may be limited by the changing pigmentation of the skin theduration of jaundice and the effect of phototherapy11
Jaundice in the Healthy Term Newborn
April 2002
II BILIRUBIN MEASUREMENT
Several studies have looked at the predictive ability of predischarge serum bilirubin testing121314 Todate routine bilirubin investigation for healthy term newborns is not indicated However if theinfantrsquos level of jaundice is a concern at discharge it may be prudent and helpful to obtain a bilirubinlevel at the time that the PKU specimen is collected Reference to the Bhutani Graph (Appendix 3page 17) may then help to determine whether further bilirubin levels should be obtained
ASSESSMENT
I COLOUR
Kramer15 described the cephalocaudal progression of jaundice in term infants He drew attention tothe observation that jaundice starts on the head and extends towards the feet as the level rises This isuseful in deciding whether or not a baby needs to have the serum bilirubin (SBR) measured Kramerdivided the infant into 5 zones The SBR range associated with progression to the zones is as follows
Zone 1 2 3 4 5SBR
(umolL)100 150 200 250 gt250
Adapted from the Department of Neonatal Medicine Protocol Book Royal Prince Alfred Hospital University of Sydney Australia 199816
The colour of the skin should be evaluated after the skin has been blanched by pressure from the thumb in a well lit room (or natural daylight if in the home)
II AGE
Jaundice before 24 hours of age is always pathological
III FEEDING BEHAVIOUR
bull as bilirubin levels rise the baby may become more lethargicbull after the first 1-2 days of life newborns should breastfeed at lebull if baby is sleepy during feeds utilize waking techniques
IV HYDRATION
Adequate intake can be determined by the babyrsquos bull Skin turgorbull Moistness of mouthbull Weightbull Energy levelsbull Feeding patternbehavior
Page 4 of 20
ast 8 times in 24 hours
Jaundice in the Healthy Term Newborn
April 2002 Page 5 of 20
bull Elimination (See guide below)
Guide for Healthy Term Newborn Output
Day Number of Stools24 hours Number of Wet diapers24 hours
1 at least one meconium at least 1 2 at least one meconium at least 2 3 at least 1 transitional at least 3 4 at least 2 + yellowseedy at least 4 5 at least 2 + yellowseedy 5 - 6
See BCRCP British Columbia Newborn Care Path Outcomes Teaching amp Interventions document for norms27
V OTHER ILLNESS
In association with other findings jaundice may be a sign of serious illness Each jaundiced infantshould be assessed to see whether the following danger signs are present
bull Family history of significant hemolytic diseasebull Onset of jaundice within 24 hoursbull Pallor bruising petechiaebull Lethargybull Poor feedingbull Feverbull Vomitingbull Dark urine and light stoolsbull Hepatosplenomegalybull High pitched cry
CLINICAL MANAGEMENT
Clinical management is aimed at avoiding bilirubin encephalopathy with itrsquos long term neurologicalcomplications Adequate hydration is an important consideration in the infant with moderate to highbilirubin levels
Fundamental to management is a good history and physical examination together with appropriateinvestigations including
bull Unconjugated and conjugated bilirubinbull Blood group determination with a direct antibody test (Coombrsquos test)bull Hemoglobin and hematocritbull Other lab investigations (eg T4 G6PD) may be required depending on the patient assessment1
Once the serum bilirubin reaches ldquoriskrdquo levels11217 the standard treatment is the use of phototherapyandor exchange transfusion Several expert bodies have developed guidelines to assist care providers
Jaundice in the Healthy Term Newborn
April 2002 Page 6 of 20
determine the appropriate time to implement each therapy as well as how to provide the therapy mosteffectively11217
The most common guidelines utilized in risk identification and management of hyperbilirubinemia arelisted below
Appendix 2 Approach to the management of hyperbilirubinemia in term newborn infants1 A Joint Statement Canadian Paediatric Society amp College of Family
Physicians of Canada (February 2001) Appendix 3 Hyperbilirubinembia risk designation for term and near-term well newborns12 Bhutani at al (1999) Pediatrics Vol 103 No 1 p6-12
Appendix 4 Management of hyperbilirubinemia in healthy term newborns17 American Academy of Pediatrics (1994)
OTHER ISSUES IN THE MANAGEMENT OF JAUNDICE
I BREASTFEEDING AND PHOTOTHERAPY
bull Interruption of breastfeeding is usually not indicated6bull An adequate intake of milk minimizes the bilirubin level by stimulating bowel emptying
Encourage frequent and effective breastfeeding (as least 8X in 24 hours)618
bull Breastfeeding may be interrupted for diagnostic or therapeutic purposes when the bilirubin is highand there is the risk of an exchange transfusion Should this occurbull continue phototherapybull consider discontinuing breastfeeding for 24 hours or bull alternate breastfeeding with formula feeding if fluid intake is of concernbull offer positive support for breastfeeding Encourage maintenance of lactation by using a breast
pump or manual expression during the period of interrupted breastfeeding6bull Glucose water will not reduce serum bilirubin levels and may interfere with breastfeeding6 II DAYLIGHT TREATMENT
Exposing infants to indirect sunlight via a window to decrease bilirubin levels has been a longstanding practice19 Controlled studies on this treatment have not been done Mild jaundice requiresno sunlight exposure as it sends a false note to parents that their baby has a significant problem whenin fact (s)he has not If an infant has jaundice that needs treatment according to accepted guidelinesthen it should be investigated further
III FIBROPTIC PHOTOTHERAPY
Use of fibroptic or ldquobili blanketsrdquo is gaining increased interest A Cochrane Database Review20 foundthat fibroptic phototherapy was more effective at lowering serum bilirubin than no treatment but less
Jaundice in the Healthy Term Newborn
April 2002 Page 7 of 20
effective than conventional phototherapy A combination of fibroptic and conventional phototherapywas more effective than conventional phototherapy alone No conclusion could be made on thesuperiority of one fibroptic device over another No trials have been identified which support the viewthat fibroptic devices interfere less with infant care or impact less on parent-child bonding
At this time ldquobili blanketsrdquo should not be used alone to treat non-physiologic causes of jaundice orthose infants at risk of requiring an exchange transfusion
IV HOME PHOTOTHERAPY
There are few articles in the literature which address this issue21-24 With the advent of fibropticblankets and portable bilibeds home phototherapy has been implemented in a few communitiesthroughout Canada25-27 To date there are no published evidence-based guidelines on the use of homephototherapy
CLINICAL INDICATORS FOR EVALUATION
bull Serum bilirubin levels at which phototherapy is initiated (age specific in hours of life) bull Bilirubin levels at which the infant is readmitted bull Numbers of readmissions for jaundice
REFERENCES
1 Canadian Paediatric Society amp the College of Family Physicians of Canada (1999) Approach tothe management of hyperbilirubinemia in term newborn infants Paediatrics and Child Health 4(2)161-164 Access from wwwcpscaenglishstatementsFNfn98-02htm
2 Maisels J amp Newman T (1998) Jaundice in full-term and near-term babies who leave thehospital within 36 hours Clinics in Perinatology 25(2) 295-302
3 Maisels J amp Kring E (1998) Length of stay jaundice and hospital readmission Pediatrics101(6) 995-998
4 Gurpp-Phelan J Taylor J Liu L amp Davis R (1999) Early newborn hospital discharge andreadmission for mild and severe jaundice Archive of Pediatric and Adolescent Medicine 153 1283-1288)
5 Liu S Wen S McMillan D Trouton K Fowler D amp McCourt C (2000) Increasedneonatal readmission rate associated with decreased length of hospital stay at birth in CanadaCanadian Journal of Public Health 91(1) 46-50
6 American Academy of Pediatrics amp American College of Obstetricians and Gynecologists(1997) Guidelines for Perinatal Care (4rd Edition) American College of Obstetricians andGynecologists Elk Grove Village IL American Academy of Pediatrics Washington DC
7 Banks J Montgomer D Coody D amp Yetman R (1996) Hyperbilirubinemia in the termnewborn Journal of Pediatric Health Care 10(5) 228-230
Jaundice in the Healthy Term Newborn
April 2002 Page 8 of 20
8 Blackburn S (1995) Hyperbilirubinemia and neonatal jaundice Neonatal Network 14 (7)15-24
9 Canadian Paediatric Society amp the Society of Obstetricians and Gynaecologists of Canada (1996)Joint Policy Statement Facilitating discharge home following a normal term birth Paediatric amp ChildHealth1(2) 165-168Access from httpwwwcpscaenglishstatementsFNfn96-02htm
10 Bhutani V Gourley G Adler S Kreamer B Dalin C Johnson L (2000) NoninvasiveMeasurement of Total Bilirubin in a Multiracial Predischarge Newborn Population to Assess the Riskof Severe Hyperbilirubinemia Pediatrics (106) NO 2 Part 1 of 3
11 Schwoebel A amp Sakraida (1997) Hyperbilirubinemia New approaches to an old problemJournal of Perinatal and Neonatal Nursing 11(3) 78-97
12 Bhutani V Johnson L amp Sivieri E (1999) Predictive ability of a predischarge hour-specificserum bilirubin for subsequent significant hyperbilirubinemia in healthy term and near-term newbornsPediatrics 103(1) 6-14
13 Seidman D Ergaz Z Paz I Laor A Revel-Vilk S Stevenson D amp Gale R (1999)Predicting the risk of jaundice in fullterm healthy newborns A prospective population-based studyJournal of Perinatology 19(8) 564-567
14 Alpay F Sarici U Tosuncuk D Serdar M Inanc N amp Gokcay E (2000) The value offirst-day bilirubin measurement in predicting the development of significant hyperbilirubinemia inhealth term newborns Pediatrics 106(2)
15 Kramer L 1969 Advancement of dermal icterus in the jaundiced newborn American Journal ofDiseases in Children 118 454-458
16 Royal Prince Alfred Hospital 1998 The department of neonatal medicine protocol bookjaundice Sydney Author Accessed May 2001 fromwwwcsnswgovaurpaneonatalhtmlnewprotjaund2htm
17 American Academy of Pediatrics (1994) Practice parameter Management ofhyperbilirubinemia in the healthy term newborn Pediatrics 94(4) 558-565) httpwwwaaporgpolicyhyperbhtm
18 International Lactation Consultant Association (1999) Evidence-Based Guidelines forBreastfeeding Management During the First Fourteen Days Raleigh NC Author
19 Mohrbacher N amp Stock J (1997) The Breastfeeding Answer Book Illinois La Leche League
20 Mills J amp Tudehope D (2001) The Cochrane Database of Systemic Reviews Fibreopticphototherapy for neonatal jaundice Volume (Issue 1)
21 Ludwig M (1990) Phototherapy in the home setting Journal of Pediatric Health Care 4(6)304-308
Jaundice in the Healthy Term Newborn
April 2002 Page 9 of 20
22 Hamelin K amp Seshia M (1998) Home phototherapy for uncomplicated neonatal jaundiceCanadian Nurse Jan 39-40
23 Murphy B amp Welch R (1992) Home phototherapy for the jaundiced full-term newbornJournal of Home Health Care Practitioner 5(1) 26-33
24 British Columbia Reproductive Care Program (2001) British Columbia Newborn Care PathOutcomes Teaching amp Interventions Vancouver Author
25 Campbell River Hospital (2000) Protocol Hyperbilirubinemia ndash Home PhototherapyManagement Campbell River BC Author
26 Mississauga Hospital (1994) Protocol Home Phototherapy Programme Mississauga ONAuthor
27 University of Manitoba Health Science Centre () Protocol Home Phototherapy ProgramWinnepeg Author Access from httpwwwumanitobacawomens_healthhschomethtm
WEB RESOURCES
httpwwwaaporgpolicyhyperbhtm
wwwcpscaenglishstatementsFNfn98-02htm
httpwwwcpscaenglishstatementsFNfn96-02htm
wwwcsnswgovaurpaneonatalhtmlnewprotjaund2htm
httpwwwumanitobacawomens_healthhschomethtm
Jaundice in the Healthy Term Newborn
April 2002 Page 10 of 20
Management of Newborn Jaundice at Home Program
Referral for the Healthy Term Infant
PHN Identifies jaundice in the newborn
1 Preterm Infant RhABO incompatibility2 Look or act ill (eg lethargic apnea tachycardia
temperature unstable poor feeding changed behaviorpersistant vomiting insufficient voidingstooling)
No
Family hx of early or severejaundice Ethnicity relevant(Mediterranean SE Asian)
No
Infant less than24 hrs
No
Is jaundiceclinically
significant
No
Jaundice persistedgt 2 weeks
Jaundice gt3weeks
Routinecare and
feedsNo
Routinecare and
feedsNo
RoutineClinical
Supervis-ion
No
Refer to MD ASAPYes
Refer to MD forinvestigationeg
G6PD SpherocytosisYes
Refer to MD fornon - isoimmune
hemolyticdisease
investigation
Yes
Refer to MD forfollow-up with total
serum bilirubinYes
Any abnormal physicalfindings Dark urine
light stoolsRefer to MDYes Yes
Refer to MDYes
APPENDIX 1 (Example)
Developed by the Coordinated Maternity Standards Committee South FraserHealth Region and Dr K Danso Pediatrician Surrey Memorial Hospital
Revised 1997 Copied with permission
Jaundice in the Healthy Term Newborn
April 2002 Page 11 of 20
APPENDIX 2
Approach to the Management of Hyperbilirubinemiain Term Newborn Infants
A Joint Statement with the College of Family Physicians of CanadaPaediatrics amp Child Health 19994(2)161-164Reference No FN98-02Reaffirmed February 2001
Reprints of this position statement are available from the Canadian Paediatric Society100-2204 Walkley Road Ottawa ON K1G 4G8 phone (613) 526-9397 fax (613) 526-3332
Contents bull Background bull Phototherapy bull Clinical management of hyperbilirubinemia in infants bull Exchange transfusion bull Conclusions bull References
Conflicting reports have led to confusion about the optimal management of jaundice in otherwise healthy terminfants (1-9) The lsquokinder gentler approachrsquo to neonatal hyperbilirubinemia proposed in 1992 by Newman andMaisels (8) resulted in a 1994 statement by the American Academy of Pediatrics (2) that addressed themanagement of healthy term infant without risk factors Recently there has been an increase in the number ofterm infants reported with kernicterus (10) It is important to note that while some of the infants reported withkernicterus had features that would place them in a high risk category some presented with severe jaundiceonly and no identifiable risk factors (10) The infants reported were commonly breastfed and frequentlydischarged from hospital very soon after birth (10) Nonetheless the current standards (2) for the managementof hyperbilirubinemia in the healthy term infant have become controversial This document updates information previously published by the Canadian Paediatric Society (1) It provides anoverview of the proposed management of hyperbilirubinemia based on available evidence even thoughrandomized controlled trials are not available to allow a conclusive assessment of the risk associated withhyperbilirubinemia in the clinical situations encountered in practice The objective of this overview is toestablish a management plan that will minimize the risk of kernicterus in term infants both with and withoutrisk factors Although scientific evidence has not established a clear link between specific bilirubinconcentrations and the development of kernicterus in healthy term babies information to date has beenincorporated into the following guidelines Background
Kernicterus is a neurological condition characterized by deep yellow staining of the basal nuclei Theaccompanying clinical syndrome results from the destructive changes of these neuronal populations Initiallythe signs are lethargy hypotonia and seizures later the infants may develop athetoid cerebral palsy mentalretardation and deafness When neurological signs evident in the infant permanent damage has alreadyoccurred leading to death or long term disability Therefore management strategies are aimed at preventingkernicterus
Jaundice in the Healthy Term Newborn
April 2002 Page 12 of 20
Until recently these strategies suggested maintaining serum unconjugated bilirubin concentrations below 340micromolL (20 mgdL) in healthy term infants through the use of phototherapy or exchange transfusion (11) Whileexchange transfusions had been a frequent occurrence from the 1950s to the 1970s and may sometimes still berequired phototherapy has become the mainstay of medical management of hyperbilirubinemia since that time
The cases of kernicterus originally described occurred mainly in infants with hemolytic disease Higher serumunconjugated bilirubin concentrations may be safe in healthy term infants without hemolytic disease It is notpossible to predict at what level an individual infant may develop kernicterus
Several authors have expressed serious concerns over the approach of allowing higher serum unconjugatedbilirubin concentrations to occur before investigating and treating these term infants (11-16) Brown andJohnson (10) have reported 23 cases of kernicterus occurring since 1989 16 in term and seven in near terminfants In these infants peak unconjugated bilirubin concentrations of 375 to 860 micromolL (22 to 50 mgdL)were seen All but one infant was breastfed Other associations found in these infants with kernicterus weredehydration (seven infants) glucose-6-phosphate dehydrogenase (G6PD) deficiency (five infants) ABOalloimmunization (one infant) hemolysis of unknown cause (five infants) familial etiology (one infant) andotherwise unexplained early jaundice clinically evident before 24 h of age (six infants) Similar cases have beenreported by others (1718) Although many of these babies were subsequently found to have additional riskfactors these factors were not often identified at the time the baby was noted to be jaundiced
Since the introduction in the 1990s of the kinder gentler approach to the management of hyperbilirubinemia agreat deal of confusion has arisen about approaches to the management of hyperbilirubinemia in healthy terminfants This confusion has extended to the care of borderline preterm infants who have often been treated asterm infants A recently published international survey reported considerable variability in the approach tohyperbilirubinemia and the use of phototherapy among neonatal units worldwide (3)
PhototherapyThe goal of hyperbilirubinemia treatment is to avoid bilirubin concentrations that may result in kernicterusPhototherapy remains an effective therapeutic intervention that decreases bilirubin concentrations therebypreventing elevated bilirubin levels associated with permanent sequelae
The effectiveness of phototherapy is related to the area of skin exposed and the radiant energy and thewavelength of the light (19-23) Phototherapy acts on unconjugated bilirubin to a depth of 2 mm from theepidermis Phototherapy changes the bilirubin through structural photoisomerization into water-solublelumirubin that is excreted in the urine (19) The fall in bilirubin level is proportionately greater in the skin thanin the serum (20) Therefore the infant receiving phototherapy should have as much skin as possible exposed tothe lights More intense phototherapy may be achieved by using multiple sources of phototherapy double ortriple phototherapy is recommended to optimize the skin surface exposed and therefore the efficacy ofphototherapy More detailed discussion of the physics of phototherapy has been published (124) It is important to recognize the relationship between dehydration and hyperbilirubinemia Dehydration may beassociated with increased serum bilirubin concentrations and may be exacerbated by phototherapy Alljaundiced infants should be adequately hydrated before and during phototherapy Breastfeeding is notcontraindicated in the presence of hyperbilirubinemia and should be continued More frequent breastfeedingsmay be beneficial (25)
The concentrations of bilirubin at which phototherapy might be initiated in healthy term infants and those withrisk factors are shown in Figure 1 Guidelines for phototherapy in low birth weight infants remain as previouslypublished (1) The bilirubin concentrations at which phototherapy is suggested by the Canadian PaediatricSociety in the present statement are more conservative than the current recommendations of the AmericanAcademy of Pediatrics (2) If the infant is a healthy term newborn phototherapy should be started as indicated
Jaundice in the Healthy Term Newborn
April 2002 Page 13 of 20
in the upper curve of Figure 1 If the infant has one or more risk factors a clinical decision should be made toinitiate phototherapy at the concentration indicated by the lower curve
Figure 1 Guidelines for initiation of phototherapy for hyperbilirubinemia in term infants with and without riskfactors Some risk factors include gestional age younger than 37 weeks birth weight less than 2500 ghemolysis jaundice at younger than 24 h of age sepsis and the need for resuscitation at birth
The timely recognition of risk factors is essential to minimize the danger of kernicterus The risk factors are asfollows
bull gestational age younger than 37 weeks and birth weight less than 2500 g bull hemolysis due to maternal isoimmunization G6PD deficiency spherocytosis or other causes bull jaundice at less than 24 h of age bull sepsis and bull the need for resuscitation at birth
Jaundice in the Healthy Term Newborn
April 2002 Page 14 of 20
Clinical management of hyperbilirubinemia in infants
A bilirubin level that justifies consideration of phototherapy should mandate the investigation of the cause ofhyperbilirubinemia Investigation should include a clinically pertinent history of the mother family historydescription of labour and delivery and infantrsquos clinical course (26) A physical examination should besupplemented by laboratory investigations (Table 1) including determination of unconjugated and conjugatedserum bilirubin concentrations and blood group with direct antibody test (Coombsrsquo test) and hemoglobin andhematocrit levels A complete blood count including differential white cell count and a blood smear for red cellmorphology may be indicated Further tests (eg reticulocyte count G6PD screen) may be indicated based oninitial results ethnicity or clinical presentation Testing for serum electrolytes and albumin or protein areindicated in some situations such as suspected dehydration or when bilirubin levels approach exchange valuesIn the absence of drugs or clinical states that alter the binding of bilirubin by albumin the bilirubin to albuminor the bilirubin to protein ratio reflects the free bilirubin concentration and the binding capacity of the serum(27-29) At a bilirubin concentration close to exchange transfusion levels some clinicians may wish to ensurethat serum bilirubin binding is normal (albumin 25 gL or greater protein 54 gL or greater) Values belowthese levels may be associated with low bilirubin binding and may be used by the clinician when decidingwhether further intervention (eg exchange transfusion) should take place (27)
TABLE 1 Laboratory investigation for hyperbilirubinemia in term newborn infants
Indicated (if bilirubin concentrations reach phototherapy levels) Serum total or unconjugated bilirubin concentration Serum conjugated bilirubin concentration Blood group with direct antibody test (Coombsrsquo test) Hemoglobin and hematocrit determinations
Optional (in specific clinical circumstances) Complete blood count including manual differential white cell count Blood smear for red cell morphology Reticulocyte count Glucose-6-phosphate dehydrogenase screen Serum electrolytes and albumin or protein concentrations
For infants with prolonged jaundice (lasting longer than seven days) or with conjugated hyperbilirubinemia(greater than 30 micromolL) additional investigation and management may be required and a consultation with aspecialist may be needed (30)
During the past decade most nurseries have shortened the time of hospital stay for term healthy newborninfants Early discharge of neonates means that jaundice is not often recognized at discharge (31) The CanadianPaediatric Society reiterates the importance of allowing early discharge only if a healthy status is confirmed foreach baby and appropriate follow-up is provided (32) Appropriate parental education about feeding signs ofdehydration and jaundice must be implemented in hospital nurseries Testing for serum bilirubin concentrationsmust be readily available for newborns on an out-patient basis Readmission to hospital (usually the hospital ofbirth) may be necessary for the investigation and management of hyperbilirubinemia
Exchange transfusion If phototherapy fails to control the rising bilirubin levels exchange transfusion is indicated to lower serumbilirubin concentrations For healthy term infants without risk factors exchange transfusion should beconsidered at serum unconjugated bilirubin concentrations of 400 to 430 micromolL For term infants with riskfactors the level should be 340 micromolL For infants who initially present with serum bilirubin concentrations in
Jaundice in the Healthy Term Newborn
April 2002 Page 15 of 20
excess of exchange levels intensive phototherapy should produce a decline of serum unconjugated bilirubinfrom 20 to 35 micromolL within 4 to 6 h and levels should continue to fall thereafter and remain below thethreshold for exchange transfusion If the bilirubin concentration does not decrease after adequate rehydrationand 4 to 6 h of intensive phototherapy exchange transfusion should be considered Preparation for thisincluding ensuring availability of blood should occur shortly after the admission of babies whose bilirubinconcentrations exceed exchange levels Appropriate consultation should be obtained if the etiology ofhyperbilirubinemia is unclear the infant is ill and particularly if bilirubin concentrations are approachingexchange levels Because the risks of exchange transfusion are significant the best management may bereviewed with an expert opinion from a neonatologist
Conclusions Hyperbilirubinemia in apparently healthy term newborn infants continues to hold the potential threat ofcomplications from bilirubin encephalopathy and kernicterus Careful assessment of risk factors judicious useof phototherapy appropriate laboratory monitoring and specific treatment of other disorders (eg sepsis) areessential for the optimal management of hyperbilirubinemia Appropriate laboratory facilities must be availableto measure bilirubin concentrations for out-patients in required clinical situations Readmission to hospital maybe required if phototherapy is necessary Guidelines for phototherapy are presented for term babies with andwithout identifiable risk factors
References
1 Fetus and Newborn Committee Canadian Paediatric Society Use of phototherapy for neonatalhyperbilirubinemia Can Med Assoc J 19861341237-45 2 American Academy of Pediatrics Practice parameter Management of hyperbilirubinemia in the healthy termnewborn Pediatrics 199494558-65 3 Hansen TWR Therapeutical approaches to neonatal jaundice an international survey Clin Pediatr199635309-16 4 Valaes T Koliopoulos C Koltsidopoulos A The impact of phototherapy in the management of neonatalhyperbilirubinemia comparison of historical cohorts Acta Paediatrica 199685273-6 5 Gustafson PA Boyle DW Bilirubin index a new standard for intervention Med Hypotheses 199545409-16 6 Torres-Torres M Tayaba R Weintraub A Holzman IR New perspectives on neonatal hyperbilirubinemiaMount Sinai J Med 199461424-8 7 Lazar L Litwin A Merlob P Phototherapy for neonatal nonhemolytic hyperbilirubinemia analysis ofrebound and indications for discontinuing therapy Clin Pediatr 199332264-7 8 Newman TB Maisels MJ Evaluation and treatment of jaundice in the term newborn Pediatrics 199289809-18 9 McMillan DD Lockyer JM Magnan L Akierman A Parboosingh JT Effect of educational program andinterview on adoption of guidelines for the management of neonatal hyperbilirubinemia Can Med Assoc J1991144707-12 10 Brown AK Johnson L Loss of concern about jaundice and the reemergence of kernicterus in full-terminfants in the era of managed care In Fanaroff AA Klaus MH eds The Year Book of Neonatal and PerinatalMedicine Philadelphia Mosby Yearbook 199617-28 11 Valaes T Bilirubin toxicity The problem was solved a generation ago Pediatrics 199289819-21 12 Wennberg RP Bilirubin recommendations present problems New guidelines simplistic and untestedPediatrics 199289821-2 13 Merenstein GB lsquoNewrsquo bilirubin recommendations questioned Pediatrics 199289822-3 14 Poland RL In search of a lsquogold standardrsquo for bilirubin toxicity Pediatrics 199289823-4 15 Brown AK Seidman DS Stevenson DK Jaundice in healthy term neonates Do we need new action levelsor new approaches Pediatrics 199289827-9 16 Johnson L Yet another expert opinion on bilirubin toxicity Pediatrics 199289829-31
Jaundice in the Healthy Term Newborn
April 2002 Page 16 of 20
17 MacDonald MG Hidden risks Early discharge and bilirubin toxicity due to glucose-6-phosphatedehydrogenase deficiency Pediatrics 199596734-8 18 Maisels MJ Newman TB Kernicterus in otherwise healthy breast-fed newborns Pediatrics 199596730-3 19 Vogl TP Phototherapy of neonatal hyperbilirubinemia bilirubin in unexposed areas of the skin J Pediatr197485707-1020 Rubaltelli FF Carli M The effect of light on cutaneous bilirubin Biol Neonate 197118457-62 21 Sisson TR Kendall N Shaw E et al Phototherapy of jaundice in the newborn infant 2 Effect of variouslight intensities J Pediatr 19738135-8 22 Bonta BW Warshaw JB Importance of radiant flux in the treatment of hyperbilirubinemia failure ofoverhead phototherapy units in intensive care units Pediatrics 197657502-5 23 Warshaw JB Gagliardi J Patel A A comparison of fluorescent and non-fluorescent light source forphototherapy Pediatrics 198065795-8 24 Ennever JF Blue light green light white light more light treatment of neonatal jaundice Clin Perinatol199017467-8125 Auerbach KG Gartner LM Breastfeeding and human milk their association with jaundice in the neonateClin Perinatol 19871489-108 26 Maisels MJ Jaundice in the newborn Pediatr Rev 19823305-20 27 Ahlfors CE Criteria for exchange transfusion in jaundiced newborns Pediatrics 199493488-94 28 Odell GB Storey GNB Rosenberg LA Studies in kernicterus III The saturation of serum protein withbilirubin during neonatal life and its relationship to brain damage at 5 years J Pediatr 19707612-21 29 Wirth FH Goldberg KE Lubchenco LO The neurologic outcome of infants evaluated for unboundbilirubin Pediatr Res 19759385-91 30 Haber BA Lake AM Cholestatic jaundice in the newborn Clin Perinatol 199017483-506 31 Maisels MJ Newman TB Jaundice in full-term and near-term babies who leave the hospital within 36hours The pediatricianrsquos nemesis Clin Perinatol 199825295-302 32 Fetus and Newborn Committee Canadian Paediatric Society and Society of Obstetricians andGynaecologists of Canada Facilitating discharge home following a normal term birth Paediatr Child Health19961165-8
Fetus and Newborn Committee Members Drs John Watts Department of Paediatrics Childrenrsquos Hospital ndash Hamilton Health Sciences CentreHamilton Ontario (director responsible) Douglas McMillan Department of Pediatrics Foothills HospitalCalgary Alberta (chair) Arne Ohlsson Department of Paediatrics Mount Sinai Hospital Toronto Ontario(co-chair) Deborah Davis Childrenrsquos Hospital of Eastern Ontario Ottawa Ontario Daniel Faucher RoyalVictoria Hospital Montreal Quebec (principal author) John Van Aerde Stollery Childrenrsquos Health CentreEdmonton Alberta Michael Vincer IWK-Grace Health Centre Halifax Nova ScotiaConsultant Dr Michael C Klein University of British Columbia Vancouver British Columbia (College ofFamily Physicians of Canada)Liaisons Drs James Lemon Riley Childrenrsquos Hospital Indiana University Medical Center IndianapolisIndiana (American Academy of Pediatrics) Saroj Saigal Department of Paediatrics McMaster UniversityMedical Centre Childrenrsquos Hospital ndash Hamilton Health Sciences Centre Hamilton Ontario (CPS Neonatal-Perinatal Medicine Section) Cheryl Levitt Department of Family Medicine Childrenrsquos Hospital ndash HamiltonHealth Sciences Centre Hamilton Ontario (College of Family Physicians of Canada) Catherine McCourtDirector Bureau of Reproductive amp Child Health Laboratory Centre for Disease Control Ottawa Ontario(Health Canada) Mrs Debbie Fraser-Askin Winnipeg Manitoba (Neonatal Nurses) Dr Line LeducDepartment of Obstetrics-Gynecology Hocircpital Sainte-Justine Montreal Quebec (Society of Obstetricians andGynaecologists of Canada)
Disclaimer The recommendations in this position statement do not indicate an exclusive course oftreatment or procedure to be followed Variations taking into account individual circumstances may beappropriate
Jaundice in the Healthy Term Newborn
April 2002 Page 17 of 20
APPENDIX 3Hyperbilirubinemia Risk Designation for Term and Near-Term Well Newborns
Jaundice in the Healthy Term Newborn
April 2002 Page 18 of 20
APPENDIX 4
American Academy of Pediatrics 1994 Practice parameter Management ofHyperbilirubinemia in the Healthy Term Newborn Pediatrics 94(4) 558-565
(Chart and Algorithm)
Jaundice in the Healthy Term Newborn
April 2002 Page 19 of 20
AlgorithmPediatric clinician evaluatesterm newborn with jaundice
Does the infant have signs of underlyingserious illness (lethargy apnea tachypneatemperature instability behavior changeshepatosplenomegaly persistant vomiting
or persistent feeding difficulty)
1
2
Exit this algorithm to individualizedclinical evaluation including
assessment of jaundice and underlyingdisease
Yes
3
No
Is the infant lt 37 weeks gestational age
4 Exit this algorithm to individualizedclinical evaluation including
assessment of jaundice in light ofprematurity
5
Yes
Is the mothersABO and Rh
blood typing andisoimmune
antibody screenstatus known
Is the mothersblood Rhpositive
Does themothers blood
have anyimmune
antibodies
Consider holding the infantscord blood in the blood bank incase future testing is necessary
6 7 8 9No
Yes Yes No
(Go to Box 10) (Go to Box 10) (Go to Box 10) (Go to Box 13)
No No Yes
Perform blood typing (ABO and Rh) and direct Coombs testingon the infants cord (preferably) or venous blood
10
Is the infantsblood direct
Coombs testpositive
Exit this algorithm to individualized clinical evaluationincluding assessment of jaundice and isoimmune
hemolytic disease
11 12
Yes
Are any of the following risk factors present tosuggest that nonisoimmune hemolytic disease
is possible in this infant(1) Family history of hemolytic anemia
OR(2) Family history of early or severe jaundice
OR(3) Ethnicity or geographic originassociated with hemolytic anemia
OR(4) Early or severe jaundice
Perform appropriate laboratoryassessment of infant including
(but not limited to consideration of)(1) Complete blood count differentialsmear reticulocyte count(2) G6PD screen(3) Hemoglobin electrophoresis
1314
No
No
No
(Go to Box 16)
Does the evaluation suggesthemolytic disease
15
Yes
(Go to Box 17)(Go to Box 16)
No
Jaundice in the Healthy Term Newborn
April 2002 Page 20 of 20
AlgorithmIs the infant
jaundiced andlt 24 hours of
age
Exit this algorithm to individualizedclinical evaluation includingassessment of jaundice and
nonisoimmune hemolytic disease
Is jaundiceclinicallysignificant by medical
judgment
(1) Measure infantstotal serum bilirubin(2) Go to Box 27
Healthy term infant with jaundice not clinicallysignificant by medical judgment
Follow infant in routine clinical supervision
1617
18 19
20
21
(Go to Box 22)
Yes
Yes
No
No
Is jaundicepersisting
gt 2 weeks
Does this infant haveabnormal physicalexam results dark
urine or light stools
Is jaundice persistinggt 3 weeks
Perform appropriate physical andlaboratory assessment of theinfant including possibility of
cholestatic jaundice
Provide routine carerecommend routine
feeding and follow-up Table 2 Management of Hyperbilirubinemia in the Healthy Term NewbornAgehours TSB Level mgdL (umolL)
Consider Phototherapy Exchange ExchangePhototherapy Transfusion Transfusion
if Intensive and IntensivePhototherapy PhototherapyFails
lt24 25-48 gt 12 (170) gt15 (260) gt 20 (340) gt 25 (430)49-72 gt 15 (260) gt 18 (310) gt 25 (430) gt 30 (510)gt 72 gt 17 (290) gt 20 (340) gt 25 (430) gt 30 (510)
TSB indicates total serum bilirubinPhototherapy at these TSB levels is a clinical option meaning that the intervention is availableand may be used on the basis of individual clinical judgement For a more detailed descriptionof phototherapy see the AppendixIntensive phototherapy (Appendix) should produce a decline of TSB of 1 to 2 mgdL within 4 to 6hours and the TSB level should continue to fall and remain below the threshold level for exchangetransfusion If this does not occur it is considered a failure of phototherapyTerm infants who are clinically jaundiced at lt 24 hours old are not considered healthy andrequire further evaluation (see text)
22 23
24
25
26
YesYes
No
YesNo
No 27
Algorithm Management of hyperbilirubinemia inthe healthy term infant
(From Box 19)
Jaundice in the Healthy Term Newborn
April 2002 Page 2 of 20
CAUSES
I PHYSIOLOGIC JAUNDICE
Increased bilirubin load due to
bull Increased red blood cell volumebull Immaturity of bilirubin conjugation in the liver at birthbull Increased enterohepatic circulation of bilirubinbull Decreased red blood cell survivalbull Decreased uptake of bilirubin from the plasma by the liver
II INCREASED BREAKDOWN OF RED BLOOD CELLS
bull Blood group and Rh incompatibilitybull Red blood cell defects (G6PD deficiency spherocytosis)bull Rare blood group incompatibilitiesbull Polycythemiabull Sequestered blood (bruising hematoma)bull Infection
III DECREASED CONJUGATION OF BILIRUBIN
bull Prematuritybull Rare inherited defects
IV INCREASED REABSORPTION OF BILIRUBIN FROM THE GI TRACT
bull Asphyxiabull Delayed feedingsbull Bowel obstructionbull Delayed passage of meconium
V IMPAIRMENT OF BILE EXCRETION
bull Sepsisbull Intrauterine infectionsbull Hepatitisbull Cholestatic syndromesbull Biliary atresiabull Cystic fibrosis
VI BREAST MILK JAUNDICE
The association between breastfeeding and higher bilirubin levels is well established however thecause for this has not been determined with certainty6
Jaundice in the Healthy Term Newborn
April 2002 Page 3 of 20
A Early Breastfeeding Jaundice
bull Develops within 2 to 4 days of birthbull Most likely related to infrequent breastfeeding with a limited fluid intakebull May be related to increased reabsorption of bilirubin from the bowel
B Late Breast Milk Jaundice
bull Much less commonbull Develops 4 to 7 days after birth peaks day 7 to 15 bull Cause remains unknown despite numerous theories and studies
STRATEGIES TO DECREASE INCIDENCE
I LABOR AND DELIVERY
bull avoid trauma during labor and delivery8
II BREASTFEEDING
bull provide early assistance education and support for breastfeedingbull ensure parental education regarding signs of adequate hydration signs of jaundice and feeding1 bull initiate early and frequent feedings ndash at least 8 feeds in 24 hours68 Avoid separation of mother
and babybull encourage the ingestion of colostrum to increase stooling which prevents reabsorption of bilirubinbull supplementation with water does not affect bilirubin levels and is not recommended If
supplementation is necessary due to inadequate intake the mother should pump her breasts andgive expressed breastmilk andor formula rather than water
III DISCHARGEFOLLOW-UP
bull ensure adherence to evidence-based and current postpartum discharge criteria9
bull initiate early postpartum follow-up once discharged from hospital All infants discharged prior to48 hours of age should be evaluated by a health care professional within 48 hours after discharge69
bull ensure community mechanisms for follow-up and referral between health care providers (Seeexample in Appendix 1 Management of Newborn Jaundice at Home Program)
SCREENING
I TRANSCUTANEOUS
Use of an icterometer or transcutaneous jaundice meter is sometimes used as a screening device inhealthy term infants810 Accuracy may be limited by the changing pigmentation of the skin theduration of jaundice and the effect of phototherapy11
Jaundice in the Healthy Term Newborn
April 2002
II BILIRUBIN MEASUREMENT
Several studies have looked at the predictive ability of predischarge serum bilirubin testing121314 Todate routine bilirubin investigation for healthy term newborns is not indicated However if theinfantrsquos level of jaundice is a concern at discharge it may be prudent and helpful to obtain a bilirubinlevel at the time that the PKU specimen is collected Reference to the Bhutani Graph (Appendix 3page 17) may then help to determine whether further bilirubin levels should be obtained
ASSESSMENT
I COLOUR
Kramer15 described the cephalocaudal progression of jaundice in term infants He drew attention tothe observation that jaundice starts on the head and extends towards the feet as the level rises This isuseful in deciding whether or not a baby needs to have the serum bilirubin (SBR) measured Kramerdivided the infant into 5 zones The SBR range associated with progression to the zones is as follows
Zone 1 2 3 4 5SBR
(umolL)100 150 200 250 gt250
Adapted from the Department of Neonatal Medicine Protocol Book Royal Prince Alfred Hospital University of Sydney Australia 199816
The colour of the skin should be evaluated after the skin has been blanched by pressure from the thumb in a well lit room (or natural daylight if in the home)
II AGE
Jaundice before 24 hours of age is always pathological
III FEEDING BEHAVIOUR
bull as bilirubin levels rise the baby may become more lethargicbull after the first 1-2 days of life newborns should breastfeed at lebull if baby is sleepy during feeds utilize waking techniques
IV HYDRATION
Adequate intake can be determined by the babyrsquos bull Skin turgorbull Moistness of mouthbull Weightbull Energy levelsbull Feeding patternbehavior
Page 4 of 20
ast 8 times in 24 hours
Jaundice in the Healthy Term Newborn
April 2002 Page 5 of 20
bull Elimination (See guide below)
Guide for Healthy Term Newborn Output
Day Number of Stools24 hours Number of Wet diapers24 hours
1 at least one meconium at least 1 2 at least one meconium at least 2 3 at least 1 transitional at least 3 4 at least 2 + yellowseedy at least 4 5 at least 2 + yellowseedy 5 - 6
See BCRCP British Columbia Newborn Care Path Outcomes Teaching amp Interventions document for norms27
V OTHER ILLNESS
In association with other findings jaundice may be a sign of serious illness Each jaundiced infantshould be assessed to see whether the following danger signs are present
bull Family history of significant hemolytic diseasebull Onset of jaundice within 24 hoursbull Pallor bruising petechiaebull Lethargybull Poor feedingbull Feverbull Vomitingbull Dark urine and light stoolsbull Hepatosplenomegalybull High pitched cry
CLINICAL MANAGEMENT
Clinical management is aimed at avoiding bilirubin encephalopathy with itrsquos long term neurologicalcomplications Adequate hydration is an important consideration in the infant with moderate to highbilirubin levels
Fundamental to management is a good history and physical examination together with appropriateinvestigations including
bull Unconjugated and conjugated bilirubinbull Blood group determination with a direct antibody test (Coombrsquos test)bull Hemoglobin and hematocritbull Other lab investigations (eg T4 G6PD) may be required depending on the patient assessment1
Once the serum bilirubin reaches ldquoriskrdquo levels11217 the standard treatment is the use of phototherapyandor exchange transfusion Several expert bodies have developed guidelines to assist care providers
Jaundice in the Healthy Term Newborn
April 2002 Page 6 of 20
determine the appropriate time to implement each therapy as well as how to provide the therapy mosteffectively11217
The most common guidelines utilized in risk identification and management of hyperbilirubinemia arelisted below
Appendix 2 Approach to the management of hyperbilirubinemia in term newborn infants1 A Joint Statement Canadian Paediatric Society amp College of Family
Physicians of Canada (February 2001) Appendix 3 Hyperbilirubinembia risk designation for term and near-term well newborns12 Bhutani at al (1999) Pediatrics Vol 103 No 1 p6-12
Appendix 4 Management of hyperbilirubinemia in healthy term newborns17 American Academy of Pediatrics (1994)
OTHER ISSUES IN THE MANAGEMENT OF JAUNDICE
I BREASTFEEDING AND PHOTOTHERAPY
bull Interruption of breastfeeding is usually not indicated6bull An adequate intake of milk minimizes the bilirubin level by stimulating bowel emptying
Encourage frequent and effective breastfeeding (as least 8X in 24 hours)618
bull Breastfeeding may be interrupted for diagnostic or therapeutic purposes when the bilirubin is highand there is the risk of an exchange transfusion Should this occurbull continue phototherapybull consider discontinuing breastfeeding for 24 hours or bull alternate breastfeeding with formula feeding if fluid intake is of concernbull offer positive support for breastfeeding Encourage maintenance of lactation by using a breast
pump or manual expression during the period of interrupted breastfeeding6bull Glucose water will not reduce serum bilirubin levels and may interfere with breastfeeding6 II DAYLIGHT TREATMENT
Exposing infants to indirect sunlight via a window to decrease bilirubin levels has been a longstanding practice19 Controlled studies on this treatment have not been done Mild jaundice requiresno sunlight exposure as it sends a false note to parents that their baby has a significant problem whenin fact (s)he has not If an infant has jaundice that needs treatment according to accepted guidelinesthen it should be investigated further
III FIBROPTIC PHOTOTHERAPY
Use of fibroptic or ldquobili blanketsrdquo is gaining increased interest A Cochrane Database Review20 foundthat fibroptic phototherapy was more effective at lowering serum bilirubin than no treatment but less
Jaundice in the Healthy Term Newborn
April 2002 Page 7 of 20
effective than conventional phototherapy A combination of fibroptic and conventional phototherapywas more effective than conventional phototherapy alone No conclusion could be made on thesuperiority of one fibroptic device over another No trials have been identified which support the viewthat fibroptic devices interfere less with infant care or impact less on parent-child bonding
At this time ldquobili blanketsrdquo should not be used alone to treat non-physiologic causes of jaundice orthose infants at risk of requiring an exchange transfusion
IV HOME PHOTOTHERAPY
There are few articles in the literature which address this issue21-24 With the advent of fibropticblankets and portable bilibeds home phototherapy has been implemented in a few communitiesthroughout Canada25-27 To date there are no published evidence-based guidelines on the use of homephototherapy
CLINICAL INDICATORS FOR EVALUATION
bull Serum bilirubin levels at which phototherapy is initiated (age specific in hours of life) bull Bilirubin levels at which the infant is readmitted bull Numbers of readmissions for jaundice
REFERENCES
1 Canadian Paediatric Society amp the College of Family Physicians of Canada (1999) Approach tothe management of hyperbilirubinemia in term newborn infants Paediatrics and Child Health 4(2)161-164 Access from wwwcpscaenglishstatementsFNfn98-02htm
2 Maisels J amp Newman T (1998) Jaundice in full-term and near-term babies who leave thehospital within 36 hours Clinics in Perinatology 25(2) 295-302
3 Maisels J amp Kring E (1998) Length of stay jaundice and hospital readmission Pediatrics101(6) 995-998
4 Gurpp-Phelan J Taylor J Liu L amp Davis R (1999) Early newborn hospital discharge andreadmission for mild and severe jaundice Archive of Pediatric and Adolescent Medicine 153 1283-1288)
5 Liu S Wen S McMillan D Trouton K Fowler D amp McCourt C (2000) Increasedneonatal readmission rate associated with decreased length of hospital stay at birth in CanadaCanadian Journal of Public Health 91(1) 46-50
6 American Academy of Pediatrics amp American College of Obstetricians and Gynecologists(1997) Guidelines for Perinatal Care (4rd Edition) American College of Obstetricians andGynecologists Elk Grove Village IL American Academy of Pediatrics Washington DC
7 Banks J Montgomer D Coody D amp Yetman R (1996) Hyperbilirubinemia in the termnewborn Journal of Pediatric Health Care 10(5) 228-230
Jaundice in the Healthy Term Newborn
April 2002 Page 8 of 20
8 Blackburn S (1995) Hyperbilirubinemia and neonatal jaundice Neonatal Network 14 (7)15-24
9 Canadian Paediatric Society amp the Society of Obstetricians and Gynaecologists of Canada (1996)Joint Policy Statement Facilitating discharge home following a normal term birth Paediatric amp ChildHealth1(2) 165-168Access from httpwwwcpscaenglishstatementsFNfn96-02htm
10 Bhutani V Gourley G Adler S Kreamer B Dalin C Johnson L (2000) NoninvasiveMeasurement of Total Bilirubin in a Multiracial Predischarge Newborn Population to Assess the Riskof Severe Hyperbilirubinemia Pediatrics (106) NO 2 Part 1 of 3
11 Schwoebel A amp Sakraida (1997) Hyperbilirubinemia New approaches to an old problemJournal of Perinatal and Neonatal Nursing 11(3) 78-97
12 Bhutani V Johnson L amp Sivieri E (1999) Predictive ability of a predischarge hour-specificserum bilirubin for subsequent significant hyperbilirubinemia in healthy term and near-term newbornsPediatrics 103(1) 6-14
13 Seidman D Ergaz Z Paz I Laor A Revel-Vilk S Stevenson D amp Gale R (1999)Predicting the risk of jaundice in fullterm healthy newborns A prospective population-based studyJournal of Perinatology 19(8) 564-567
14 Alpay F Sarici U Tosuncuk D Serdar M Inanc N amp Gokcay E (2000) The value offirst-day bilirubin measurement in predicting the development of significant hyperbilirubinemia inhealth term newborns Pediatrics 106(2)
15 Kramer L 1969 Advancement of dermal icterus in the jaundiced newborn American Journal ofDiseases in Children 118 454-458
16 Royal Prince Alfred Hospital 1998 The department of neonatal medicine protocol bookjaundice Sydney Author Accessed May 2001 fromwwwcsnswgovaurpaneonatalhtmlnewprotjaund2htm
17 American Academy of Pediatrics (1994) Practice parameter Management ofhyperbilirubinemia in the healthy term newborn Pediatrics 94(4) 558-565) httpwwwaaporgpolicyhyperbhtm
18 International Lactation Consultant Association (1999) Evidence-Based Guidelines forBreastfeeding Management During the First Fourteen Days Raleigh NC Author
19 Mohrbacher N amp Stock J (1997) The Breastfeeding Answer Book Illinois La Leche League
20 Mills J amp Tudehope D (2001) The Cochrane Database of Systemic Reviews Fibreopticphototherapy for neonatal jaundice Volume (Issue 1)
21 Ludwig M (1990) Phototherapy in the home setting Journal of Pediatric Health Care 4(6)304-308
Jaundice in the Healthy Term Newborn
April 2002 Page 9 of 20
22 Hamelin K amp Seshia M (1998) Home phototherapy for uncomplicated neonatal jaundiceCanadian Nurse Jan 39-40
23 Murphy B amp Welch R (1992) Home phototherapy for the jaundiced full-term newbornJournal of Home Health Care Practitioner 5(1) 26-33
24 British Columbia Reproductive Care Program (2001) British Columbia Newborn Care PathOutcomes Teaching amp Interventions Vancouver Author
25 Campbell River Hospital (2000) Protocol Hyperbilirubinemia ndash Home PhototherapyManagement Campbell River BC Author
26 Mississauga Hospital (1994) Protocol Home Phototherapy Programme Mississauga ONAuthor
27 University of Manitoba Health Science Centre () Protocol Home Phototherapy ProgramWinnepeg Author Access from httpwwwumanitobacawomens_healthhschomethtm
WEB RESOURCES
httpwwwaaporgpolicyhyperbhtm
wwwcpscaenglishstatementsFNfn98-02htm
httpwwwcpscaenglishstatementsFNfn96-02htm
wwwcsnswgovaurpaneonatalhtmlnewprotjaund2htm
httpwwwumanitobacawomens_healthhschomethtm
Jaundice in the Healthy Term Newborn
April 2002 Page 10 of 20
Management of Newborn Jaundice at Home Program
Referral for the Healthy Term Infant
PHN Identifies jaundice in the newborn
1 Preterm Infant RhABO incompatibility2 Look or act ill (eg lethargic apnea tachycardia
temperature unstable poor feeding changed behaviorpersistant vomiting insufficient voidingstooling)
No
Family hx of early or severejaundice Ethnicity relevant(Mediterranean SE Asian)
No
Infant less than24 hrs
No
Is jaundiceclinically
significant
No
Jaundice persistedgt 2 weeks
Jaundice gt3weeks
Routinecare and
feedsNo
Routinecare and
feedsNo
RoutineClinical
Supervis-ion
No
Refer to MD ASAPYes
Refer to MD forinvestigationeg
G6PD SpherocytosisYes
Refer to MD fornon - isoimmune
hemolyticdisease
investigation
Yes
Refer to MD forfollow-up with total
serum bilirubinYes
Any abnormal physicalfindings Dark urine
light stoolsRefer to MDYes Yes
Refer to MDYes
APPENDIX 1 (Example)
Developed by the Coordinated Maternity Standards Committee South FraserHealth Region and Dr K Danso Pediatrician Surrey Memorial Hospital
Revised 1997 Copied with permission
Jaundice in the Healthy Term Newborn
April 2002 Page 11 of 20
APPENDIX 2
Approach to the Management of Hyperbilirubinemiain Term Newborn Infants
A Joint Statement with the College of Family Physicians of CanadaPaediatrics amp Child Health 19994(2)161-164Reference No FN98-02Reaffirmed February 2001
Reprints of this position statement are available from the Canadian Paediatric Society100-2204 Walkley Road Ottawa ON K1G 4G8 phone (613) 526-9397 fax (613) 526-3332
Contents bull Background bull Phototherapy bull Clinical management of hyperbilirubinemia in infants bull Exchange transfusion bull Conclusions bull References
Conflicting reports have led to confusion about the optimal management of jaundice in otherwise healthy terminfants (1-9) The lsquokinder gentler approachrsquo to neonatal hyperbilirubinemia proposed in 1992 by Newman andMaisels (8) resulted in a 1994 statement by the American Academy of Pediatrics (2) that addressed themanagement of healthy term infant without risk factors Recently there has been an increase in the number ofterm infants reported with kernicterus (10) It is important to note that while some of the infants reported withkernicterus had features that would place them in a high risk category some presented with severe jaundiceonly and no identifiable risk factors (10) The infants reported were commonly breastfed and frequentlydischarged from hospital very soon after birth (10) Nonetheless the current standards (2) for the managementof hyperbilirubinemia in the healthy term infant have become controversial This document updates information previously published by the Canadian Paediatric Society (1) It provides anoverview of the proposed management of hyperbilirubinemia based on available evidence even thoughrandomized controlled trials are not available to allow a conclusive assessment of the risk associated withhyperbilirubinemia in the clinical situations encountered in practice The objective of this overview is toestablish a management plan that will minimize the risk of kernicterus in term infants both with and withoutrisk factors Although scientific evidence has not established a clear link between specific bilirubinconcentrations and the development of kernicterus in healthy term babies information to date has beenincorporated into the following guidelines Background
Kernicterus is a neurological condition characterized by deep yellow staining of the basal nuclei Theaccompanying clinical syndrome results from the destructive changes of these neuronal populations Initiallythe signs are lethargy hypotonia and seizures later the infants may develop athetoid cerebral palsy mentalretardation and deafness When neurological signs evident in the infant permanent damage has alreadyoccurred leading to death or long term disability Therefore management strategies are aimed at preventingkernicterus
Jaundice in the Healthy Term Newborn
April 2002 Page 12 of 20
Until recently these strategies suggested maintaining serum unconjugated bilirubin concentrations below 340micromolL (20 mgdL) in healthy term infants through the use of phototherapy or exchange transfusion (11) Whileexchange transfusions had been a frequent occurrence from the 1950s to the 1970s and may sometimes still berequired phototherapy has become the mainstay of medical management of hyperbilirubinemia since that time
The cases of kernicterus originally described occurred mainly in infants with hemolytic disease Higher serumunconjugated bilirubin concentrations may be safe in healthy term infants without hemolytic disease It is notpossible to predict at what level an individual infant may develop kernicterus
Several authors have expressed serious concerns over the approach of allowing higher serum unconjugatedbilirubin concentrations to occur before investigating and treating these term infants (11-16) Brown andJohnson (10) have reported 23 cases of kernicterus occurring since 1989 16 in term and seven in near terminfants In these infants peak unconjugated bilirubin concentrations of 375 to 860 micromolL (22 to 50 mgdL)were seen All but one infant was breastfed Other associations found in these infants with kernicterus weredehydration (seven infants) glucose-6-phosphate dehydrogenase (G6PD) deficiency (five infants) ABOalloimmunization (one infant) hemolysis of unknown cause (five infants) familial etiology (one infant) andotherwise unexplained early jaundice clinically evident before 24 h of age (six infants) Similar cases have beenreported by others (1718) Although many of these babies were subsequently found to have additional riskfactors these factors were not often identified at the time the baby was noted to be jaundiced
Since the introduction in the 1990s of the kinder gentler approach to the management of hyperbilirubinemia agreat deal of confusion has arisen about approaches to the management of hyperbilirubinemia in healthy terminfants This confusion has extended to the care of borderline preterm infants who have often been treated asterm infants A recently published international survey reported considerable variability in the approach tohyperbilirubinemia and the use of phototherapy among neonatal units worldwide (3)
PhototherapyThe goal of hyperbilirubinemia treatment is to avoid bilirubin concentrations that may result in kernicterusPhototherapy remains an effective therapeutic intervention that decreases bilirubin concentrations therebypreventing elevated bilirubin levels associated with permanent sequelae
The effectiveness of phototherapy is related to the area of skin exposed and the radiant energy and thewavelength of the light (19-23) Phototherapy acts on unconjugated bilirubin to a depth of 2 mm from theepidermis Phototherapy changes the bilirubin through structural photoisomerization into water-solublelumirubin that is excreted in the urine (19) The fall in bilirubin level is proportionately greater in the skin thanin the serum (20) Therefore the infant receiving phototherapy should have as much skin as possible exposed tothe lights More intense phototherapy may be achieved by using multiple sources of phototherapy double ortriple phototherapy is recommended to optimize the skin surface exposed and therefore the efficacy ofphototherapy More detailed discussion of the physics of phototherapy has been published (124) It is important to recognize the relationship between dehydration and hyperbilirubinemia Dehydration may beassociated with increased serum bilirubin concentrations and may be exacerbated by phototherapy Alljaundiced infants should be adequately hydrated before and during phototherapy Breastfeeding is notcontraindicated in the presence of hyperbilirubinemia and should be continued More frequent breastfeedingsmay be beneficial (25)
The concentrations of bilirubin at which phototherapy might be initiated in healthy term infants and those withrisk factors are shown in Figure 1 Guidelines for phototherapy in low birth weight infants remain as previouslypublished (1) The bilirubin concentrations at which phototherapy is suggested by the Canadian PaediatricSociety in the present statement are more conservative than the current recommendations of the AmericanAcademy of Pediatrics (2) If the infant is a healthy term newborn phototherapy should be started as indicated
Jaundice in the Healthy Term Newborn
April 2002 Page 13 of 20
in the upper curve of Figure 1 If the infant has one or more risk factors a clinical decision should be made toinitiate phototherapy at the concentration indicated by the lower curve
Figure 1 Guidelines for initiation of phototherapy for hyperbilirubinemia in term infants with and without riskfactors Some risk factors include gestional age younger than 37 weeks birth weight less than 2500 ghemolysis jaundice at younger than 24 h of age sepsis and the need for resuscitation at birth
The timely recognition of risk factors is essential to minimize the danger of kernicterus The risk factors are asfollows
bull gestational age younger than 37 weeks and birth weight less than 2500 g bull hemolysis due to maternal isoimmunization G6PD deficiency spherocytosis or other causes bull jaundice at less than 24 h of age bull sepsis and bull the need for resuscitation at birth
Jaundice in the Healthy Term Newborn
April 2002 Page 14 of 20
Clinical management of hyperbilirubinemia in infants
A bilirubin level that justifies consideration of phototherapy should mandate the investigation of the cause ofhyperbilirubinemia Investigation should include a clinically pertinent history of the mother family historydescription of labour and delivery and infantrsquos clinical course (26) A physical examination should besupplemented by laboratory investigations (Table 1) including determination of unconjugated and conjugatedserum bilirubin concentrations and blood group with direct antibody test (Coombsrsquo test) and hemoglobin andhematocrit levels A complete blood count including differential white cell count and a blood smear for red cellmorphology may be indicated Further tests (eg reticulocyte count G6PD screen) may be indicated based oninitial results ethnicity or clinical presentation Testing for serum electrolytes and albumin or protein areindicated in some situations such as suspected dehydration or when bilirubin levels approach exchange valuesIn the absence of drugs or clinical states that alter the binding of bilirubin by albumin the bilirubin to albuminor the bilirubin to protein ratio reflects the free bilirubin concentration and the binding capacity of the serum(27-29) At a bilirubin concentration close to exchange transfusion levels some clinicians may wish to ensurethat serum bilirubin binding is normal (albumin 25 gL or greater protein 54 gL or greater) Values belowthese levels may be associated with low bilirubin binding and may be used by the clinician when decidingwhether further intervention (eg exchange transfusion) should take place (27)
TABLE 1 Laboratory investigation for hyperbilirubinemia in term newborn infants
Indicated (if bilirubin concentrations reach phototherapy levels) Serum total or unconjugated bilirubin concentration Serum conjugated bilirubin concentration Blood group with direct antibody test (Coombsrsquo test) Hemoglobin and hematocrit determinations
Optional (in specific clinical circumstances) Complete blood count including manual differential white cell count Blood smear for red cell morphology Reticulocyte count Glucose-6-phosphate dehydrogenase screen Serum electrolytes and albumin or protein concentrations
For infants with prolonged jaundice (lasting longer than seven days) or with conjugated hyperbilirubinemia(greater than 30 micromolL) additional investigation and management may be required and a consultation with aspecialist may be needed (30)
During the past decade most nurseries have shortened the time of hospital stay for term healthy newborninfants Early discharge of neonates means that jaundice is not often recognized at discharge (31) The CanadianPaediatric Society reiterates the importance of allowing early discharge only if a healthy status is confirmed foreach baby and appropriate follow-up is provided (32) Appropriate parental education about feeding signs ofdehydration and jaundice must be implemented in hospital nurseries Testing for serum bilirubin concentrationsmust be readily available for newborns on an out-patient basis Readmission to hospital (usually the hospital ofbirth) may be necessary for the investigation and management of hyperbilirubinemia
Exchange transfusion If phototherapy fails to control the rising bilirubin levels exchange transfusion is indicated to lower serumbilirubin concentrations For healthy term infants without risk factors exchange transfusion should beconsidered at serum unconjugated bilirubin concentrations of 400 to 430 micromolL For term infants with riskfactors the level should be 340 micromolL For infants who initially present with serum bilirubin concentrations in
Jaundice in the Healthy Term Newborn
April 2002 Page 15 of 20
excess of exchange levels intensive phototherapy should produce a decline of serum unconjugated bilirubinfrom 20 to 35 micromolL within 4 to 6 h and levels should continue to fall thereafter and remain below thethreshold for exchange transfusion If the bilirubin concentration does not decrease after adequate rehydrationand 4 to 6 h of intensive phototherapy exchange transfusion should be considered Preparation for thisincluding ensuring availability of blood should occur shortly after the admission of babies whose bilirubinconcentrations exceed exchange levels Appropriate consultation should be obtained if the etiology ofhyperbilirubinemia is unclear the infant is ill and particularly if bilirubin concentrations are approachingexchange levels Because the risks of exchange transfusion are significant the best management may bereviewed with an expert opinion from a neonatologist
Conclusions Hyperbilirubinemia in apparently healthy term newborn infants continues to hold the potential threat ofcomplications from bilirubin encephalopathy and kernicterus Careful assessment of risk factors judicious useof phototherapy appropriate laboratory monitoring and specific treatment of other disorders (eg sepsis) areessential for the optimal management of hyperbilirubinemia Appropriate laboratory facilities must be availableto measure bilirubin concentrations for out-patients in required clinical situations Readmission to hospital maybe required if phototherapy is necessary Guidelines for phototherapy are presented for term babies with andwithout identifiable risk factors
References
1 Fetus and Newborn Committee Canadian Paediatric Society Use of phototherapy for neonatalhyperbilirubinemia Can Med Assoc J 19861341237-45 2 American Academy of Pediatrics Practice parameter Management of hyperbilirubinemia in the healthy termnewborn Pediatrics 199494558-65 3 Hansen TWR Therapeutical approaches to neonatal jaundice an international survey Clin Pediatr199635309-16 4 Valaes T Koliopoulos C Koltsidopoulos A The impact of phototherapy in the management of neonatalhyperbilirubinemia comparison of historical cohorts Acta Paediatrica 199685273-6 5 Gustafson PA Boyle DW Bilirubin index a new standard for intervention Med Hypotheses 199545409-16 6 Torres-Torres M Tayaba R Weintraub A Holzman IR New perspectives on neonatal hyperbilirubinemiaMount Sinai J Med 199461424-8 7 Lazar L Litwin A Merlob P Phototherapy for neonatal nonhemolytic hyperbilirubinemia analysis ofrebound and indications for discontinuing therapy Clin Pediatr 199332264-7 8 Newman TB Maisels MJ Evaluation and treatment of jaundice in the term newborn Pediatrics 199289809-18 9 McMillan DD Lockyer JM Magnan L Akierman A Parboosingh JT Effect of educational program andinterview on adoption of guidelines for the management of neonatal hyperbilirubinemia Can Med Assoc J1991144707-12 10 Brown AK Johnson L Loss of concern about jaundice and the reemergence of kernicterus in full-terminfants in the era of managed care In Fanaroff AA Klaus MH eds The Year Book of Neonatal and PerinatalMedicine Philadelphia Mosby Yearbook 199617-28 11 Valaes T Bilirubin toxicity The problem was solved a generation ago Pediatrics 199289819-21 12 Wennberg RP Bilirubin recommendations present problems New guidelines simplistic and untestedPediatrics 199289821-2 13 Merenstein GB lsquoNewrsquo bilirubin recommendations questioned Pediatrics 199289822-3 14 Poland RL In search of a lsquogold standardrsquo for bilirubin toxicity Pediatrics 199289823-4 15 Brown AK Seidman DS Stevenson DK Jaundice in healthy term neonates Do we need new action levelsor new approaches Pediatrics 199289827-9 16 Johnson L Yet another expert opinion on bilirubin toxicity Pediatrics 199289829-31
Jaundice in the Healthy Term Newborn
April 2002 Page 16 of 20
17 MacDonald MG Hidden risks Early discharge and bilirubin toxicity due to glucose-6-phosphatedehydrogenase deficiency Pediatrics 199596734-8 18 Maisels MJ Newman TB Kernicterus in otherwise healthy breast-fed newborns Pediatrics 199596730-3 19 Vogl TP Phototherapy of neonatal hyperbilirubinemia bilirubin in unexposed areas of the skin J Pediatr197485707-1020 Rubaltelli FF Carli M The effect of light on cutaneous bilirubin Biol Neonate 197118457-62 21 Sisson TR Kendall N Shaw E et al Phototherapy of jaundice in the newborn infant 2 Effect of variouslight intensities J Pediatr 19738135-8 22 Bonta BW Warshaw JB Importance of radiant flux in the treatment of hyperbilirubinemia failure ofoverhead phototherapy units in intensive care units Pediatrics 197657502-5 23 Warshaw JB Gagliardi J Patel A A comparison of fluorescent and non-fluorescent light source forphototherapy Pediatrics 198065795-8 24 Ennever JF Blue light green light white light more light treatment of neonatal jaundice Clin Perinatol199017467-8125 Auerbach KG Gartner LM Breastfeeding and human milk their association with jaundice in the neonateClin Perinatol 19871489-108 26 Maisels MJ Jaundice in the newborn Pediatr Rev 19823305-20 27 Ahlfors CE Criteria for exchange transfusion in jaundiced newborns Pediatrics 199493488-94 28 Odell GB Storey GNB Rosenberg LA Studies in kernicterus III The saturation of serum protein withbilirubin during neonatal life and its relationship to brain damage at 5 years J Pediatr 19707612-21 29 Wirth FH Goldberg KE Lubchenco LO The neurologic outcome of infants evaluated for unboundbilirubin Pediatr Res 19759385-91 30 Haber BA Lake AM Cholestatic jaundice in the newborn Clin Perinatol 199017483-506 31 Maisels MJ Newman TB Jaundice in full-term and near-term babies who leave the hospital within 36hours The pediatricianrsquos nemesis Clin Perinatol 199825295-302 32 Fetus and Newborn Committee Canadian Paediatric Society and Society of Obstetricians andGynaecologists of Canada Facilitating discharge home following a normal term birth Paediatr Child Health19961165-8
Fetus and Newborn Committee Members Drs John Watts Department of Paediatrics Childrenrsquos Hospital ndash Hamilton Health Sciences CentreHamilton Ontario (director responsible) Douglas McMillan Department of Pediatrics Foothills HospitalCalgary Alberta (chair) Arne Ohlsson Department of Paediatrics Mount Sinai Hospital Toronto Ontario(co-chair) Deborah Davis Childrenrsquos Hospital of Eastern Ontario Ottawa Ontario Daniel Faucher RoyalVictoria Hospital Montreal Quebec (principal author) John Van Aerde Stollery Childrenrsquos Health CentreEdmonton Alberta Michael Vincer IWK-Grace Health Centre Halifax Nova ScotiaConsultant Dr Michael C Klein University of British Columbia Vancouver British Columbia (College ofFamily Physicians of Canada)Liaisons Drs James Lemon Riley Childrenrsquos Hospital Indiana University Medical Center IndianapolisIndiana (American Academy of Pediatrics) Saroj Saigal Department of Paediatrics McMaster UniversityMedical Centre Childrenrsquos Hospital ndash Hamilton Health Sciences Centre Hamilton Ontario (CPS Neonatal-Perinatal Medicine Section) Cheryl Levitt Department of Family Medicine Childrenrsquos Hospital ndash HamiltonHealth Sciences Centre Hamilton Ontario (College of Family Physicians of Canada) Catherine McCourtDirector Bureau of Reproductive amp Child Health Laboratory Centre for Disease Control Ottawa Ontario(Health Canada) Mrs Debbie Fraser-Askin Winnipeg Manitoba (Neonatal Nurses) Dr Line LeducDepartment of Obstetrics-Gynecology Hocircpital Sainte-Justine Montreal Quebec (Society of Obstetricians andGynaecologists of Canada)
Disclaimer The recommendations in this position statement do not indicate an exclusive course oftreatment or procedure to be followed Variations taking into account individual circumstances may beappropriate
Jaundice in the Healthy Term Newborn
April 2002 Page 17 of 20
APPENDIX 3Hyperbilirubinemia Risk Designation for Term and Near-Term Well Newborns
Jaundice in the Healthy Term Newborn
April 2002 Page 18 of 20
APPENDIX 4
American Academy of Pediatrics 1994 Practice parameter Management ofHyperbilirubinemia in the Healthy Term Newborn Pediatrics 94(4) 558-565
(Chart and Algorithm)
Jaundice in the Healthy Term Newborn
April 2002 Page 19 of 20
AlgorithmPediatric clinician evaluatesterm newborn with jaundice
Does the infant have signs of underlyingserious illness (lethargy apnea tachypneatemperature instability behavior changeshepatosplenomegaly persistant vomiting
or persistent feeding difficulty)
1
2
Exit this algorithm to individualizedclinical evaluation including
assessment of jaundice and underlyingdisease
Yes
3
No
Is the infant lt 37 weeks gestational age
4 Exit this algorithm to individualizedclinical evaluation including
assessment of jaundice in light ofprematurity
5
Yes
Is the mothersABO and Rh
blood typing andisoimmune
antibody screenstatus known
Is the mothersblood Rhpositive
Does themothers blood
have anyimmune
antibodies
Consider holding the infantscord blood in the blood bank incase future testing is necessary
6 7 8 9No
Yes Yes No
(Go to Box 10) (Go to Box 10) (Go to Box 10) (Go to Box 13)
No No Yes
Perform blood typing (ABO and Rh) and direct Coombs testingon the infants cord (preferably) or venous blood
10
Is the infantsblood direct
Coombs testpositive
Exit this algorithm to individualized clinical evaluationincluding assessment of jaundice and isoimmune
hemolytic disease
11 12
Yes
Are any of the following risk factors present tosuggest that nonisoimmune hemolytic disease
is possible in this infant(1) Family history of hemolytic anemia
OR(2) Family history of early or severe jaundice
OR(3) Ethnicity or geographic originassociated with hemolytic anemia
OR(4) Early or severe jaundice
Perform appropriate laboratoryassessment of infant including
(but not limited to consideration of)(1) Complete blood count differentialsmear reticulocyte count(2) G6PD screen(3) Hemoglobin electrophoresis
1314
No
No
No
(Go to Box 16)
Does the evaluation suggesthemolytic disease
15
Yes
(Go to Box 17)(Go to Box 16)
No
Jaundice in the Healthy Term Newborn
April 2002 Page 20 of 20
AlgorithmIs the infant
jaundiced andlt 24 hours of
age
Exit this algorithm to individualizedclinical evaluation includingassessment of jaundice and
nonisoimmune hemolytic disease
Is jaundiceclinicallysignificant by medical
judgment
(1) Measure infantstotal serum bilirubin(2) Go to Box 27
Healthy term infant with jaundice not clinicallysignificant by medical judgment
Follow infant in routine clinical supervision
1617
18 19
20
21
(Go to Box 22)
Yes
Yes
No
No
Is jaundicepersisting
gt 2 weeks
Does this infant haveabnormal physicalexam results dark
urine or light stools
Is jaundice persistinggt 3 weeks
Perform appropriate physical andlaboratory assessment of theinfant including possibility of
cholestatic jaundice
Provide routine carerecommend routine
feeding and follow-up Table 2 Management of Hyperbilirubinemia in the Healthy Term NewbornAgehours TSB Level mgdL (umolL)
Consider Phototherapy Exchange ExchangePhototherapy Transfusion Transfusion
if Intensive and IntensivePhototherapy PhototherapyFails
lt24 25-48 gt 12 (170) gt15 (260) gt 20 (340) gt 25 (430)49-72 gt 15 (260) gt 18 (310) gt 25 (430) gt 30 (510)gt 72 gt 17 (290) gt 20 (340) gt 25 (430) gt 30 (510)
TSB indicates total serum bilirubinPhototherapy at these TSB levels is a clinical option meaning that the intervention is availableand may be used on the basis of individual clinical judgement For a more detailed descriptionof phototherapy see the AppendixIntensive phototherapy (Appendix) should produce a decline of TSB of 1 to 2 mgdL within 4 to 6hours and the TSB level should continue to fall and remain below the threshold level for exchangetransfusion If this does not occur it is considered a failure of phototherapyTerm infants who are clinically jaundiced at lt 24 hours old are not considered healthy andrequire further evaluation (see text)
22 23
24
25
26
YesYes
No
YesNo
No 27
Algorithm Management of hyperbilirubinemia inthe healthy term infant
(From Box 19)
Jaundice in the Healthy Term Newborn
April 2002 Page 3 of 20
A Early Breastfeeding Jaundice
bull Develops within 2 to 4 days of birthbull Most likely related to infrequent breastfeeding with a limited fluid intakebull May be related to increased reabsorption of bilirubin from the bowel
B Late Breast Milk Jaundice
bull Much less commonbull Develops 4 to 7 days after birth peaks day 7 to 15 bull Cause remains unknown despite numerous theories and studies
STRATEGIES TO DECREASE INCIDENCE
I LABOR AND DELIVERY
bull avoid trauma during labor and delivery8
II BREASTFEEDING
bull provide early assistance education and support for breastfeedingbull ensure parental education regarding signs of adequate hydration signs of jaundice and feeding1 bull initiate early and frequent feedings ndash at least 8 feeds in 24 hours68 Avoid separation of mother
and babybull encourage the ingestion of colostrum to increase stooling which prevents reabsorption of bilirubinbull supplementation with water does not affect bilirubin levels and is not recommended If
supplementation is necessary due to inadequate intake the mother should pump her breasts andgive expressed breastmilk andor formula rather than water
III DISCHARGEFOLLOW-UP
bull ensure adherence to evidence-based and current postpartum discharge criteria9
bull initiate early postpartum follow-up once discharged from hospital All infants discharged prior to48 hours of age should be evaluated by a health care professional within 48 hours after discharge69
bull ensure community mechanisms for follow-up and referral between health care providers (Seeexample in Appendix 1 Management of Newborn Jaundice at Home Program)
SCREENING
I TRANSCUTANEOUS
Use of an icterometer or transcutaneous jaundice meter is sometimes used as a screening device inhealthy term infants810 Accuracy may be limited by the changing pigmentation of the skin theduration of jaundice and the effect of phototherapy11
Jaundice in the Healthy Term Newborn
April 2002
II BILIRUBIN MEASUREMENT
Several studies have looked at the predictive ability of predischarge serum bilirubin testing121314 Todate routine bilirubin investigation for healthy term newborns is not indicated However if theinfantrsquos level of jaundice is a concern at discharge it may be prudent and helpful to obtain a bilirubinlevel at the time that the PKU specimen is collected Reference to the Bhutani Graph (Appendix 3page 17) may then help to determine whether further bilirubin levels should be obtained
ASSESSMENT
I COLOUR
Kramer15 described the cephalocaudal progression of jaundice in term infants He drew attention tothe observation that jaundice starts on the head and extends towards the feet as the level rises This isuseful in deciding whether or not a baby needs to have the serum bilirubin (SBR) measured Kramerdivided the infant into 5 zones The SBR range associated with progression to the zones is as follows
Zone 1 2 3 4 5SBR
(umolL)100 150 200 250 gt250
Adapted from the Department of Neonatal Medicine Protocol Book Royal Prince Alfred Hospital University of Sydney Australia 199816
The colour of the skin should be evaluated after the skin has been blanched by pressure from the thumb in a well lit room (or natural daylight if in the home)
II AGE
Jaundice before 24 hours of age is always pathological
III FEEDING BEHAVIOUR
bull as bilirubin levels rise the baby may become more lethargicbull after the first 1-2 days of life newborns should breastfeed at lebull if baby is sleepy during feeds utilize waking techniques
IV HYDRATION
Adequate intake can be determined by the babyrsquos bull Skin turgorbull Moistness of mouthbull Weightbull Energy levelsbull Feeding patternbehavior
Page 4 of 20
ast 8 times in 24 hours
Jaundice in the Healthy Term Newborn
April 2002 Page 5 of 20
bull Elimination (See guide below)
Guide for Healthy Term Newborn Output
Day Number of Stools24 hours Number of Wet diapers24 hours
1 at least one meconium at least 1 2 at least one meconium at least 2 3 at least 1 transitional at least 3 4 at least 2 + yellowseedy at least 4 5 at least 2 + yellowseedy 5 - 6
See BCRCP British Columbia Newborn Care Path Outcomes Teaching amp Interventions document for norms27
V OTHER ILLNESS
In association with other findings jaundice may be a sign of serious illness Each jaundiced infantshould be assessed to see whether the following danger signs are present
bull Family history of significant hemolytic diseasebull Onset of jaundice within 24 hoursbull Pallor bruising petechiaebull Lethargybull Poor feedingbull Feverbull Vomitingbull Dark urine and light stoolsbull Hepatosplenomegalybull High pitched cry
CLINICAL MANAGEMENT
Clinical management is aimed at avoiding bilirubin encephalopathy with itrsquos long term neurologicalcomplications Adequate hydration is an important consideration in the infant with moderate to highbilirubin levels
Fundamental to management is a good history and physical examination together with appropriateinvestigations including
bull Unconjugated and conjugated bilirubinbull Blood group determination with a direct antibody test (Coombrsquos test)bull Hemoglobin and hematocritbull Other lab investigations (eg T4 G6PD) may be required depending on the patient assessment1
Once the serum bilirubin reaches ldquoriskrdquo levels11217 the standard treatment is the use of phototherapyandor exchange transfusion Several expert bodies have developed guidelines to assist care providers
Jaundice in the Healthy Term Newborn
April 2002 Page 6 of 20
determine the appropriate time to implement each therapy as well as how to provide the therapy mosteffectively11217
The most common guidelines utilized in risk identification and management of hyperbilirubinemia arelisted below
Appendix 2 Approach to the management of hyperbilirubinemia in term newborn infants1 A Joint Statement Canadian Paediatric Society amp College of Family
Physicians of Canada (February 2001) Appendix 3 Hyperbilirubinembia risk designation for term and near-term well newborns12 Bhutani at al (1999) Pediatrics Vol 103 No 1 p6-12
Appendix 4 Management of hyperbilirubinemia in healthy term newborns17 American Academy of Pediatrics (1994)
OTHER ISSUES IN THE MANAGEMENT OF JAUNDICE
I BREASTFEEDING AND PHOTOTHERAPY
bull Interruption of breastfeeding is usually not indicated6bull An adequate intake of milk minimizes the bilirubin level by stimulating bowel emptying
Encourage frequent and effective breastfeeding (as least 8X in 24 hours)618
bull Breastfeeding may be interrupted for diagnostic or therapeutic purposes when the bilirubin is highand there is the risk of an exchange transfusion Should this occurbull continue phototherapybull consider discontinuing breastfeeding for 24 hours or bull alternate breastfeeding with formula feeding if fluid intake is of concernbull offer positive support for breastfeeding Encourage maintenance of lactation by using a breast
pump or manual expression during the period of interrupted breastfeeding6bull Glucose water will not reduce serum bilirubin levels and may interfere with breastfeeding6 II DAYLIGHT TREATMENT
Exposing infants to indirect sunlight via a window to decrease bilirubin levels has been a longstanding practice19 Controlled studies on this treatment have not been done Mild jaundice requiresno sunlight exposure as it sends a false note to parents that their baby has a significant problem whenin fact (s)he has not If an infant has jaundice that needs treatment according to accepted guidelinesthen it should be investigated further
III FIBROPTIC PHOTOTHERAPY
Use of fibroptic or ldquobili blanketsrdquo is gaining increased interest A Cochrane Database Review20 foundthat fibroptic phototherapy was more effective at lowering serum bilirubin than no treatment but less
Jaundice in the Healthy Term Newborn
April 2002 Page 7 of 20
effective than conventional phototherapy A combination of fibroptic and conventional phototherapywas more effective than conventional phototherapy alone No conclusion could be made on thesuperiority of one fibroptic device over another No trials have been identified which support the viewthat fibroptic devices interfere less with infant care or impact less on parent-child bonding
At this time ldquobili blanketsrdquo should not be used alone to treat non-physiologic causes of jaundice orthose infants at risk of requiring an exchange transfusion
IV HOME PHOTOTHERAPY
There are few articles in the literature which address this issue21-24 With the advent of fibropticblankets and portable bilibeds home phototherapy has been implemented in a few communitiesthroughout Canada25-27 To date there are no published evidence-based guidelines on the use of homephototherapy
CLINICAL INDICATORS FOR EVALUATION
bull Serum bilirubin levels at which phototherapy is initiated (age specific in hours of life) bull Bilirubin levels at which the infant is readmitted bull Numbers of readmissions for jaundice
REFERENCES
1 Canadian Paediatric Society amp the College of Family Physicians of Canada (1999) Approach tothe management of hyperbilirubinemia in term newborn infants Paediatrics and Child Health 4(2)161-164 Access from wwwcpscaenglishstatementsFNfn98-02htm
2 Maisels J amp Newman T (1998) Jaundice in full-term and near-term babies who leave thehospital within 36 hours Clinics in Perinatology 25(2) 295-302
3 Maisels J amp Kring E (1998) Length of stay jaundice and hospital readmission Pediatrics101(6) 995-998
4 Gurpp-Phelan J Taylor J Liu L amp Davis R (1999) Early newborn hospital discharge andreadmission for mild and severe jaundice Archive of Pediatric and Adolescent Medicine 153 1283-1288)
5 Liu S Wen S McMillan D Trouton K Fowler D amp McCourt C (2000) Increasedneonatal readmission rate associated with decreased length of hospital stay at birth in CanadaCanadian Journal of Public Health 91(1) 46-50
6 American Academy of Pediatrics amp American College of Obstetricians and Gynecologists(1997) Guidelines for Perinatal Care (4rd Edition) American College of Obstetricians andGynecologists Elk Grove Village IL American Academy of Pediatrics Washington DC
7 Banks J Montgomer D Coody D amp Yetman R (1996) Hyperbilirubinemia in the termnewborn Journal of Pediatric Health Care 10(5) 228-230
Jaundice in the Healthy Term Newborn
April 2002 Page 8 of 20
8 Blackburn S (1995) Hyperbilirubinemia and neonatal jaundice Neonatal Network 14 (7)15-24
9 Canadian Paediatric Society amp the Society of Obstetricians and Gynaecologists of Canada (1996)Joint Policy Statement Facilitating discharge home following a normal term birth Paediatric amp ChildHealth1(2) 165-168Access from httpwwwcpscaenglishstatementsFNfn96-02htm
10 Bhutani V Gourley G Adler S Kreamer B Dalin C Johnson L (2000) NoninvasiveMeasurement of Total Bilirubin in a Multiracial Predischarge Newborn Population to Assess the Riskof Severe Hyperbilirubinemia Pediatrics (106) NO 2 Part 1 of 3
11 Schwoebel A amp Sakraida (1997) Hyperbilirubinemia New approaches to an old problemJournal of Perinatal and Neonatal Nursing 11(3) 78-97
12 Bhutani V Johnson L amp Sivieri E (1999) Predictive ability of a predischarge hour-specificserum bilirubin for subsequent significant hyperbilirubinemia in healthy term and near-term newbornsPediatrics 103(1) 6-14
13 Seidman D Ergaz Z Paz I Laor A Revel-Vilk S Stevenson D amp Gale R (1999)Predicting the risk of jaundice in fullterm healthy newborns A prospective population-based studyJournal of Perinatology 19(8) 564-567
14 Alpay F Sarici U Tosuncuk D Serdar M Inanc N amp Gokcay E (2000) The value offirst-day bilirubin measurement in predicting the development of significant hyperbilirubinemia inhealth term newborns Pediatrics 106(2)
15 Kramer L 1969 Advancement of dermal icterus in the jaundiced newborn American Journal ofDiseases in Children 118 454-458
16 Royal Prince Alfred Hospital 1998 The department of neonatal medicine protocol bookjaundice Sydney Author Accessed May 2001 fromwwwcsnswgovaurpaneonatalhtmlnewprotjaund2htm
17 American Academy of Pediatrics (1994) Practice parameter Management ofhyperbilirubinemia in the healthy term newborn Pediatrics 94(4) 558-565) httpwwwaaporgpolicyhyperbhtm
18 International Lactation Consultant Association (1999) Evidence-Based Guidelines forBreastfeeding Management During the First Fourteen Days Raleigh NC Author
19 Mohrbacher N amp Stock J (1997) The Breastfeeding Answer Book Illinois La Leche League
20 Mills J amp Tudehope D (2001) The Cochrane Database of Systemic Reviews Fibreopticphototherapy for neonatal jaundice Volume (Issue 1)
21 Ludwig M (1990) Phototherapy in the home setting Journal of Pediatric Health Care 4(6)304-308
Jaundice in the Healthy Term Newborn
April 2002 Page 9 of 20
22 Hamelin K amp Seshia M (1998) Home phototherapy for uncomplicated neonatal jaundiceCanadian Nurse Jan 39-40
23 Murphy B amp Welch R (1992) Home phototherapy for the jaundiced full-term newbornJournal of Home Health Care Practitioner 5(1) 26-33
24 British Columbia Reproductive Care Program (2001) British Columbia Newborn Care PathOutcomes Teaching amp Interventions Vancouver Author
25 Campbell River Hospital (2000) Protocol Hyperbilirubinemia ndash Home PhototherapyManagement Campbell River BC Author
26 Mississauga Hospital (1994) Protocol Home Phototherapy Programme Mississauga ONAuthor
27 University of Manitoba Health Science Centre () Protocol Home Phototherapy ProgramWinnepeg Author Access from httpwwwumanitobacawomens_healthhschomethtm
WEB RESOURCES
httpwwwaaporgpolicyhyperbhtm
wwwcpscaenglishstatementsFNfn98-02htm
httpwwwcpscaenglishstatementsFNfn96-02htm
wwwcsnswgovaurpaneonatalhtmlnewprotjaund2htm
httpwwwumanitobacawomens_healthhschomethtm
Jaundice in the Healthy Term Newborn
April 2002 Page 10 of 20
Management of Newborn Jaundice at Home Program
Referral for the Healthy Term Infant
PHN Identifies jaundice in the newborn
1 Preterm Infant RhABO incompatibility2 Look or act ill (eg lethargic apnea tachycardia
temperature unstable poor feeding changed behaviorpersistant vomiting insufficient voidingstooling)
No
Family hx of early or severejaundice Ethnicity relevant(Mediterranean SE Asian)
No
Infant less than24 hrs
No
Is jaundiceclinically
significant
No
Jaundice persistedgt 2 weeks
Jaundice gt3weeks
Routinecare and
feedsNo
Routinecare and
feedsNo
RoutineClinical
Supervis-ion
No
Refer to MD ASAPYes
Refer to MD forinvestigationeg
G6PD SpherocytosisYes
Refer to MD fornon - isoimmune
hemolyticdisease
investigation
Yes
Refer to MD forfollow-up with total
serum bilirubinYes
Any abnormal physicalfindings Dark urine
light stoolsRefer to MDYes Yes
Refer to MDYes
APPENDIX 1 (Example)
Developed by the Coordinated Maternity Standards Committee South FraserHealth Region and Dr K Danso Pediatrician Surrey Memorial Hospital
Revised 1997 Copied with permission
Jaundice in the Healthy Term Newborn
April 2002 Page 11 of 20
APPENDIX 2
Approach to the Management of Hyperbilirubinemiain Term Newborn Infants
A Joint Statement with the College of Family Physicians of CanadaPaediatrics amp Child Health 19994(2)161-164Reference No FN98-02Reaffirmed February 2001
Reprints of this position statement are available from the Canadian Paediatric Society100-2204 Walkley Road Ottawa ON K1G 4G8 phone (613) 526-9397 fax (613) 526-3332
Contents bull Background bull Phototherapy bull Clinical management of hyperbilirubinemia in infants bull Exchange transfusion bull Conclusions bull References
Conflicting reports have led to confusion about the optimal management of jaundice in otherwise healthy terminfants (1-9) The lsquokinder gentler approachrsquo to neonatal hyperbilirubinemia proposed in 1992 by Newman andMaisels (8) resulted in a 1994 statement by the American Academy of Pediatrics (2) that addressed themanagement of healthy term infant without risk factors Recently there has been an increase in the number ofterm infants reported with kernicterus (10) It is important to note that while some of the infants reported withkernicterus had features that would place them in a high risk category some presented with severe jaundiceonly and no identifiable risk factors (10) The infants reported were commonly breastfed and frequentlydischarged from hospital very soon after birth (10) Nonetheless the current standards (2) for the managementof hyperbilirubinemia in the healthy term infant have become controversial This document updates information previously published by the Canadian Paediatric Society (1) It provides anoverview of the proposed management of hyperbilirubinemia based on available evidence even thoughrandomized controlled trials are not available to allow a conclusive assessment of the risk associated withhyperbilirubinemia in the clinical situations encountered in practice The objective of this overview is toestablish a management plan that will minimize the risk of kernicterus in term infants both with and withoutrisk factors Although scientific evidence has not established a clear link between specific bilirubinconcentrations and the development of kernicterus in healthy term babies information to date has beenincorporated into the following guidelines Background
Kernicterus is a neurological condition characterized by deep yellow staining of the basal nuclei Theaccompanying clinical syndrome results from the destructive changes of these neuronal populations Initiallythe signs are lethargy hypotonia and seizures later the infants may develop athetoid cerebral palsy mentalretardation and deafness When neurological signs evident in the infant permanent damage has alreadyoccurred leading to death or long term disability Therefore management strategies are aimed at preventingkernicterus
Jaundice in the Healthy Term Newborn
April 2002 Page 12 of 20
Until recently these strategies suggested maintaining serum unconjugated bilirubin concentrations below 340micromolL (20 mgdL) in healthy term infants through the use of phototherapy or exchange transfusion (11) Whileexchange transfusions had been a frequent occurrence from the 1950s to the 1970s and may sometimes still berequired phototherapy has become the mainstay of medical management of hyperbilirubinemia since that time
The cases of kernicterus originally described occurred mainly in infants with hemolytic disease Higher serumunconjugated bilirubin concentrations may be safe in healthy term infants without hemolytic disease It is notpossible to predict at what level an individual infant may develop kernicterus
Several authors have expressed serious concerns over the approach of allowing higher serum unconjugatedbilirubin concentrations to occur before investigating and treating these term infants (11-16) Brown andJohnson (10) have reported 23 cases of kernicterus occurring since 1989 16 in term and seven in near terminfants In these infants peak unconjugated bilirubin concentrations of 375 to 860 micromolL (22 to 50 mgdL)were seen All but one infant was breastfed Other associations found in these infants with kernicterus weredehydration (seven infants) glucose-6-phosphate dehydrogenase (G6PD) deficiency (five infants) ABOalloimmunization (one infant) hemolysis of unknown cause (five infants) familial etiology (one infant) andotherwise unexplained early jaundice clinically evident before 24 h of age (six infants) Similar cases have beenreported by others (1718) Although many of these babies were subsequently found to have additional riskfactors these factors were not often identified at the time the baby was noted to be jaundiced
Since the introduction in the 1990s of the kinder gentler approach to the management of hyperbilirubinemia agreat deal of confusion has arisen about approaches to the management of hyperbilirubinemia in healthy terminfants This confusion has extended to the care of borderline preterm infants who have often been treated asterm infants A recently published international survey reported considerable variability in the approach tohyperbilirubinemia and the use of phototherapy among neonatal units worldwide (3)
PhototherapyThe goal of hyperbilirubinemia treatment is to avoid bilirubin concentrations that may result in kernicterusPhototherapy remains an effective therapeutic intervention that decreases bilirubin concentrations therebypreventing elevated bilirubin levels associated with permanent sequelae
The effectiveness of phototherapy is related to the area of skin exposed and the radiant energy and thewavelength of the light (19-23) Phototherapy acts on unconjugated bilirubin to a depth of 2 mm from theepidermis Phototherapy changes the bilirubin through structural photoisomerization into water-solublelumirubin that is excreted in the urine (19) The fall in bilirubin level is proportionately greater in the skin thanin the serum (20) Therefore the infant receiving phototherapy should have as much skin as possible exposed tothe lights More intense phototherapy may be achieved by using multiple sources of phototherapy double ortriple phototherapy is recommended to optimize the skin surface exposed and therefore the efficacy ofphototherapy More detailed discussion of the physics of phototherapy has been published (124) It is important to recognize the relationship between dehydration and hyperbilirubinemia Dehydration may beassociated with increased serum bilirubin concentrations and may be exacerbated by phototherapy Alljaundiced infants should be adequately hydrated before and during phototherapy Breastfeeding is notcontraindicated in the presence of hyperbilirubinemia and should be continued More frequent breastfeedingsmay be beneficial (25)
The concentrations of bilirubin at which phototherapy might be initiated in healthy term infants and those withrisk factors are shown in Figure 1 Guidelines for phototherapy in low birth weight infants remain as previouslypublished (1) The bilirubin concentrations at which phototherapy is suggested by the Canadian PaediatricSociety in the present statement are more conservative than the current recommendations of the AmericanAcademy of Pediatrics (2) If the infant is a healthy term newborn phototherapy should be started as indicated
Jaundice in the Healthy Term Newborn
April 2002 Page 13 of 20
in the upper curve of Figure 1 If the infant has one or more risk factors a clinical decision should be made toinitiate phototherapy at the concentration indicated by the lower curve
Figure 1 Guidelines for initiation of phototherapy for hyperbilirubinemia in term infants with and without riskfactors Some risk factors include gestional age younger than 37 weeks birth weight less than 2500 ghemolysis jaundice at younger than 24 h of age sepsis and the need for resuscitation at birth
The timely recognition of risk factors is essential to minimize the danger of kernicterus The risk factors are asfollows
bull gestational age younger than 37 weeks and birth weight less than 2500 g bull hemolysis due to maternal isoimmunization G6PD deficiency spherocytosis or other causes bull jaundice at less than 24 h of age bull sepsis and bull the need for resuscitation at birth
Jaundice in the Healthy Term Newborn
April 2002 Page 14 of 20
Clinical management of hyperbilirubinemia in infants
A bilirubin level that justifies consideration of phototherapy should mandate the investigation of the cause ofhyperbilirubinemia Investigation should include a clinically pertinent history of the mother family historydescription of labour and delivery and infantrsquos clinical course (26) A physical examination should besupplemented by laboratory investigations (Table 1) including determination of unconjugated and conjugatedserum bilirubin concentrations and blood group with direct antibody test (Coombsrsquo test) and hemoglobin andhematocrit levels A complete blood count including differential white cell count and a blood smear for red cellmorphology may be indicated Further tests (eg reticulocyte count G6PD screen) may be indicated based oninitial results ethnicity or clinical presentation Testing for serum electrolytes and albumin or protein areindicated in some situations such as suspected dehydration or when bilirubin levels approach exchange valuesIn the absence of drugs or clinical states that alter the binding of bilirubin by albumin the bilirubin to albuminor the bilirubin to protein ratio reflects the free bilirubin concentration and the binding capacity of the serum(27-29) At a bilirubin concentration close to exchange transfusion levels some clinicians may wish to ensurethat serum bilirubin binding is normal (albumin 25 gL or greater protein 54 gL or greater) Values belowthese levels may be associated with low bilirubin binding and may be used by the clinician when decidingwhether further intervention (eg exchange transfusion) should take place (27)
TABLE 1 Laboratory investigation for hyperbilirubinemia in term newborn infants
Indicated (if bilirubin concentrations reach phototherapy levels) Serum total or unconjugated bilirubin concentration Serum conjugated bilirubin concentration Blood group with direct antibody test (Coombsrsquo test) Hemoglobin and hematocrit determinations
Optional (in specific clinical circumstances) Complete blood count including manual differential white cell count Blood smear for red cell morphology Reticulocyte count Glucose-6-phosphate dehydrogenase screen Serum electrolytes and albumin or protein concentrations
For infants with prolonged jaundice (lasting longer than seven days) or with conjugated hyperbilirubinemia(greater than 30 micromolL) additional investigation and management may be required and a consultation with aspecialist may be needed (30)
During the past decade most nurseries have shortened the time of hospital stay for term healthy newborninfants Early discharge of neonates means that jaundice is not often recognized at discharge (31) The CanadianPaediatric Society reiterates the importance of allowing early discharge only if a healthy status is confirmed foreach baby and appropriate follow-up is provided (32) Appropriate parental education about feeding signs ofdehydration and jaundice must be implemented in hospital nurseries Testing for serum bilirubin concentrationsmust be readily available for newborns on an out-patient basis Readmission to hospital (usually the hospital ofbirth) may be necessary for the investigation and management of hyperbilirubinemia
Exchange transfusion If phototherapy fails to control the rising bilirubin levels exchange transfusion is indicated to lower serumbilirubin concentrations For healthy term infants without risk factors exchange transfusion should beconsidered at serum unconjugated bilirubin concentrations of 400 to 430 micromolL For term infants with riskfactors the level should be 340 micromolL For infants who initially present with serum bilirubin concentrations in
Jaundice in the Healthy Term Newborn
April 2002 Page 15 of 20
excess of exchange levels intensive phototherapy should produce a decline of serum unconjugated bilirubinfrom 20 to 35 micromolL within 4 to 6 h and levels should continue to fall thereafter and remain below thethreshold for exchange transfusion If the bilirubin concentration does not decrease after adequate rehydrationand 4 to 6 h of intensive phototherapy exchange transfusion should be considered Preparation for thisincluding ensuring availability of blood should occur shortly after the admission of babies whose bilirubinconcentrations exceed exchange levels Appropriate consultation should be obtained if the etiology ofhyperbilirubinemia is unclear the infant is ill and particularly if bilirubin concentrations are approachingexchange levels Because the risks of exchange transfusion are significant the best management may bereviewed with an expert opinion from a neonatologist
Conclusions Hyperbilirubinemia in apparently healthy term newborn infants continues to hold the potential threat ofcomplications from bilirubin encephalopathy and kernicterus Careful assessment of risk factors judicious useof phototherapy appropriate laboratory monitoring and specific treatment of other disorders (eg sepsis) areessential for the optimal management of hyperbilirubinemia Appropriate laboratory facilities must be availableto measure bilirubin concentrations for out-patients in required clinical situations Readmission to hospital maybe required if phototherapy is necessary Guidelines for phototherapy are presented for term babies with andwithout identifiable risk factors
References
1 Fetus and Newborn Committee Canadian Paediatric Society Use of phototherapy for neonatalhyperbilirubinemia Can Med Assoc J 19861341237-45 2 American Academy of Pediatrics Practice parameter Management of hyperbilirubinemia in the healthy termnewborn Pediatrics 199494558-65 3 Hansen TWR Therapeutical approaches to neonatal jaundice an international survey Clin Pediatr199635309-16 4 Valaes T Koliopoulos C Koltsidopoulos A The impact of phototherapy in the management of neonatalhyperbilirubinemia comparison of historical cohorts Acta Paediatrica 199685273-6 5 Gustafson PA Boyle DW Bilirubin index a new standard for intervention Med Hypotheses 199545409-16 6 Torres-Torres M Tayaba R Weintraub A Holzman IR New perspectives on neonatal hyperbilirubinemiaMount Sinai J Med 199461424-8 7 Lazar L Litwin A Merlob P Phototherapy for neonatal nonhemolytic hyperbilirubinemia analysis ofrebound and indications for discontinuing therapy Clin Pediatr 199332264-7 8 Newman TB Maisels MJ Evaluation and treatment of jaundice in the term newborn Pediatrics 199289809-18 9 McMillan DD Lockyer JM Magnan L Akierman A Parboosingh JT Effect of educational program andinterview on adoption of guidelines for the management of neonatal hyperbilirubinemia Can Med Assoc J1991144707-12 10 Brown AK Johnson L Loss of concern about jaundice and the reemergence of kernicterus in full-terminfants in the era of managed care In Fanaroff AA Klaus MH eds The Year Book of Neonatal and PerinatalMedicine Philadelphia Mosby Yearbook 199617-28 11 Valaes T Bilirubin toxicity The problem was solved a generation ago Pediatrics 199289819-21 12 Wennberg RP Bilirubin recommendations present problems New guidelines simplistic and untestedPediatrics 199289821-2 13 Merenstein GB lsquoNewrsquo bilirubin recommendations questioned Pediatrics 199289822-3 14 Poland RL In search of a lsquogold standardrsquo for bilirubin toxicity Pediatrics 199289823-4 15 Brown AK Seidman DS Stevenson DK Jaundice in healthy term neonates Do we need new action levelsor new approaches Pediatrics 199289827-9 16 Johnson L Yet another expert opinion on bilirubin toxicity Pediatrics 199289829-31
Jaundice in the Healthy Term Newborn
April 2002 Page 16 of 20
17 MacDonald MG Hidden risks Early discharge and bilirubin toxicity due to glucose-6-phosphatedehydrogenase deficiency Pediatrics 199596734-8 18 Maisels MJ Newman TB Kernicterus in otherwise healthy breast-fed newborns Pediatrics 199596730-3 19 Vogl TP Phototherapy of neonatal hyperbilirubinemia bilirubin in unexposed areas of the skin J Pediatr197485707-1020 Rubaltelli FF Carli M The effect of light on cutaneous bilirubin Biol Neonate 197118457-62 21 Sisson TR Kendall N Shaw E et al Phototherapy of jaundice in the newborn infant 2 Effect of variouslight intensities J Pediatr 19738135-8 22 Bonta BW Warshaw JB Importance of radiant flux in the treatment of hyperbilirubinemia failure ofoverhead phototherapy units in intensive care units Pediatrics 197657502-5 23 Warshaw JB Gagliardi J Patel A A comparison of fluorescent and non-fluorescent light source forphototherapy Pediatrics 198065795-8 24 Ennever JF Blue light green light white light more light treatment of neonatal jaundice Clin Perinatol199017467-8125 Auerbach KG Gartner LM Breastfeeding and human milk their association with jaundice in the neonateClin Perinatol 19871489-108 26 Maisels MJ Jaundice in the newborn Pediatr Rev 19823305-20 27 Ahlfors CE Criteria for exchange transfusion in jaundiced newborns Pediatrics 199493488-94 28 Odell GB Storey GNB Rosenberg LA Studies in kernicterus III The saturation of serum protein withbilirubin during neonatal life and its relationship to brain damage at 5 years J Pediatr 19707612-21 29 Wirth FH Goldberg KE Lubchenco LO The neurologic outcome of infants evaluated for unboundbilirubin Pediatr Res 19759385-91 30 Haber BA Lake AM Cholestatic jaundice in the newborn Clin Perinatol 199017483-506 31 Maisels MJ Newman TB Jaundice in full-term and near-term babies who leave the hospital within 36hours The pediatricianrsquos nemesis Clin Perinatol 199825295-302 32 Fetus and Newborn Committee Canadian Paediatric Society and Society of Obstetricians andGynaecologists of Canada Facilitating discharge home following a normal term birth Paediatr Child Health19961165-8
Fetus and Newborn Committee Members Drs John Watts Department of Paediatrics Childrenrsquos Hospital ndash Hamilton Health Sciences CentreHamilton Ontario (director responsible) Douglas McMillan Department of Pediatrics Foothills HospitalCalgary Alberta (chair) Arne Ohlsson Department of Paediatrics Mount Sinai Hospital Toronto Ontario(co-chair) Deborah Davis Childrenrsquos Hospital of Eastern Ontario Ottawa Ontario Daniel Faucher RoyalVictoria Hospital Montreal Quebec (principal author) John Van Aerde Stollery Childrenrsquos Health CentreEdmonton Alberta Michael Vincer IWK-Grace Health Centre Halifax Nova ScotiaConsultant Dr Michael C Klein University of British Columbia Vancouver British Columbia (College ofFamily Physicians of Canada)Liaisons Drs James Lemon Riley Childrenrsquos Hospital Indiana University Medical Center IndianapolisIndiana (American Academy of Pediatrics) Saroj Saigal Department of Paediatrics McMaster UniversityMedical Centre Childrenrsquos Hospital ndash Hamilton Health Sciences Centre Hamilton Ontario (CPS Neonatal-Perinatal Medicine Section) Cheryl Levitt Department of Family Medicine Childrenrsquos Hospital ndash HamiltonHealth Sciences Centre Hamilton Ontario (College of Family Physicians of Canada) Catherine McCourtDirector Bureau of Reproductive amp Child Health Laboratory Centre for Disease Control Ottawa Ontario(Health Canada) Mrs Debbie Fraser-Askin Winnipeg Manitoba (Neonatal Nurses) Dr Line LeducDepartment of Obstetrics-Gynecology Hocircpital Sainte-Justine Montreal Quebec (Society of Obstetricians andGynaecologists of Canada)
Disclaimer The recommendations in this position statement do not indicate an exclusive course oftreatment or procedure to be followed Variations taking into account individual circumstances may beappropriate
Jaundice in the Healthy Term Newborn
April 2002 Page 17 of 20
APPENDIX 3Hyperbilirubinemia Risk Designation for Term and Near-Term Well Newborns
Jaundice in the Healthy Term Newborn
April 2002 Page 18 of 20
APPENDIX 4
American Academy of Pediatrics 1994 Practice parameter Management ofHyperbilirubinemia in the Healthy Term Newborn Pediatrics 94(4) 558-565
(Chart and Algorithm)
Jaundice in the Healthy Term Newborn
April 2002 Page 19 of 20
AlgorithmPediatric clinician evaluatesterm newborn with jaundice
Does the infant have signs of underlyingserious illness (lethargy apnea tachypneatemperature instability behavior changeshepatosplenomegaly persistant vomiting
or persistent feeding difficulty)
1
2
Exit this algorithm to individualizedclinical evaluation including
assessment of jaundice and underlyingdisease
Yes
3
No
Is the infant lt 37 weeks gestational age
4 Exit this algorithm to individualizedclinical evaluation including
assessment of jaundice in light ofprematurity
5
Yes
Is the mothersABO and Rh
blood typing andisoimmune
antibody screenstatus known
Is the mothersblood Rhpositive
Does themothers blood
have anyimmune
antibodies
Consider holding the infantscord blood in the blood bank incase future testing is necessary
6 7 8 9No
Yes Yes No
(Go to Box 10) (Go to Box 10) (Go to Box 10) (Go to Box 13)
No No Yes
Perform blood typing (ABO and Rh) and direct Coombs testingon the infants cord (preferably) or venous blood
10
Is the infantsblood direct
Coombs testpositive
Exit this algorithm to individualized clinical evaluationincluding assessment of jaundice and isoimmune
hemolytic disease
11 12
Yes
Are any of the following risk factors present tosuggest that nonisoimmune hemolytic disease
is possible in this infant(1) Family history of hemolytic anemia
OR(2) Family history of early or severe jaundice
OR(3) Ethnicity or geographic originassociated with hemolytic anemia
OR(4) Early or severe jaundice
Perform appropriate laboratoryassessment of infant including
(but not limited to consideration of)(1) Complete blood count differentialsmear reticulocyte count(2) G6PD screen(3) Hemoglobin electrophoresis
1314
No
No
No
(Go to Box 16)
Does the evaluation suggesthemolytic disease
15
Yes
(Go to Box 17)(Go to Box 16)
No
Jaundice in the Healthy Term Newborn
April 2002 Page 20 of 20
AlgorithmIs the infant
jaundiced andlt 24 hours of
age
Exit this algorithm to individualizedclinical evaluation includingassessment of jaundice and
nonisoimmune hemolytic disease
Is jaundiceclinicallysignificant by medical
judgment
(1) Measure infantstotal serum bilirubin(2) Go to Box 27
Healthy term infant with jaundice not clinicallysignificant by medical judgment
Follow infant in routine clinical supervision
1617
18 19
20
21
(Go to Box 22)
Yes
Yes
No
No
Is jaundicepersisting
gt 2 weeks
Does this infant haveabnormal physicalexam results dark
urine or light stools
Is jaundice persistinggt 3 weeks
Perform appropriate physical andlaboratory assessment of theinfant including possibility of
cholestatic jaundice
Provide routine carerecommend routine
feeding and follow-up Table 2 Management of Hyperbilirubinemia in the Healthy Term NewbornAgehours TSB Level mgdL (umolL)
Consider Phototherapy Exchange ExchangePhototherapy Transfusion Transfusion
if Intensive and IntensivePhototherapy PhototherapyFails
lt24 25-48 gt 12 (170) gt15 (260) gt 20 (340) gt 25 (430)49-72 gt 15 (260) gt 18 (310) gt 25 (430) gt 30 (510)gt 72 gt 17 (290) gt 20 (340) gt 25 (430) gt 30 (510)
TSB indicates total serum bilirubinPhototherapy at these TSB levels is a clinical option meaning that the intervention is availableand may be used on the basis of individual clinical judgement For a more detailed descriptionof phototherapy see the AppendixIntensive phototherapy (Appendix) should produce a decline of TSB of 1 to 2 mgdL within 4 to 6hours and the TSB level should continue to fall and remain below the threshold level for exchangetransfusion If this does not occur it is considered a failure of phototherapyTerm infants who are clinically jaundiced at lt 24 hours old are not considered healthy andrequire further evaluation (see text)
22 23
24
25
26
YesYes
No
YesNo
No 27
Algorithm Management of hyperbilirubinemia inthe healthy term infant
(From Box 19)
Jaundice in the Healthy Term Newborn
April 2002
II BILIRUBIN MEASUREMENT
Several studies have looked at the predictive ability of predischarge serum bilirubin testing121314 Todate routine bilirubin investigation for healthy term newborns is not indicated However if theinfantrsquos level of jaundice is a concern at discharge it may be prudent and helpful to obtain a bilirubinlevel at the time that the PKU specimen is collected Reference to the Bhutani Graph (Appendix 3page 17) may then help to determine whether further bilirubin levels should be obtained
ASSESSMENT
I COLOUR
Kramer15 described the cephalocaudal progression of jaundice in term infants He drew attention tothe observation that jaundice starts on the head and extends towards the feet as the level rises This isuseful in deciding whether or not a baby needs to have the serum bilirubin (SBR) measured Kramerdivided the infant into 5 zones The SBR range associated with progression to the zones is as follows
Zone 1 2 3 4 5SBR
(umolL)100 150 200 250 gt250
Adapted from the Department of Neonatal Medicine Protocol Book Royal Prince Alfred Hospital University of Sydney Australia 199816
The colour of the skin should be evaluated after the skin has been blanched by pressure from the thumb in a well lit room (or natural daylight if in the home)
II AGE
Jaundice before 24 hours of age is always pathological
III FEEDING BEHAVIOUR
bull as bilirubin levels rise the baby may become more lethargicbull after the first 1-2 days of life newborns should breastfeed at lebull if baby is sleepy during feeds utilize waking techniques
IV HYDRATION
Adequate intake can be determined by the babyrsquos bull Skin turgorbull Moistness of mouthbull Weightbull Energy levelsbull Feeding patternbehavior
Page 4 of 20
ast 8 times in 24 hours
Jaundice in the Healthy Term Newborn
April 2002 Page 5 of 20
bull Elimination (See guide below)
Guide for Healthy Term Newborn Output
Day Number of Stools24 hours Number of Wet diapers24 hours
1 at least one meconium at least 1 2 at least one meconium at least 2 3 at least 1 transitional at least 3 4 at least 2 + yellowseedy at least 4 5 at least 2 + yellowseedy 5 - 6
See BCRCP British Columbia Newborn Care Path Outcomes Teaching amp Interventions document for norms27
V OTHER ILLNESS
In association with other findings jaundice may be a sign of serious illness Each jaundiced infantshould be assessed to see whether the following danger signs are present
bull Family history of significant hemolytic diseasebull Onset of jaundice within 24 hoursbull Pallor bruising petechiaebull Lethargybull Poor feedingbull Feverbull Vomitingbull Dark urine and light stoolsbull Hepatosplenomegalybull High pitched cry
CLINICAL MANAGEMENT
Clinical management is aimed at avoiding bilirubin encephalopathy with itrsquos long term neurologicalcomplications Adequate hydration is an important consideration in the infant with moderate to highbilirubin levels
Fundamental to management is a good history and physical examination together with appropriateinvestigations including
bull Unconjugated and conjugated bilirubinbull Blood group determination with a direct antibody test (Coombrsquos test)bull Hemoglobin and hematocritbull Other lab investigations (eg T4 G6PD) may be required depending on the patient assessment1
Once the serum bilirubin reaches ldquoriskrdquo levels11217 the standard treatment is the use of phototherapyandor exchange transfusion Several expert bodies have developed guidelines to assist care providers
Jaundice in the Healthy Term Newborn
April 2002 Page 6 of 20
determine the appropriate time to implement each therapy as well as how to provide the therapy mosteffectively11217
The most common guidelines utilized in risk identification and management of hyperbilirubinemia arelisted below
Appendix 2 Approach to the management of hyperbilirubinemia in term newborn infants1 A Joint Statement Canadian Paediatric Society amp College of Family
Physicians of Canada (February 2001) Appendix 3 Hyperbilirubinembia risk designation for term and near-term well newborns12 Bhutani at al (1999) Pediatrics Vol 103 No 1 p6-12
Appendix 4 Management of hyperbilirubinemia in healthy term newborns17 American Academy of Pediatrics (1994)
OTHER ISSUES IN THE MANAGEMENT OF JAUNDICE
I BREASTFEEDING AND PHOTOTHERAPY
bull Interruption of breastfeeding is usually not indicated6bull An adequate intake of milk minimizes the bilirubin level by stimulating bowel emptying
Encourage frequent and effective breastfeeding (as least 8X in 24 hours)618
bull Breastfeeding may be interrupted for diagnostic or therapeutic purposes when the bilirubin is highand there is the risk of an exchange transfusion Should this occurbull continue phototherapybull consider discontinuing breastfeeding for 24 hours or bull alternate breastfeeding with formula feeding if fluid intake is of concernbull offer positive support for breastfeeding Encourage maintenance of lactation by using a breast
pump or manual expression during the period of interrupted breastfeeding6bull Glucose water will not reduce serum bilirubin levels and may interfere with breastfeeding6 II DAYLIGHT TREATMENT
Exposing infants to indirect sunlight via a window to decrease bilirubin levels has been a longstanding practice19 Controlled studies on this treatment have not been done Mild jaundice requiresno sunlight exposure as it sends a false note to parents that their baby has a significant problem whenin fact (s)he has not If an infant has jaundice that needs treatment according to accepted guidelinesthen it should be investigated further
III FIBROPTIC PHOTOTHERAPY
Use of fibroptic or ldquobili blanketsrdquo is gaining increased interest A Cochrane Database Review20 foundthat fibroptic phototherapy was more effective at lowering serum bilirubin than no treatment but less
Jaundice in the Healthy Term Newborn
April 2002 Page 7 of 20
effective than conventional phototherapy A combination of fibroptic and conventional phototherapywas more effective than conventional phototherapy alone No conclusion could be made on thesuperiority of one fibroptic device over another No trials have been identified which support the viewthat fibroptic devices interfere less with infant care or impact less on parent-child bonding
At this time ldquobili blanketsrdquo should not be used alone to treat non-physiologic causes of jaundice orthose infants at risk of requiring an exchange transfusion
IV HOME PHOTOTHERAPY
There are few articles in the literature which address this issue21-24 With the advent of fibropticblankets and portable bilibeds home phototherapy has been implemented in a few communitiesthroughout Canada25-27 To date there are no published evidence-based guidelines on the use of homephototherapy
CLINICAL INDICATORS FOR EVALUATION
bull Serum bilirubin levels at which phototherapy is initiated (age specific in hours of life) bull Bilirubin levels at which the infant is readmitted bull Numbers of readmissions for jaundice
REFERENCES
1 Canadian Paediatric Society amp the College of Family Physicians of Canada (1999) Approach tothe management of hyperbilirubinemia in term newborn infants Paediatrics and Child Health 4(2)161-164 Access from wwwcpscaenglishstatementsFNfn98-02htm
2 Maisels J amp Newman T (1998) Jaundice in full-term and near-term babies who leave thehospital within 36 hours Clinics in Perinatology 25(2) 295-302
3 Maisels J amp Kring E (1998) Length of stay jaundice and hospital readmission Pediatrics101(6) 995-998
4 Gurpp-Phelan J Taylor J Liu L amp Davis R (1999) Early newborn hospital discharge andreadmission for mild and severe jaundice Archive of Pediatric and Adolescent Medicine 153 1283-1288)
5 Liu S Wen S McMillan D Trouton K Fowler D amp McCourt C (2000) Increasedneonatal readmission rate associated with decreased length of hospital stay at birth in CanadaCanadian Journal of Public Health 91(1) 46-50
6 American Academy of Pediatrics amp American College of Obstetricians and Gynecologists(1997) Guidelines for Perinatal Care (4rd Edition) American College of Obstetricians andGynecologists Elk Grove Village IL American Academy of Pediatrics Washington DC
7 Banks J Montgomer D Coody D amp Yetman R (1996) Hyperbilirubinemia in the termnewborn Journal of Pediatric Health Care 10(5) 228-230
Jaundice in the Healthy Term Newborn
April 2002 Page 8 of 20
8 Blackburn S (1995) Hyperbilirubinemia and neonatal jaundice Neonatal Network 14 (7)15-24
9 Canadian Paediatric Society amp the Society of Obstetricians and Gynaecologists of Canada (1996)Joint Policy Statement Facilitating discharge home following a normal term birth Paediatric amp ChildHealth1(2) 165-168Access from httpwwwcpscaenglishstatementsFNfn96-02htm
10 Bhutani V Gourley G Adler S Kreamer B Dalin C Johnson L (2000) NoninvasiveMeasurement of Total Bilirubin in a Multiracial Predischarge Newborn Population to Assess the Riskof Severe Hyperbilirubinemia Pediatrics (106) NO 2 Part 1 of 3
11 Schwoebel A amp Sakraida (1997) Hyperbilirubinemia New approaches to an old problemJournal of Perinatal and Neonatal Nursing 11(3) 78-97
12 Bhutani V Johnson L amp Sivieri E (1999) Predictive ability of a predischarge hour-specificserum bilirubin for subsequent significant hyperbilirubinemia in healthy term and near-term newbornsPediatrics 103(1) 6-14
13 Seidman D Ergaz Z Paz I Laor A Revel-Vilk S Stevenson D amp Gale R (1999)Predicting the risk of jaundice in fullterm healthy newborns A prospective population-based studyJournal of Perinatology 19(8) 564-567
14 Alpay F Sarici U Tosuncuk D Serdar M Inanc N amp Gokcay E (2000) The value offirst-day bilirubin measurement in predicting the development of significant hyperbilirubinemia inhealth term newborns Pediatrics 106(2)
15 Kramer L 1969 Advancement of dermal icterus in the jaundiced newborn American Journal ofDiseases in Children 118 454-458
16 Royal Prince Alfred Hospital 1998 The department of neonatal medicine protocol bookjaundice Sydney Author Accessed May 2001 fromwwwcsnswgovaurpaneonatalhtmlnewprotjaund2htm
17 American Academy of Pediatrics (1994) Practice parameter Management ofhyperbilirubinemia in the healthy term newborn Pediatrics 94(4) 558-565) httpwwwaaporgpolicyhyperbhtm
18 International Lactation Consultant Association (1999) Evidence-Based Guidelines forBreastfeeding Management During the First Fourteen Days Raleigh NC Author
19 Mohrbacher N amp Stock J (1997) The Breastfeeding Answer Book Illinois La Leche League
20 Mills J amp Tudehope D (2001) The Cochrane Database of Systemic Reviews Fibreopticphototherapy for neonatal jaundice Volume (Issue 1)
21 Ludwig M (1990) Phototherapy in the home setting Journal of Pediatric Health Care 4(6)304-308
Jaundice in the Healthy Term Newborn
April 2002 Page 9 of 20
22 Hamelin K amp Seshia M (1998) Home phototherapy for uncomplicated neonatal jaundiceCanadian Nurse Jan 39-40
23 Murphy B amp Welch R (1992) Home phototherapy for the jaundiced full-term newbornJournal of Home Health Care Practitioner 5(1) 26-33
24 British Columbia Reproductive Care Program (2001) British Columbia Newborn Care PathOutcomes Teaching amp Interventions Vancouver Author
25 Campbell River Hospital (2000) Protocol Hyperbilirubinemia ndash Home PhototherapyManagement Campbell River BC Author
26 Mississauga Hospital (1994) Protocol Home Phototherapy Programme Mississauga ONAuthor
27 University of Manitoba Health Science Centre () Protocol Home Phototherapy ProgramWinnepeg Author Access from httpwwwumanitobacawomens_healthhschomethtm
WEB RESOURCES
httpwwwaaporgpolicyhyperbhtm
wwwcpscaenglishstatementsFNfn98-02htm
httpwwwcpscaenglishstatementsFNfn96-02htm
wwwcsnswgovaurpaneonatalhtmlnewprotjaund2htm
httpwwwumanitobacawomens_healthhschomethtm
Jaundice in the Healthy Term Newborn
April 2002 Page 10 of 20
Management of Newborn Jaundice at Home Program
Referral for the Healthy Term Infant
PHN Identifies jaundice in the newborn
1 Preterm Infant RhABO incompatibility2 Look or act ill (eg lethargic apnea tachycardia
temperature unstable poor feeding changed behaviorpersistant vomiting insufficient voidingstooling)
No
Family hx of early or severejaundice Ethnicity relevant(Mediterranean SE Asian)
No
Infant less than24 hrs
No
Is jaundiceclinically
significant
No
Jaundice persistedgt 2 weeks
Jaundice gt3weeks
Routinecare and
feedsNo
Routinecare and
feedsNo
RoutineClinical
Supervis-ion
No
Refer to MD ASAPYes
Refer to MD forinvestigationeg
G6PD SpherocytosisYes
Refer to MD fornon - isoimmune
hemolyticdisease
investigation
Yes
Refer to MD forfollow-up with total
serum bilirubinYes
Any abnormal physicalfindings Dark urine
light stoolsRefer to MDYes Yes
Refer to MDYes
APPENDIX 1 (Example)
Developed by the Coordinated Maternity Standards Committee South FraserHealth Region and Dr K Danso Pediatrician Surrey Memorial Hospital
Revised 1997 Copied with permission
Jaundice in the Healthy Term Newborn
April 2002 Page 11 of 20
APPENDIX 2
Approach to the Management of Hyperbilirubinemiain Term Newborn Infants
A Joint Statement with the College of Family Physicians of CanadaPaediatrics amp Child Health 19994(2)161-164Reference No FN98-02Reaffirmed February 2001
Reprints of this position statement are available from the Canadian Paediatric Society100-2204 Walkley Road Ottawa ON K1G 4G8 phone (613) 526-9397 fax (613) 526-3332
Contents bull Background bull Phototherapy bull Clinical management of hyperbilirubinemia in infants bull Exchange transfusion bull Conclusions bull References
Conflicting reports have led to confusion about the optimal management of jaundice in otherwise healthy terminfants (1-9) The lsquokinder gentler approachrsquo to neonatal hyperbilirubinemia proposed in 1992 by Newman andMaisels (8) resulted in a 1994 statement by the American Academy of Pediatrics (2) that addressed themanagement of healthy term infant without risk factors Recently there has been an increase in the number ofterm infants reported with kernicterus (10) It is important to note that while some of the infants reported withkernicterus had features that would place them in a high risk category some presented with severe jaundiceonly and no identifiable risk factors (10) The infants reported were commonly breastfed and frequentlydischarged from hospital very soon after birth (10) Nonetheless the current standards (2) for the managementof hyperbilirubinemia in the healthy term infant have become controversial This document updates information previously published by the Canadian Paediatric Society (1) It provides anoverview of the proposed management of hyperbilirubinemia based on available evidence even thoughrandomized controlled trials are not available to allow a conclusive assessment of the risk associated withhyperbilirubinemia in the clinical situations encountered in practice The objective of this overview is toestablish a management plan that will minimize the risk of kernicterus in term infants both with and withoutrisk factors Although scientific evidence has not established a clear link between specific bilirubinconcentrations and the development of kernicterus in healthy term babies information to date has beenincorporated into the following guidelines Background
Kernicterus is a neurological condition characterized by deep yellow staining of the basal nuclei Theaccompanying clinical syndrome results from the destructive changes of these neuronal populations Initiallythe signs are lethargy hypotonia and seizures later the infants may develop athetoid cerebral palsy mentalretardation and deafness When neurological signs evident in the infant permanent damage has alreadyoccurred leading to death or long term disability Therefore management strategies are aimed at preventingkernicterus
Jaundice in the Healthy Term Newborn
April 2002 Page 12 of 20
Until recently these strategies suggested maintaining serum unconjugated bilirubin concentrations below 340micromolL (20 mgdL) in healthy term infants through the use of phototherapy or exchange transfusion (11) Whileexchange transfusions had been a frequent occurrence from the 1950s to the 1970s and may sometimes still berequired phototherapy has become the mainstay of medical management of hyperbilirubinemia since that time
The cases of kernicterus originally described occurred mainly in infants with hemolytic disease Higher serumunconjugated bilirubin concentrations may be safe in healthy term infants without hemolytic disease It is notpossible to predict at what level an individual infant may develop kernicterus
Several authors have expressed serious concerns over the approach of allowing higher serum unconjugatedbilirubin concentrations to occur before investigating and treating these term infants (11-16) Brown andJohnson (10) have reported 23 cases of kernicterus occurring since 1989 16 in term and seven in near terminfants In these infants peak unconjugated bilirubin concentrations of 375 to 860 micromolL (22 to 50 mgdL)were seen All but one infant was breastfed Other associations found in these infants with kernicterus weredehydration (seven infants) glucose-6-phosphate dehydrogenase (G6PD) deficiency (five infants) ABOalloimmunization (one infant) hemolysis of unknown cause (five infants) familial etiology (one infant) andotherwise unexplained early jaundice clinically evident before 24 h of age (six infants) Similar cases have beenreported by others (1718) Although many of these babies were subsequently found to have additional riskfactors these factors were not often identified at the time the baby was noted to be jaundiced
Since the introduction in the 1990s of the kinder gentler approach to the management of hyperbilirubinemia agreat deal of confusion has arisen about approaches to the management of hyperbilirubinemia in healthy terminfants This confusion has extended to the care of borderline preterm infants who have often been treated asterm infants A recently published international survey reported considerable variability in the approach tohyperbilirubinemia and the use of phototherapy among neonatal units worldwide (3)
PhototherapyThe goal of hyperbilirubinemia treatment is to avoid bilirubin concentrations that may result in kernicterusPhototherapy remains an effective therapeutic intervention that decreases bilirubin concentrations therebypreventing elevated bilirubin levels associated with permanent sequelae
The effectiveness of phototherapy is related to the area of skin exposed and the radiant energy and thewavelength of the light (19-23) Phototherapy acts on unconjugated bilirubin to a depth of 2 mm from theepidermis Phototherapy changes the bilirubin through structural photoisomerization into water-solublelumirubin that is excreted in the urine (19) The fall in bilirubin level is proportionately greater in the skin thanin the serum (20) Therefore the infant receiving phototherapy should have as much skin as possible exposed tothe lights More intense phototherapy may be achieved by using multiple sources of phototherapy double ortriple phototherapy is recommended to optimize the skin surface exposed and therefore the efficacy ofphototherapy More detailed discussion of the physics of phototherapy has been published (124) It is important to recognize the relationship between dehydration and hyperbilirubinemia Dehydration may beassociated with increased serum bilirubin concentrations and may be exacerbated by phototherapy Alljaundiced infants should be adequately hydrated before and during phototherapy Breastfeeding is notcontraindicated in the presence of hyperbilirubinemia and should be continued More frequent breastfeedingsmay be beneficial (25)
The concentrations of bilirubin at which phototherapy might be initiated in healthy term infants and those withrisk factors are shown in Figure 1 Guidelines for phototherapy in low birth weight infants remain as previouslypublished (1) The bilirubin concentrations at which phototherapy is suggested by the Canadian PaediatricSociety in the present statement are more conservative than the current recommendations of the AmericanAcademy of Pediatrics (2) If the infant is a healthy term newborn phototherapy should be started as indicated
Jaundice in the Healthy Term Newborn
April 2002 Page 13 of 20
in the upper curve of Figure 1 If the infant has one or more risk factors a clinical decision should be made toinitiate phototherapy at the concentration indicated by the lower curve
Figure 1 Guidelines for initiation of phototherapy for hyperbilirubinemia in term infants with and without riskfactors Some risk factors include gestional age younger than 37 weeks birth weight less than 2500 ghemolysis jaundice at younger than 24 h of age sepsis and the need for resuscitation at birth
The timely recognition of risk factors is essential to minimize the danger of kernicterus The risk factors are asfollows
bull gestational age younger than 37 weeks and birth weight less than 2500 g bull hemolysis due to maternal isoimmunization G6PD deficiency spherocytosis or other causes bull jaundice at less than 24 h of age bull sepsis and bull the need for resuscitation at birth
Jaundice in the Healthy Term Newborn
April 2002 Page 14 of 20
Clinical management of hyperbilirubinemia in infants
A bilirubin level that justifies consideration of phototherapy should mandate the investigation of the cause ofhyperbilirubinemia Investigation should include a clinically pertinent history of the mother family historydescription of labour and delivery and infantrsquos clinical course (26) A physical examination should besupplemented by laboratory investigations (Table 1) including determination of unconjugated and conjugatedserum bilirubin concentrations and blood group with direct antibody test (Coombsrsquo test) and hemoglobin andhematocrit levels A complete blood count including differential white cell count and a blood smear for red cellmorphology may be indicated Further tests (eg reticulocyte count G6PD screen) may be indicated based oninitial results ethnicity or clinical presentation Testing for serum electrolytes and albumin or protein areindicated in some situations such as suspected dehydration or when bilirubin levels approach exchange valuesIn the absence of drugs or clinical states that alter the binding of bilirubin by albumin the bilirubin to albuminor the bilirubin to protein ratio reflects the free bilirubin concentration and the binding capacity of the serum(27-29) At a bilirubin concentration close to exchange transfusion levels some clinicians may wish to ensurethat serum bilirubin binding is normal (albumin 25 gL or greater protein 54 gL or greater) Values belowthese levels may be associated with low bilirubin binding and may be used by the clinician when decidingwhether further intervention (eg exchange transfusion) should take place (27)
TABLE 1 Laboratory investigation for hyperbilirubinemia in term newborn infants
Indicated (if bilirubin concentrations reach phototherapy levels) Serum total or unconjugated bilirubin concentration Serum conjugated bilirubin concentration Blood group with direct antibody test (Coombsrsquo test) Hemoglobin and hematocrit determinations
Optional (in specific clinical circumstances) Complete blood count including manual differential white cell count Blood smear for red cell morphology Reticulocyte count Glucose-6-phosphate dehydrogenase screen Serum electrolytes and albumin or protein concentrations
For infants with prolonged jaundice (lasting longer than seven days) or with conjugated hyperbilirubinemia(greater than 30 micromolL) additional investigation and management may be required and a consultation with aspecialist may be needed (30)
During the past decade most nurseries have shortened the time of hospital stay for term healthy newborninfants Early discharge of neonates means that jaundice is not often recognized at discharge (31) The CanadianPaediatric Society reiterates the importance of allowing early discharge only if a healthy status is confirmed foreach baby and appropriate follow-up is provided (32) Appropriate parental education about feeding signs ofdehydration and jaundice must be implemented in hospital nurseries Testing for serum bilirubin concentrationsmust be readily available for newborns on an out-patient basis Readmission to hospital (usually the hospital ofbirth) may be necessary for the investigation and management of hyperbilirubinemia
Exchange transfusion If phototherapy fails to control the rising bilirubin levels exchange transfusion is indicated to lower serumbilirubin concentrations For healthy term infants without risk factors exchange transfusion should beconsidered at serum unconjugated bilirubin concentrations of 400 to 430 micromolL For term infants with riskfactors the level should be 340 micromolL For infants who initially present with serum bilirubin concentrations in
Jaundice in the Healthy Term Newborn
April 2002 Page 15 of 20
excess of exchange levels intensive phototherapy should produce a decline of serum unconjugated bilirubinfrom 20 to 35 micromolL within 4 to 6 h and levels should continue to fall thereafter and remain below thethreshold for exchange transfusion If the bilirubin concentration does not decrease after adequate rehydrationand 4 to 6 h of intensive phototherapy exchange transfusion should be considered Preparation for thisincluding ensuring availability of blood should occur shortly after the admission of babies whose bilirubinconcentrations exceed exchange levels Appropriate consultation should be obtained if the etiology ofhyperbilirubinemia is unclear the infant is ill and particularly if bilirubin concentrations are approachingexchange levels Because the risks of exchange transfusion are significant the best management may bereviewed with an expert opinion from a neonatologist
Conclusions Hyperbilirubinemia in apparently healthy term newborn infants continues to hold the potential threat ofcomplications from bilirubin encephalopathy and kernicterus Careful assessment of risk factors judicious useof phototherapy appropriate laboratory monitoring and specific treatment of other disorders (eg sepsis) areessential for the optimal management of hyperbilirubinemia Appropriate laboratory facilities must be availableto measure bilirubin concentrations for out-patients in required clinical situations Readmission to hospital maybe required if phototherapy is necessary Guidelines for phototherapy are presented for term babies with andwithout identifiable risk factors
References
1 Fetus and Newborn Committee Canadian Paediatric Society Use of phototherapy for neonatalhyperbilirubinemia Can Med Assoc J 19861341237-45 2 American Academy of Pediatrics Practice parameter Management of hyperbilirubinemia in the healthy termnewborn Pediatrics 199494558-65 3 Hansen TWR Therapeutical approaches to neonatal jaundice an international survey Clin Pediatr199635309-16 4 Valaes T Koliopoulos C Koltsidopoulos A The impact of phototherapy in the management of neonatalhyperbilirubinemia comparison of historical cohorts Acta Paediatrica 199685273-6 5 Gustafson PA Boyle DW Bilirubin index a new standard for intervention Med Hypotheses 199545409-16 6 Torres-Torres M Tayaba R Weintraub A Holzman IR New perspectives on neonatal hyperbilirubinemiaMount Sinai J Med 199461424-8 7 Lazar L Litwin A Merlob P Phototherapy for neonatal nonhemolytic hyperbilirubinemia analysis ofrebound and indications for discontinuing therapy Clin Pediatr 199332264-7 8 Newman TB Maisels MJ Evaluation and treatment of jaundice in the term newborn Pediatrics 199289809-18 9 McMillan DD Lockyer JM Magnan L Akierman A Parboosingh JT Effect of educational program andinterview on adoption of guidelines for the management of neonatal hyperbilirubinemia Can Med Assoc J1991144707-12 10 Brown AK Johnson L Loss of concern about jaundice and the reemergence of kernicterus in full-terminfants in the era of managed care In Fanaroff AA Klaus MH eds The Year Book of Neonatal and PerinatalMedicine Philadelphia Mosby Yearbook 199617-28 11 Valaes T Bilirubin toxicity The problem was solved a generation ago Pediatrics 199289819-21 12 Wennberg RP Bilirubin recommendations present problems New guidelines simplistic and untestedPediatrics 199289821-2 13 Merenstein GB lsquoNewrsquo bilirubin recommendations questioned Pediatrics 199289822-3 14 Poland RL In search of a lsquogold standardrsquo for bilirubin toxicity Pediatrics 199289823-4 15 Brown AK Seidman DS Stevenson DK Jaundice in healthy term neonates Do we need new action levelsor new approaches Pediatrics 199289827-9 16 Johnson L Yet another expert opinion on bilirubin toxicity Pediatrics 199289829-31
Jaundice in the Healthy Term Newborn
April 2002 Page 16 of 20
17 MacDonald MG Hidden risks Early discharge and bilirubin toxicity due to glucose-6-phosphatedehydrogenase deficiency Pediatrics 199596734-8 18 Maisels MJ Newman TB Kernicterus in otherwise healthy breast-fed newborns Pediatrics 199596730-3 19 Vogl TP Phototherapy of neonatal hyperbilirubinemia bilirubin in unexposed areas of the skin J Pediatr197485707-1020 Rubaltelli FF Carli M The effect of light on cutaneous bilirubin Biol Neonate 197118457-62 21 Sisson TR Kendall N Shaw E et al Phototherapy of jaundice in the newborn infant 2 Effect of variouslight intensities J Pediatr 19738135-8 22 Bonta BW Warshaw JB Importance of radiant flux in the treatment of hyperbilirubinemia failure ofoverhead phototherapy units in intensive care units Pediatrics 197657502-5 23 Warshaw JB Gagliardi J Patel A A comparison of fluorescent and non-fluorescent light source forphototherapy Pediatrics 198065795-8 24 Ennever JF Blue light green light white light more light treatment of neonatal jaundice Clin Perinatol199017467-8125 Auerbach KG Gartner LM Breastfeeding and human milk their association with jaundice in the neonateClin Perinatol 19871489-108 26 Maisels MJ Jaundice in the newborn Pediatr Rev 19823305-20 27 Ahlfors CE Criteria for exchange transfusion in jaundiced newborns Pediatrics 199493488-94 28 Odell GB Storey GNB Rosenberg LA Studies in kernicterus III The saturation of serum protein withbilirubin during neonatal life and its relationship to brain damage at 5 years J Pediatr 19707612-21 29 Wirth FH Goldberg KE Lubchenco LO The neurologic outcome of infants evaluated for unboundbilirubin Pediatr Res 19759385-91 30 Haber BA Lake AM Cholestatic jaundice in the newborn Clin Perinatol 199017483-506 31 Maisels MJ Newman TB Jaundice in full-term and near-term babies who leave the hospital within 36hours The pediatricianrsquos nemesis Clin Perinatol 199825295-302 32 Fetus and Newborn Committee Canadian Paediatric Society and Society of Obstetricians andGynaecologists of Canada Facilitating discharge home following a normal term birth Paediatr Child Health19961165-8
Fetus and Newborn Committee Members Drs John Watts Department of Paediatrics Childrenrsquos Hospital ndash Hamilton Health Sciences CentreHamilton Ontario (director responsible) Douglas McMillan Department of Pediatrics Foothills HospitalCalgary Alberta (chair) Arne Ohlsson Department of Paediatrics Mount Sinai Hospital Toronto Ontario(co-chair) Deborah Davis Childrenrsquos Hospital of Eastern Ontario Ottawa Ontario Daniel Faucher RoyalVictoria Hospital Montreal Quebec (principal author) John Van Aerde Stollery Childrenrsquos Health CentreEdmonton Alberta Michael Vincer IWK-Grace Health Centre Halifax Nova ScotiaConsultant Dr Michael C Klein University of British Columbia Vancouver British Columbia (College ofFamily Physicians of Canada)Liaisons Drs James Lemon Riley Childrenrsquos Hospital Indiana University Medical Center IndianapolisIndiana (American Academy of Pediatrics) Saroj Saigal Department of Paediatrics McMaster UniversityMedical Centre Childrenrsquos Hospital ndash Hamilton Health Sciences Centre Hamilton Ontario (CPS Neonatal-Perinatal Medicine Section) Cheryl Levitt Department of Family Medicine Childrenrsquos Hospital ndash HamiltonHealth Sciences Centre Hamilton Ontario (College of Family Physicians of Canada) Catherine McCourtDirector Bureau of Reproductive amp Child Health Laboratory Centre for Disease Control Ottawa Ontario(Health Canada) Mrs Debbie Fraser-Askin Winnipeg Manitoba (Neonatal Nurses) Dr Line LeducDepartment of Obstetrics-Gynecology Hocircpital Sainte-Justine Montreal Quebec (Society of Obstetricians andGynaecologists of Canada)
Disclaimer The recommendations in this position statement do not indicate an exclusive course oftreatment or procedure to be followed Variations taking into account individual circumstances may beappropriate
Jaundice in the Healthy Term Newborn
April 2002 Page 17 of 20
APPENDIX 3Hyperbilirubinemia Risk Designation for Term and Near-Term Well Newborns
Jaundice in the Healthy Term Newborn
April 2002 Page 18 of 20
APPENDIX 4
American Academy of Pediatrics 1994 Practice parameter Management ofHyperbilirubinemia in the Healthy Term Newborn Pediatrics 94(4) 558-565
(Chart and Algorithm)
Jaundice in the Healthy Term Newborn
April 2002 Page 19 of 20
AlgorithmPediatric clinician evaluatesterm newborn with jaundice
Does the infant have signs of underlyingserious illness (lethargy apnea tachypneatemperature instability behavior changeshepatosplenomegaly persistant vomiting
or persistent feeding difficulty)
1
2
Exit this algorithm to individualizedclinical evaluation including
assessment of jaundice and underlyingdisease
Yes
3
No
Is the infant lt 37 weeks gestational age
4 Exit this algorithm to individualizedclinical evaluation including
assessment of jaundice in light ofprematurity
5
Yes
Is the mothersABO and Rh
blood typing andisoimmune
antibody screenstatus known
Is the mothersblood Rhpositive
Does themothers blood
have anyimmune
antibodies
Consider holding the infantscord blood in the blood bank incase future testing is necessary
6 7 8 9No
Yes Yes No
(Go to Box 10) (Go to Box 10) (Go to Box 10) (Go to Box 13)
No No Yes
Perform blood typing (ABO and Rh) and direct Coombs testingon the infants cord (preferably) or venous blood
10
Is the infantsblood direct
Coombs testpositive
Exit this algorithm to individualized clinical evaluationincluding assessment of jaundice and isoimmune
hemolytic disease
11 12
Yes
Are any of the following risk factors present tosuggest that nonisoimmune hemolytic disease
is possible in this infant(1) Family history of hemolytic anemia
OR(2) Family history of early or severe jaundice
OR(3) Ethnicity or geographic originassociated with hemolytic anemia
OR(4) Early or severe jaundice
Perform appropriate laboratoryassessment of infant including
(but not limited to consideration of)(1) Complete blood count differentialsmear reticulocyte count(2) G6PD screen(3) Hemoglobin electrophoresis
1314
No
No
No
(Go to Box 16)
Does the evaluation suggesthemolytic disease
15
Yes
(Go to Box 17)(Go to Box 16)
No
Jaundice in the Healthy Term Newborn
April 2002 Page 20 of 20
AlgorithmIs the infant
jaundiced andlt 24 hours of
age
Exit this algorithm to individualizedclinical evaluation includingassessment of jaundice and
nonisoimmune hemolytic disease
Is jaundiceclinicallysignificant by medical
judgment
(1) Measure infantstotal serum bilirubin(2) Go to Box 27
Healthy term infant with jaundice not clinicallysignificant by medical judgment
Follow infant in routine clinical supervision
1617
18 19
20
21
(Go to Box 22)
Yes
Yes
No
No
Is jaundicepersisting
gt 2 weeks
Does this infant haveabnormal physicalexam results dark
urine or light stools
Is jaundice persistinggt 3 weeks
Perform appropriate physical andlaboratory assessment of theinfant including possibility of
cholestatic jaundice
Provide routine carerecommend routine
feeding and follow-up Table 2 Management of Hyperbilirubinemia in the Healthy Term NewbornAgehours TSB Level mgdL (umolL)
Consider Phototherapy Exchange ExchangePhototherapy Transfusion Transfusion
if Intensive and IntensivePhototherapy PhototherapyFails
lt24 25-48 gt 12 (170) gt15 (260) gt 20 (340) gt 25 (430)49-72 gt 15 (260) gt 18 (310) gt 25 (430) gt 30 (510)gt 72 gt 17 (290) gt 20 (340) gt 25 (430) gt 30 (510)
TSB indicates total serum bilirubinPhototherapy at these TSB levels is a clinical option meaning that the intervention is availableand may be used on the basis of individual clinical judgement For a more detailed descriptionof phototherapy see the AppendixIntensive phototherapy (Appendix) should produce a decline of TSB of 1 to 2 mgdL within 4 to 6hours and the TSB level should continue to fall and remain below the threshold level for exchangetransfusion If this does not occur it is considered a failure of phototherapyTerm infants who are clinically jaundiced at lt 24 hours old are not considered healthy andrequire further evaluation (see text)
22 23
24
25
26
YesYes
No
YesNo
No 27
Algorithm Management of hyperbilirubinemia inthe healthy term infant
(From Box 19)
Jaundice in the Healthy Term Newborn
April 2002 Page 5 of 20
bull Elimination (See guide below)
Guide for Healthy Term Newborn Output
Day Number of Stools24 hours Number of Wet diapers24 hours
1 at least one meconium at least 1 2 at least one meconium at least 2 3 at least 1 transitional at least 3 4 at least 2 + yellowseedy at least 4 5 at least 2 + yellowseedy 5 - 6
See BCRCP British Columbia Newborn Care Path Outcomes Teaching amp Interventions document for norms27
V OTHER ILLNESS
In association with other findings jaundice may be a sign of serious illness Each jaundiced infantshould be assessed to see whether the following danger signs are present
bull Family history of significant hemolytic diseasebull Onset of jaundice within 24 hoursbull Pallor bruising petechiaebull Lethargybull Poor feedingbull Feverbull Vomitingbull Dark urine and light stoolsbull Hepatosplenomegalybull High pitched cry
CLINICAL MANAGEMENT
Clinical management is aimed at avoiding bilirubin encephalopathy with itrsquos long term neurologicalcomplications Adequate hydration is an important consideration in the infant with moderate to highbilirubin levels
Fundamental to management is a good history and physical examination together with appropriateinvestigations including
bull Unconjugated and conjugated bilirubinbull Blood group determination with a direct antibody test (Coombrsquos test)bull Hemoglobin and hematocritbull Other lab investigations (eg T4 G6PD) may be required depending on the patient assessment1
Once the serum bilirubin reaches ldquoriskrdquo levels11217 the standard treatment is the use of phototherapyandor exchange transfusion Several expert bodies have developed guidelines to assist care providers
Jaundice in the Healthy Term Newborn
April 2002 Page 6 of 20
determine the appropriate time to implement each therapy as well as how to provide the therapy mosteffectively11217
The most common guidelines utilized in risk identification and management of hyperbilirubinemia arelisted below
Appendix 2 Approach to the management of hyperbilirubinemia in term newborn infants1 A Joint Statement Canadian Paediatric Society amp College of Family
Physicians of Canada (February 2001) Appendix 3 Hyperbilirubinembia risk designation for term and near-term well newborns12 Bhutani at al (1999) Pediatrics Vol 103 No 1 p6-12
Appendix 4 Management of hyperbilirubinemia in healthy term newborns17 American Academy of Pediatrics (1994)
OTHER ISSUES IN THE MANAGEMENT OF JAUNDICE
I BREASTFEEDING AND PHOTOTHERAPY
bull Interruption of breastfeeding is usually not indicated6bull An adequate intake of milk minimizes the bilirubin level by stimulating bowel emptying
Encourage frequent and effective breastfeeding (as least 8X in 24 hours)618
bull Breastfeeding may be interrupted for diagnostic or therapeutic purposes when the bilirubin is highand there is the risk of an exchange transfusion Should this occurbull continue phototherapybull consider discontinuing breastfeeding for 24 hours or bull alternate breastfeeding with formula feeding if fluid intake is of concernbull offer positive support for breastfeeding Encourage maintenance of lactation by using a breast
pump or manual expression during the period of interrupted breastfeeding6bull Glucose water will not reduce serum bilirubin levels and may interfere with breastfeeding6 II DAYLIGHT TREATMENT
Exposing infants to indirect sunlight via a window to decrease bilirubin levels has been a longstanding practice19 Controlled studies on this treatment have not been done Mild jaundice requiresno sunlight exposure as it sends a false note to parents that their baby has a significant problem whenin fact (s)he has not If an infant has jaundice that needs treatment according to accepted guidelinesthen it should be investigated further
III FIBROPTIC PHOTOTHERAPY
Use of fibroptic or ldquobili blanketsrdquo is gaining increased interest A Cochrane Database Review20 foundthat fibroptic phototherapy was more effective at lowering serum bilirubin than no treatment but less
Jaundice in the Healthy Term Newborn
April 2002 Page 7 of 20
effective than conventional phototherapy A combination of fibroptic and conventional phototherapywas more effective than conventional phototherapy alone No conclusion could be made on thesuperiority of one fibroptic device over another No trials have been identified which support the viewthat fibroptic devices interfere less with infant care or impact less on parent-child bonding
At this time ldquobili blanketsrdquo should not be used alone to treat non-physiologic causes of jaundice orthose infants at risk of requiring an exchange transfusion
IV HOME PHOTOTHERAPY
There are few articles in the literature which address this issue21-24 With the advent of fibropticblankets and portable bilibeds home phototherapy has been implemented in a few communitiesthroughout Canada25-27 To date there are no published evidence-based guidelines on the use of homephototherapy
CLINICAL INDICATORS FOR EVALUATION
bull Serum bilirubin levels at which phototherapy is initiated (age specific in hours of life) bull Bilirubin levels at which the infant is readmitted bull Numbers of readmissions for jaundice
REFERENCES
1 Canadian Paediatric Society amp the College of Family Physicians of Canada (1999) Approach tothe management of hyperbilirubinemia in term newborn infants Paediatrics and Child Health 4(2)161-164 Access from wwwcpscaenglishstatementsFNfn98-02htm
2 Maisels J amp Newman T (1998) Jaundice in full-term and near-term babies who leave thehospital within 36 hours Clinics in Perinatology 25(2) 295-302
3 Maisels J amp Kring E (1998) Length of stay jaundice and hospital readmission Pediatrics101(6) 995-998
4 Gurpp-Phelan J Taylor J Liu L amp Davis R (1999) Early newborn hospital discharge andreadmission for mild and severe jaundice Archive of Pediatric and Adolescent Medicine 153 1283-1288)
5 Liu S Wen S McMillan D Trouton K Fowler D amp McCourt C (2000) Increasedneonatal readmission rate associated with decreased length of hospital stay at birth in CanadaCanadian Journal of Public Health 91(1) 46-50
6 American Academy of Pediatrics amp American College of Obstetricians and Gynecologists(1997) Guidelines for Perinatal Care (4rd Edition) American College of Obstetricians andGynecologists Elk Grove Village IL American Academy of Pediatrics Washington DC
7 Banks J Montgomer D Coody D amp Yetman R (1996) Hyperbilirubinemia in the termnewborn Journal of Pediatric Health Care 10(5) 228-230
Jaundice in the Healthy Term Newborn
April 2002 Page 8 of 20
8 Blackburn S (1995) Hyperbilirubinemia and neonatal jaundice Neonatal Network 14 (7)15-24
9 Canadian Paediatric Society amp the Society of Obstetricians and Gynaecologists of Canada (1996)Joint Policy Statement Facilitating discharge home following a normal term birth Paediatric amp ChildHealth1(2) 165-168Access from httpwwwcpscaenglishstatementsFNfn96-02htm
10 Bhutani V Gourley G Adler S Kreamer B Dalin C Johnson L (2000) NoninvasiveMeasurement of Total Bilirubin in a Multiracial Predischarge Newborn Population to Assess the Riskof Severe Hyperbilirubinemia Pediatrics (106) NO 2 Part 1 of 3
11 Schwoebel A amp Sakraida (1997) Hyperbilirubinemia New approaches to an old problemJournal of Perinatal and Neonatal Nursing 11(3) 78-97
12 Bhutani V Johnson L amp Sivieri E (1999) Predictive ability of a predischarge hour-specificserum bilirubin for subsequent significant hyperbilirubinemia in healthy term and near-term newbornsPediatrics 103(1) 6-14
13 Seidman D Ergaz Z Paz I Laor A Revel-Vilk S Stevenson D amp Gale R (1999)Predicting the risk of jaundice in fullterm healthy newborns A prospective population-based studyJournal of Perinatology 19(8) 564-567
14 Alpay F Sarici U Tosuncuk D Serdar M Inanc N amp Gokcay E (2000) The value offirst-day bilirubin measurement in predicting the development of significant hyperbilirubinemia inhealth term newborns Pediatrics 106(2)
15 Kramer L 1969 Advancement of dermal icterus in the jaundiced newborn American Journal ofDiseases in Children 118 454-458
16 Royal Prince Alfred Hospital 1998 The department of neonatal medicine protocol bookjaundice Sydney Author Accessed May 2001 fromwwwcsnswgovaurpaneonatalhtmlnewprotjaund2htm
17 American Academy of Pediatrics (1994) Practice parameter Management ofhyperbilirubinemia in the healthy term newborn Pediatrics 94(4) 558-565) httpwwwaaporgpolicyhyperbhtm
18 International Lactation Consultant Association (1999) Evidence-Based Guidelines forBreastfeeding Management During the First Fourteen Days Raleigh NC Author
19 Mohrbacher N amp Stock J (1997) The Breastfeeding Answer Book Illinois La Leche League
20 Mills J amp Tudehope D (2001) The Cochrane Database of Systemic Reviews Fibreopticphototherapy for neonatal jaundice Volume (Issue 1)
21 Ludwig M (1990) Phototherapy in the home setting Journal of Pediatric Health Care 4(6)304-308
Jaundice in the Healthy Term Newborn
April 2002 Page 9 of 20
22 Hamelin K amp Seshia M (1998) Home phototherapy for uncomplicated neonatal jaundiceCanadian Nurse Jan 39-40
23 Murphy B amp Welch R (1992) Home phototherapy for the jaundiced full-term newbornJournal of Home Health Care Practitioner 5(1) 26-33
24 British Columbia Reproductive Care Program (2001) British Columbia Newborn Care PathOutcomes Teaching amp Interventions Vancouver Author
25 Campbell River Hospital (2000) Protocol Hyperbilirubinemia ndash Home PhototherapyManagement Campbell River BC Author
26 Mississauga Hospital (1994) Protocol Home Phototherapy Programme Mississauga ONAuthor
27 University of Manitoba Health Science Centre () Protocol Home Phototherapy ProgramWinnepeg Author Access from httpwwwumanitobacawomens_healthhschomethtm
WEB RESOURCES
httpwwwaaporgpolicyhyperbhtm
wwwcpscaenglishstatementsFNfn98-02htm
httpwwwcpscaenglishstatementsFNfn96-02htm
wwwcsnswgovaurpaneonatalhtmlnewprotjaund2htm
httpwwwumanitobacawomens_healthhschomethtm
Jaundice in the Healthy Term Newborn
April 2002 Page 10 of 20
Management of Newborn Jaundice at Home Program
Referral for the Healthy Term Infant
PHN Identifies jaundice in the newborn
1 Preterm Infant RhABO incompatibility2 Look or act ill (eg lethargic apnea tachycardia
temperature unstable poor feeding changed behaviorpersistant vomiting insufficient voidingstooling)
No
Family hx of early or severejaundice Ethnicity relevant(Mediterranean SE Asian)
No
Infant less than24 hrs
No
Is jaundiceclinically
significant
No
Jaundice persistedgt 2 weeks
Jaundice gt3weeks
Routinecare and
feedsNo
Routinecare and
feedsNo
RoutineClinical
Supervis-ion
No
Refer to MD ASAPYes
Refer to MD forinvestigationeg
G6PD SpherocytosisYes
Refer to MD fornon - isoimmune
hemolyticdisease
investigation
Yes
Refer to MD forfollow-up with total
serum bilirubinYes
Any abnormal physicalfindings Dark urine
light stoolsRefer to MDYes Yes
Refer to MDYes
APPENDIX 1 (Example)
Developed by the Coordinated Maternity Standards Committee South FraserHealth Region and Dr K Danso Pediatrician Surrey Memorial Hospital
Revised 1997 Copied with permission
Jaundice in the Healthy Term Newborn
April 2002 Page 11 of 20
APPENDIX 2
Approach to the Management of Hyperbilirubinemiain Term Newborn Infants
A Joint Statement with the College of Family Physicians of CanadaPaediatrics amp Child Health 19994(2)161-164Reference No FN98-02Reaffirmed February 2001
Reprints of this position statement are available from the Canadian Paediatric Society100-2204 Walkley Road Ottawa ON K1G 4G8 phone (613) 526-9397 fax (613) 526-3332
Contents bull Background bull Phototherapy bull Clinical management of hyperbilirubinemia in infants bull Exchange transfusion bull Conclusions bull References
Conflicting reports have led to confusion about the optimal management of jaundice in otherwise healthy terminfants (1-9) The lsquokinder gentler approachrsquo to neonatal hyperbilirubinemia proposed in 1992 by Newman andMaisels (8) resulted in a 1994 statement by the American Academy of Pediatrics (2) that addressed themanagement of healthy term infant without risk factors Recently there has been an increase in the number ofterm infants reported with kernicterus (10) It is important to note that while some of the infants reported withkernicterus had features that would place them in a high risk category some presented with severe jaundiceonly and no identifiable risk factors (10) The infants reported were commonly breastfed and frequentlydischarged from hospital very soon after birth (10) Nonetheless the current standards (2) for the managementof hyperbilirubinemia in the healthy term infant have become controversial This document updates information previously published by the Canadian Paediatric Society (1) It provides anoverview of the proposed management of hyperbilirubinemia based on available evidence even thoughrandomized controlled trials are not available to allow a conclusive assessment of the risk associated withhyperbilirubinemia in the clinical situations encountered in practice The objective of this overview is toestablish a management plan that will minimize the risk of kernicterus in term infants both with and withoutrisk factors Although scientific evidence has not established a clear link between specific bilirubinconcentrations and the development of kernicterus in healthy term babies information to date has beenincorporated into the following guidelines Background
Kernicterus is a neurological condition characterized by deep yellow staining of the basal nuclei Theaccompanying clinical syndrome results from the destructive changes of these neuronal populations Initiallythe signs are lethargy hypotonia and seizures later the infants may develop athetoid cerebral palsy mentalretardation and deafness When neurological signs evident in the infant permanent damage has alreadyoccurred leading to death or long term disability Therefore management strategies are aimed at preventingkernicterus
Jaundice in the Healthy Term Newborn
April 2002 Page 12 of 20
Until recently these strategies suggested maintaining serum unconjugated bilirubin concentrations below 340micromolL (20 mgdL) in healthy term infants through the use of phototherapy or exchange transfusion (11) Whileexchange transfusions had been a frequent occurrence from the 1950s to the 1970s and may sometimes still berequired phototherapy has become the mainstay of medical management of hyperbilirubinemia since that time
The cases of kernicterus originally described occurred mainly in infants with hemolytic disease Higher serumunconjugated bilirubin concentrations may be safe in healthy term infants without hemolytic disease It is notpossible to predict at what level an individual infant may develop kernicterus
Several authors have expressed serious concerns over the approach of allowing higher serum unconjugatedbilirubin concentrations to occur before investigating and treating these term infants (11-16) Brown andJohnson (10) have reported 23 cases of kernicterus occurring since 1989 16 in term and seven in near terminfants In these infants peak unconjugated bilirubin concentrations of 375 to 860 micromolL (22 to 50 mgdL)were seen All but one infant was breastfed Other associations found in these infants with kernicterus weredehydration (seven infants) glucose-6-phosphate dehydrogenase (G6PD) deficiency (five infants) ABOalloimmunization (one infant) hemolysis of unknown cause (five infants) familial etiology (one infant) andotherwise unexplained early jaundice clinically evident before 24 h of age (six infants) Similar cases have beenreported by others (1718) Although many of these babies were subsequently found to have additional riskfactors these factors were not often identified at the time the baby was noted to be jaundiced
Since the introduction in the 1990s of the kinder gentler approach to the management of hyperbilirubinemia agreat deal of confusion has arisen about approaches to the management of hyperbilirubinemia in healthy terminfants This confusion has extended to the care of borderline preterm infants who have often been treated asterm infants A recently published international survey reported considerable variability in the approach tohyperbilirubinemia and the use of phototherapy among neonatal units worldwide (3)
PhototherapyThe goal of hyperbilirubinemia treatment is to avoid bilirubin concentrations that may result in kernicterusPhototherapy remains an effective therapeutic intervention that decreases bilirubin concentrations therebypreventing elevated bilirubin levels associated with permanent sequelae
The effectiveness of phototherapy is related to the area of skin exposed and the radiant energy and thewavelength of the light (19-23) Phototherapy acts on unconjugated bilirubin to a depth of 2 mm from theepidermis Phototherapy changes the bilirubin through structural photoisomerization into water-solublelumirubin that is excreted in the urine (19) The fall in bilirubin level is proportionately greater in the skin thanin the serum (20) Therefore the infant receiving phototherapy should have as much skin as possible exposed tothe lights More intense phototherapy may be achieved by using multiple sources of phototherapy double ortriple phototherapy is recommended to optimize the skin surface exposed and therefore the efficacy ofphototherapy More detailed discussion of the physics of phototherapy has been published (124) It is important to recognize the relationship between dehydration and hyperbilirubinemia Dehydration may beassociated with increased serum bilirubin concentrations and may be exacerbated by phototherapy Alljaundiced infants should be adequately hydrated before and during phototherapy Breastfeeding is notcontraindicated in the presence of hyperbilirubinemia and should be continued More frequent breastfeedingsmay be beneficial (25)
The concentrations of bilirubin at which phototherapy might be initiated in healthy term infants and those withrisk factors are shown in Figure 1 Guidelines for phototherapy in low birth weight infants remain as previouslypublished (1) The bilirubin concentrations at which phototherapy is suggested by the Canadian PaediatricSociety in the present statement are more conservative than the current recommendations of the AmericanAcademy of Pediatrics (2) If the infant is a healthy term newborn phototherapy should be started as indicated
Jaundice in the Healthy Term Newborn
April 2002 Page 13 of 20
in the upper curve of Figure 1 If the infant has one or more risk factors a clinical decision should be made toinitiate phototherapy at the concentration indicated by the lower curve
Figure 1 Guidelines for initiation of phototherapy for hyperbilirubinemia in term infants with and without riskfactors Some risk factors include gestional age younger than 37 weeks birth weight less than 2500 ghemolysis jaundice at younger than 24 h of age sepsis and the need for resuscitation at birth
The timely recognition of risk factors is essential to minimize the danger of kernicterus The risk factors are asfollows
bull gestational age younger than 37 weeks and birth weight less than 2500 g bull hemolysis due to maternal isoimmunization G6PD deficiency spherocytosis or other causes bull jaundice at less than 24 h of age bull sepsis and bull the need for resuscitation at birth
Jaundice in the Healthy Term Newborn
April 2002 Page 14 of 20
Clinical management of hyperbilirubinemia in infants
A bilirubin level that justifies consideration of phototherapy should mandate the investigation of the cause ofhyperbilirubinemia Investigation should include a clinically pertinent history of the mother family historydescription of labour and delivery and infantrsquos clinical course (26) A physical examination should besupplemented by laboratory investigations (Table 1) including determination of unconjugated and conjugatedserum bilirubin concentrations and blood group with direct antibody test (Coombsrsquo test) and hemoglobin andhematocrit levels A complete blood count including differential white cell count and a blood smear for red cellmorphology may be indicated Further tests (eg reticulocyte count G6PD screen) may be indicated based oninitial results ethnicity or clinical presentation Testing for serum electrolytes and albumin or protein areindicated in some situations such as suspected dehydration or when bilirubin levels approach exchange valuesIn the absence of drugs or clinical states that alter the binding of bilirubin by albumin the bilirubin to albuminor the bilirubin to protein ratio reflects the free bilirubin concentration and the binding capacity of the serum(27-29) At a bilirubin concentration close to exchange transfusion levels some clinicians may wish to ensurethat serum bilirubin binding is normal (albumin 25 gL or greater protein 54 gL or greater) Values belowthese levels may be associated with low bilirubin binding and may be used by the clinician when decidingwhether further intervention (eg exchange transfusion) should take place (27)
TABLE 1 Laboratory investigation for hyperbilirubinemia in term newborn infants
Indicated (if bilirubin concentrations reach phototherapy levels) Serum total or unconjugated bilirubin concentration Serum conjugated bilirubin concentration Blood group with direct antibody test (Coombsrsquo test) Hemoglobin and hematocrit determinations
Optional (in specific clinical circumstances) Complete blood count including manual differential white cell count Blood smear for red cell morphology Reticulocyte count Glucose-6-phosphate dehydrogenase screen Serum electrolytes and albumin or protein concentrations
For infants with prolonged jaundice (lasting longer than seven days) or with conjugated hyperbilirubinemia(greater than 30 micromolL) additional investigation and management may be required and a consultation with aspecialist may be needed (30)
During the past decade most nurseries have shortened the time of hospital stay for term healthy newborninfants Early discharge of neonates means that jaundice is not often recognized at discharge (31) The CanadianPaediatric Society reiterates the importance of allowing early discharge only if a healthy status is confirmed foreach baby and appropriate follow-up is provided (32) Appropriate parental education about feeding signs ofdehydration and jaundice must be implemented in hospital nurseries Testing for serum bilirubin concentrationsmust be readily available for newborns on an out-patient basis Readmission to hospital (usually the hospital ofbirth) may be necessary for the investigation and management of hyperbilirubinemia
Exchange transfusion If phototherapy fails to control the rising bilirubin levels exchange transfusion is indicated to lower serumbilirubin concentrations For healthy term infants without risk factors exchange transfusion should beconsidered at serum unconjugated bilirubin concentrations of 400 to 430 micromolL For term infants with riskfactors the level should be 340 micromolL For infants who initially present with serum bilirubin concentrations in
Jaundice in the Healthy Term Newborn
April 2002 Page 15 of 20
excess of exchange levels intensive phototherapy should produce a decline of serum unconjugated bilirubinfrom 20 to 35 micromolL within 4 to 6 h and levels should continue to fall thereafter and remain below thethreshold for exchange transfusion If the bilirubin concentration does not decrease after adequate rehydrationand 4 to 6 h of intensive phototherapy exchange transfusion should be considered Preparation for thisincluding ensuring availability of blood should occur shortly after the admission of babies whose bilirubinconcentrations exceed exchange levels Appropriate consultation should be obtained if the etiology ofhyperbilirubinemia is unclear the infant is ill and particularly if bilirubin concentrations are approachingexchange levels Because the risks of exchange transfusion are significant the best management may bereviewed with an expert opinion from a neonatologist
Conclusions Hyperbilirubinemia in apparently healthy term newborn infants continues to hold the potential threat ofcomplications from bilirubin encephalopathy and kernicterus Careful assessment of risk factors judicious useof phototherapy appropriate laboratory monitoring and specific treatment of other disorders (eg sepsis) areessential for the optimal management of hyperbilirubinemia Appropriate laboratory facilities must be availableto measure bilirubin concentrations for out-patients in required clinical situations Readmission to hospital maybe required if phototherapy is necessary Guidelines for phototherapy are presented for term babies with andwithout identifiable risk factors
References
1 Fetus and Newborn Committee Canadian Paediatric Society Use of phototherapy for neonatalhyperbilirubinemia Can Med Assoc J 19861341237-45 2 American Academy of Pediatrics Practice parameter Management of hyperbilirubinemia in the healthy termnewborn Pediatrics 199494558-65 3 Hansen TWR Therapeutical approaches to neonatal jaundice an international survey Clin Pediatr199635309-16 4 Valaes T Koliopoulos C Koltsidopoulos A The impact of phototherapy in the management of neonatalhyperbilirubinemia comparison of historical cohorts Acta Paediatrica 199685273-6 5 Gustafson PA Boyle DW Bilirubin index a new standard for intervention Med Hypotheses 199545409-16 6 Torres-Torres M Tayaba R Weintraub A Holzman IR New perspectives on neonatal hyperbilirubinemiaMount Sinai J Med 199461424-8 7 Lazar L Litwin A Merlob P Phototherapy for neonatal nonhemolytic hyperbilirubinemia analysis ofrebound and indications for discontinuing therapy Clin Pediatr 199332264-7 8 Newman TB Maisels MJ Evaluation and treatment of jaundice in the term newborn Pediatrics 199289809-18 9 McMillan DD Lockyer JM Magnan L Akierman A Parboosingh JT Effect of educational program andinterview on adoption of guidelines for the management of neonatal hyperbilirubinemia Can Med Assoc J1991144707-12 10 Brown AK Johnson L Loss of concern about jaundice and the reemergence of kernicterus in full-terminfants in the era of managed care In Fanaroff AA Klaus MH eds The Year Book of Neonatal and PerinatalMedicine Philadelphia Mosby Yearbook 199617-28 11 Valaes T Bilirubin toxicity The problem was solved a generation ago Pediatrics 199289819-21 12 Wennberg RP Bilirubin recommendations present problems New guidelines simplistic and untestedPediatrics 199289821-2 13 Merenstein GB lsquoNewrsquo bilirubin recommendations questioned Pediatrics 199289822-3 14 Poland RL In search of a lsquogold standardrsquo for bilirubin toxicity Pediatrics 199289823-4 15 Brown AK Seidman DS Stevenson DK Jaundice in healthy term neonates Do we need new action levelsor new approaches Pediatrics 199289827-9 16 Johnson L Yet another expert opinion on bilirubin toxicity Pediatrics 199289829-31
Jaundice in the Healthy Term Newborn
April 2002 Page 16 of 20
17 MacDonald MG Hidden risks Early discharge and bilirubin toxicity due to glucose-6-phosphatedehydrogenase deficiency Pediatrics 199596734-8 18 Maisels MJ Newman TB Kernicterus in otherwise healthy breast-fed newborns Pediatrics 199596730-3 19 Vogl TP Phototherapy of neonatal hyperbilirubinemia bilirubin in unexposed areas of the skin J Pediatr197485707-1020 Rubaltelli FF Carli M The effect of light on cutaneous bilirubin Biol Neonate 197118457-62 21 Sisson TR Kendall N Shaw E et al Phototherapy of jaundice in the newborn infant 2 Effect of variouslight intensities J Pediatr 19738135-8 22 Bonta BW Warshaw JB Importance of radiant flux in the treatment of hyperbilirubinemia failure ofoverhead phototherapy units in intensive care units Pediatrics 197657502-5 23 Warshaw JB Gagliardi J Patel A A comparison of fluorescent and non-fluorescent light source forphototherapy Pediatrics 198065795-8 24 Ennever JF Blue light green light white light more light treatment of neonatal jaundice Clin Perinatol199017467-8125 Auerbach KG Gartner LM Breastfeeding and human milk their association with jaundice in the neonateClin Perinatol 19871489-108 26 Maisels MJ Jaundice in the newborn Pediatr Rev 19823305-20 27 Ahlfors CE Criteria for exchange transfusion in jaundiced newborns Pediatrics 199493488-94 28 Odell GB Storey GNB Rosenberg LA Studies in kernicterus III The saturation of serum protein withbilirubin during neonatal life and its relationship to brain damage at 5 years J Pediatr 19707612-21 29 Wirth FH Goldberg KE Lubchenco LO The neurologic outcome of infants evaluated for unboundbilirubin Pediatr Res 19759385-91 30 Haber BA Lake AM Cholestatic jaundice in the newborn Clin Perinatol 199017483-506 31 Maisels MJ Newman TB Jaundice in full-term and near-term babies who leave the hospital within 36hours The pediatricianrsquos nemesis Clin Perinatol 199825295-302 32 Fetus and Newborn Committee Canadian Paediatric Society and Society of Obstetricians andGynaecologists of Canada Facilitating discharge home following a normal term birth Paediatr Child Health19961165-8
Fetus and Newborn Committee Members Drs John Watts Department of Paediatrics Childrenrsquos Hospital ndash Hamilton Health Sciences CentreHamilton Ontario (director responsible) Douglas McMillan Department of Pediatrics Foothills HospitalCalgary Alberta (chair) Arne Ohlsson Department of Paediatrics Mount Sinai Hospital Toronto Ontario(co-chair) Deborah Davis Childrenrsquos Hospital of Eastern Ontario Ottawa Ontario Daniel Faucher RoyalVictoria Hospital Montreal Quebec (principal author) John Van Aerde Stollery Childrenrsquos Health CentreEdmonton Alberta Michael Vincer IWK-Grace Health Centre Halifax Nova ScotiaConsultant Dr Michael C Klein University of British Columbia Vancouver British Columbia (College ofFamily Physicians of Canada)Liaisons Drs James Lemon Riley Childrenrsquos Hospital Indiana University Medical Center IndianapolisIndiana (American Academy of Pediatrics) Saroj Saigal Department of Paediatrics McMaster UniversityMedical Centre Childrenrsquos Hospital ndash Hamilton Health Sciences Centre Hamilton Ontario (CPS Neonatal-Perinatal Medicine Section) Cheryl Levitt Department of Family Medicine Childrenrsquos Hospital ndash HamiltonHealth Sciences Centre Hamilton Ontario (College of Family Physicians of Canada) Catherine McCourtDirector Bureau of Reproductive amp Child Health Laboratory Centre for Disease Control Ottawa Ontario(Health Canada) Mrs Debbie Fraser-Askin Winnipeg Manitoba (Neonatal Nurses) Dr Line LeducDepartment of Obstetrics-Gynecology Hocircpital Sainte-Justine Montreal Quebec (Society of Obstetricians andGynaecologists of Canada)
Disclaimer The recommendations in this position statement do not indicate an exclusive course oftreatment or procedure to be followed Variations taking into account individual circumstances may beappropriate
Jaundice in the Healthy Term Newborn
April 2002 Page 17 of 20
APPENDIX 3Hyperbilirubinemia Risk Designation for Term and Near-Term Well Newborns
Jaundice in the Healthy Term Newborn
April 2002 Page 18 of 20
APPENDIX 4
American Academy of Pediatrics 1994 Practice parameter Management ofHyperbilirubinemia in the Healthy Term Newborn Pediatrics 94(4) 558-565
(Chart and Algorithm)
Jaundice in the Healthy Term Newborn
April 2002 Page 19 of 20
AlgorithmPediatric clinician evaluatesterm newborn with jaundice
Does the infant have signs of underlyingserious illness (lethargy apnea tachypneatemperature instability behavior changeshepatosplenomegaly persistant vomiting
or persistent feeding difficulty)
1
2
Exit this algorithm to individualizedclinical evaluation including
assessment of jaundice and underlyingdisease
Yes
3
No
Is the infant lt 37 weeks gestational age
4 Exit this algorithm to individualizedclinical evaluation including
assessment of jaundice in light ofprematurity
5
Yes
Is the mothersABO and Rh
blood typing andisoimmune
antibody screenstatus known
Is the mothersblood Rhpositive
Does themothers blood
have anyimmune
antibodies
Consider holding the infantscord blood in the blood bank incase future testing is necessary
6 7 8 9No
Yes Yes No
(Go to Box 10) (Go to Box 10) (Go to Box 10) (Go to Box 13)
No No Yes
Perform blood typing (ABO and Rh) and direct Coombs testingon the infants cord (preferably) or venous blood
10
Is the infantsblood direct
Coombs testpositive
Exit this algorithm to individualized clinical evaluationincluding assessment of jaundice and isoimmune
hemolytic disease
11 12
Yes
Are any of the following risk factors present tosuggest that nonisoimmune hemolytic disease
is possible in this infant(1) Family history of hemolytic anemia
OR(2) Family history of early or severe jaundice
OR(3) Ethnicity or geographic originassociated with hemolytic anemia
OR(4) Early or severe jaundice
Perform appropriate laboratoryassessment of infant including
(but not limited to consideration of)(1) Complete blood count differentialsmear reticulocyte count(2) G6PD screen(3) Hemoglobin electrophoresis
1314
No
No
No
(Go to Box 16)
Does the evaluation suggesthemolytic disease
15
Yes
(Go to Box 17)(Go to Box 16)
No
Jaundice in the Healthy Term Newborn
April 2002 Page 20 of 20
AlgorithmIs the infant
jaundiced andlt 24 hours of
age
Exit this algorithm to individualizedclinical evaluation includingassessment of jaundice and
nonisoimmune hemolytic disease
Is jaundiceclinicallysignificant by medical
judgment
(1) Measure infantstotal serum bilirubin(2) Go to Box 27
Healthy term infant with jaundice not clinicallysignificant by medical judgment
Follow infant in routine clinical supervision
1617
18 19
20
21
(Go to Box 22)
Yes
Yes
No
No
Is jaundicepersisting
gt 2 weeks
Does this infant haveabnormal physicalexam results dark
urine or light stools
Is jaundice persistinggt 3 weeks
Perform appropriate physical andlaboratory assessment of theinfant including possibility of
cholestatic jaundice
Provide routine carerecommend routine
feeding and follow-up Table 2 Management of Hyperbilirubinemia in the Healthy Term NewbornAgehours TSB Level mgdL (umolL)
Consider Phototherapy Exchange ExchangePhototherapy Transfusion Transfusion
if Intensive and IntensivePhototherapy PhototherapyFails
lt24 25-48 gt 12 (170) gt15 (260) gt 20 (340) gt 25 (430)49-72 gt 15 (260) gt 18 (310) gt 25 (430) gt 30 (510)gt 72 gt 17 (290) gt 20 (340) gt 25 (430) gt 30 (510)
TSB indicates total serum bilirubinPhototherapy at these TSB levels is a clinical option meaning that the intervention is availableand may be used on the basis of individual clinical judgement For a more detailed descriptionof phototherapy see the AppendixIntensive phototherapy (Appendix) should produce a decline of TSB of 1 to 2 mgdL within 4 to 6hours and the TSB level should continue to fall and remain below the threshold level for exchangetransfusion If this does not occur it is considered a failure of phototherapyTerm infants who are clinically jaundiced at lt 24 hours old are not considered healthy andrequire further evaluation (see text)
22 23
24
25
26
YesYes
No
YesNo
No 27
Algorithm Management of hyperbilirubinemia inthe healthy term infant
(From Box 19)
Jaundice in the Healthy Term Newborn
April 2002 Page 6 of 20
determine the appropriate time to implement each therapy as well as how to provide the therapy mosteffectively11217
The most common guidelines utilized in risk identification and management of hyperbilirubinemia arelisted below
Appendix 2 Approach to the management of hyperbilirubinemia in term newborn infants1 A Joint Statement Canadian Paediatric Society amp College of Family
Physicians of Canada (February 2001) Appendix 3 Hyperbilirubinembia risk designation for term and near-term well newborns12 Bhutani at al (1999) Pediatrics Vol 103 No 1 p6-12
Appendix 4 Management of hyperbilirubinemia in healthy term newborns17 American Academy of Pediatrics (1994)
OTHER ISSUES IN THE MANAGEMENT OF JAUNDICE
I BREASTFEEDING AND PHOTOTHERAPY
bull Interruption of breastfeeding is usually not indicated6bull An adequate intake of milk minimizes the bilirubin level by stimulating bowel emptying
Encourage frequent and effective breastfeeding (as least 8X in 24 hours)618
bull Breastfeeding may be interrupted for diagnostic or therapeutic purposes when the bilirubin is highand there is the risk of an exchange transfusion Should this occurbull continue phototherapybull consider discontinuing breastfeeding for 24 hours or bull alternate breastfeeding with formula feeding if fluid intake is of concernbull offer positive support for breastfeeding Encourage maintenance of lactation by using a breast
pump or manual expression during the period of interrupted breastfeeding6bull Glucose water will not reduce serum bilirubin levels and may interfere with breastfeeding6 II DAYLIGHT TREATMENT
Exposing infants to indirect sunlight via a window to decrease bilirubin levels has been a longstanding practice19 Controlled studies on this treatment have not been done Mild jaundice requiresno sunlight exposure as it sends a false note to parents that their baby has a significant problem whenin fact (s)he has not If an infant has jaundice that needs treatment according to accepted guidelinesthen it should be investigated further
III FIBROPTIC PHOTOTHERAPY
Use of fibroptic or ldquobili blanketsrdquo is gaining increased interest A Cochrane Database Review20 foundthat fibroptic phototherapy was more effective at lowering serum bilirubin than no treatment but less
Jaundice in the Healthy Term Newborn
April 2002 Page 7 of 20
effective than conventional phototherapy A combination of fibroptic and conventional phototherapywas more effective than conventional phototherapy alone No conclusion could be made on thesuperiority of one fibroptic device over another No trials have been identified which support the viewthat fibroptic devices interfere less with infant care or impact less on parent-child bonding
At this time ldquobili blanketsrdquo should not be used alone to treat non-physiologic causes of jaundice orthose infants at risk of requiring an exchange transfusion
IV HOME PHOTOTHERAPY
There are few articles in the literature which address this issue21-24 With the advent of fibropticblankets and portable bilibeds home phototherapy has been implemented in a few communitiesthroughout Canada25-27 To date there are no published evidence-based guidelines on the use of homephototherapy
CLINICAL INDICATORS FOR EVALUATION
bull Serum bilirubin levels at which phototherapy is initiated (age specific in hours of life) bull Bilirubin levels at which the infant is readmitted bull Numbers of readmissions for jaundice
REFERENCES
1 Canadian Paediatric Society amp the College of Family Physicians of Canada (1999) Approach tothe management of hyperbilirubinemia in term newborn infants Paediatrics and Child Health 4(2)161-164 Access from wwwcpscaenglishstatementsFNfn98-02htm
2 Maisels J amp Newman T (1998) Jaundice in full-term and near-term babies who leave thehospital within 36 hours Clinics in Perinatology 25(2) 295-302
3 Maisels J amp Kring E (1998) Length of stay jaundice and hospital readmission Pediatrics101(6) 995-998
4 Gurpp-Phelan J Taylor J Liu L amp Davis R (1999) Early newborn hospital discharge andreadmission for mild and severe jaundice Archive of Pediatric and Adolescent Medicine 153 1283-1288)
5 Liu S Wen S McMillan D Trouton K Fowler D amp McCourt C (2000) Increasedneonatal readmission rate associated with decreased length of hospital stay at birth in CanadaCanadian Journal of Public Health 91(1) 46-50
6 American Academy of Pediatrics amp American College of Obstetricians and Gynecologists(1997) Guidelines for Perinatal Care (4rd Edition) American College of Obstetricians andGynecologists Elk Grove Village IL American Academy of Pediatrics Washington DC
7 Banks J Montgomer D Coody D amp Yetman R (1996) Hyperbilirubinemia in the termnewborn Journal of Pediatric Health Care 10(5) 228-230
Jaundice in the Healthy Term Newborn
April 2002 Page 8 of 20
8 Blackburn S (1995) Hyperbilirubinemia and neonatal jaundice Neonatal Network 14 (7)15-24
9 Canadian Paediatric Society amp the Society of Obstetricians and Gynaecologists of Canada (1996)Joint Policy Statement Facilitating discharge home following a normal term birth Paediatric amp ChildHealth1(2) 165-168Access from httpwwwcpscaenglishstatementsFNfn96-02htm
10 Bhutani V Gourley G Adler S Kreamer B Dalin C Johnson L (2000) NoninvasiveMeasurement of Total Bilirubin in a Multiracial Predischarge Newborn Population to Assess the Riskof Severe Hyperbilirubinemia Pediatrics (106) NO 2 Part 1 of 3
11 Schwoebel A amp Sakraida (1997) Hyperbilirubinemia New approaches to an old problemJournal of Perinatal and Neonatal Nursing 11(3) 78-97
12 Bhutani V Johnson L amp Sivieri E (1999) Predictive ability of a predischarge hour-specificserum bilirubin for subsequent significant hyperbilirubinemia in healthy term and near-term newbornsPediatrics 103(1) 6-14
13 Seidman D Ergaz Z Paz I Laor A Revel-Vilk S Stevenson D amp Gale R (1999)Predicting the risk of jaundice in fullterm healthy newborns A prospective population-based studyJournal of Perinatology 19(8) 564-567
14 Alpay F Sarici U Tosuncuk D Serdar M Inanc N amp Gokcay E (2000) The value offirst-day bilirubin measurement in predicting the development of significant hyperbilirubinemia inhealth term newborns Pediatrics 106(2)
15 Kramer L 1969 Advancement of dermal icterus in the jaundiced newborn American Journal ofDiseases in Children 118 454-458
16 Royal Prince Alfred Hospital 1998 The department of neonatal medicine protocol bookjaundice Sydney Author Accessed May 2001 fromwwwcsnswgovaurpaneonatalhtmlnewprotjaund2htm
17 American Academy of Pediatrics (1994) Practice parameter Management ofhyperbilirubinemia in the healthy term newborn Pediatrics 94(4) 558-565) httpwwwaaporgpolicyhyperbhtm
18 International Lactation Consultant Association (1999) Evidence-Based Guidelines forBreastfeeding Management During the First Fourteen Days Raleigh NC Author
19 Mohrbacher N amp Stock J (1997) The Breastfeeding Answer Book Illinois La Leche League
20 Mills J amp Tudehope D (2001) The Cochrane Database of Systemic Reviews Fibreopticphototherapy for neonatal jaundice Volume (Issue 1)
21 Ludwig M (1990) Phototherapy in the home setting Journal of Pediatric Health Care 4(6)304-308
Jaundice in the Healthy Term Newborn
April 2002 Page 9 of 20
22 Hamelin K amp Seshia M (1998) Home phototherapy for uncomplicated neonatal jaundiceCanadian Nurse Jan 39-40
23 Murphy B amp Welch R (1992) Home phototherapy for the jaundiced full-term newbornJournal of Home Health Care Practitioner 5(1) 26-33
24 British Columbia Reproductive Care Program (2001) British Columbia Newborn Care PathOutcomes Teaching amp Interventions Vancouver Author
25 Campbell River Hospital (2000) Protocol Hyperbilirubinemia ndash Home PhototherapyManagement Campbell River BC Author
26 Mississauga Hospital (1994) Protocol Home Phototherapy Programme Mississauga ONAuthor
27 University of Manitoba Health Science Centre () Protocol Home Phototherapy ProgramWinnepeg Author Access from httpwwwumanitobacawomens_healthhschomethtm
WEB RESOURCES
httpwwwaaporgpolicyhyperbhtm
wwwcpscaenglishstatementsFNfn98-02htm
httpwwwcpscaenglishstatementsFNfn96-02htm
wwwcsnswgovaurpaneonatalhtmlnewprotjaund2htm
httpwwwumanitobacawomens_healthhschomethtm
Jaundice in the Healthy Term Newborn
April 2002 Page 10 of 20
Management of Newborn Jaundice at Home Program
Referral for the Healthy Term Infant
PHN Identifies jaundice in the newborn
1 Preterm Infant RhABO incompatibility2 Look or act ill (eg lethargic apnea tachycardia
temperature unstable poor feeding changed behaviorpersistant vomiting insufficient voidingstooling)
No
Family hx of early or severejaundice Ethnicity relevant(Mediterranean SE Asian)
No
Infant less than24 hrs
No
Is jaundiceclinically
significant
No
Jaundice persistedgt 2 weeks
Jaundice gt3weeks
Routinecare and
feedsNo
Routinecare and
feedsNo
RoutineClinical
Supervis-ion
No
Refer to MD ASAPYes
Refer to MD forinvestigationeg
G6PD SpherocytosisYes
Refer to MD fornon - isoimmune
hemolyticdisease
investigation
Yes
Refer to MD forfollow-up with total
serum bilirubinYes
Any abnormal physicalfindings Dark urine
light stoolsRefer to MDYes Yes
Refer to MDYes
APPENDIX 1 (Example)
Developed by the Coordinated Maternity Standards Committee South FraserHealth Region and Dr K Danso Pediatrician Surrey Memorial Hospital
Revised 1997 Copied with permission
Jaundice in the Healthy Term Newborn
April 2002 Page 11 of 20
APPENDIX 2
Approach to the Management of Hyperbilirubinemiain Term Newborn Infants
A Joint Statement with the College of Family Physicians of CanadaPaediatrics amp Child Health 19994(2)161-164Reference No FN98-02Reaffirmed February 2001
Reprints of this position statement are available from the Canadian Paediatric Society100-2204 Walkley Road Ottawa ON K1G 4G8 phone (613) 526-9397 fax (613) 526-3332
Contents bull Background bull Phototherapy bull Clinical management of hyperbilirubinemia in infants bull Exchange transfusion bull Conclusions bull References
Conflicting reports have led to confusion about the optimal management of jaundice in otherwise healthy terminfants (1-9) The lsquokinder gentler approachrsquo to neonatal hyperbilirubinemia proposed in 1992 by Newman andMaisels (8) resulted in a 1994 statement by the American Academy of Pediatrics (2) that addressed themanagement of healthy term infant without risk factors Recently there has been an increase in the number ofterm infants reported with kernicterus (10) It is important to note that while some of the infants reported withkernicterus had features that would place them in a high risk category some presented with severe jaundiceonly and no identifiable risk factors (10) The infants reported were commonly breastfed and frequentlydischarged from hospital very soon after birth (10) Nonetheless the current standards (2) for the managementof hyperbilirubinemia in the healthy term infant have become controversial This document updates information previously published by the Canadian Paediatric Society (1) It provides anoverview of the proposed management of hyperbilirubinemia based on available evidence even thoughrandomized controlled trials are not available to allow a conclusive assessment of the risk associated withhyperbilirubinemia in the clinical situations encountered in practice The objective of this overview is toestablish a management plan that will minimize the risk of kernicterus in term infants both with and withoutrisk factors Although scientific evidence has not established a clear link between specific bilirubinconcentrations and the development of kernicterus in healthy term babies information to date has beenincorporated into the following guidelines Background
Kernicterus is a neurological condition characterized by deep yellow staining of the basal nuclei Theaccompanying clinical syndrome results from the destructive changes of these neuronal populations Initiallythe signs are lethargy hypotonia and seizures later the infants may develop athetoid cerebral palsy mentalretardation and deafness When neurological signs evident in the infant permanent damage has alreadyoccurred leading to death or long term disability Therefore management strategies are aimed at preventingkernicterus
Jaundice in the Healthy Term Newborn
April 2002 Page 12 of 20
Until recently these strategies suggested maintaining serum unconjugated bilirubin concentrations below 340micromolL (20 mgdL) in healthy term infants through the use of phototherapy or exchange transfusion (11) Whileexchange transfusions had been a frequent occurrence from the 1950s to the 1970s and may sometimes still berequired phototherapy has become the mainstay of medical management of hyperbilirubinemia since that time
The cases of kernicterus originally described occurred mainly in infants with hemolytic disease Higher serumunconjugated bilirubin concentrations may be safe in healthy term infants without hemolytic disease It is notpossible to predict at what level an individual infant may develop kernicterus
Several authors have expressed serious concerns over the approach of allowing higher serum unconjugatedbilirubin concentrations to occur before investigating and treating these term infants (11-16) Brown andJohnson (10) have reported 23 cases of kernicterus occurring since 1989 16 in term and seven in near terminfants In these infants peak unconjugated bilirubin concentrations of 375 to 860 micromolL (22 to 50 mgdL)were seen All but one infant was breastfed Other associations found in these infants with kernicterus weredehydration (seven infants) glucose-6-phosphate dehydrogenase (G6PD) deficiency (five infants) ABOalloimmunization (one infant) hemolysis of unknown cause (five infants) familial etiology (one infant) andotherwise unexplained early jaundice clinically evident before 24 h of age (six infants) Similar cases have beenreported by others (1718) Although many of these babies were subsequently found to have additional riskfactors these factors were not often identified at the time the baby was noted to be jaundiced
Since the introduction in the 1990s of the kinder gentler approach to the management of hyperbilirubinemia agreat deal of confusion has arisen about approaches to the management of hyperbilirubinemia in healthy terminfants This confusion has extended to the care of borderline preterm infants who have often been treated asterm infants A recently published international survey reported considerable variability in the approach tohyperbilirubinemia and the use of phototherapy among neonatal units worldwide (3)
PhototherapyThe goal of hyperbilirubinemia treatment is to avoid bilirubin concentrations that may result in kernicterusPhototherapy remains an effective therapeutic intervention that decreases bilirubin concentrations therebypreventing elevated bilirubin levels associated with permanent sequelae
The effectiveness of phototherapy is related to the area of skin exposed and the radiant energy and thewavelength of the light (19-23) Phototherapy acts on unconjugated bilirubin to a depth of 2 mm from theepidermis Phototherapy changes the bilirubin through structural photoisomerization into water-solublelumirubin that is excreted in the urine (19) The fall in bilirubin level is proportionately greater in the skin thanin the serum (20) Therefore the infant receiving phototherapy should have as much skin as possible exposed tothe lights More intense phototherapy may be achieved by using multiple sources of phototherapy double ortriple phototherapy is recommended to optimize the skin surface exposed and therefore the efficacy ofphototherapy More detailed discussion of the physics of phototherapy has been published (124) It is important to recognize the relationship between dehydration and hyperbilirubinemia Dehydration may beassociated with increased serum bilirubin concentrations and may be exacerbated by phototherapy Alljaundiced infants should be adequately hydrated before and during phototherapy Breastfeeding is notcontraindicated in the presence of hyperbilirubinemia and should be continued More frequent breastfeedingsmay be beneficial (25)
The concentrations of bilirubin at which phototherapy might be initiated in healthy term infants and those withrisk factors are shown in Figure 1 Guidelines for phototherapy in low birth weight infants remain as previouslypublished (1) The bilirubin concentrations at which phototherapy is suggested by the Canadian PaediatricSociety in the present statement are more conservative than the current recommendations of the AmericanAcademy of Pediatrics (2) If the infant is a healthy term newborn phototherapy should be started as indicated
Jaundice in the Healthy Term Newborn
April 2002 Page 13 of 20
in the upper curve of Figure 1 If the infant has one or more risk factors a clinical decision should be made toinitiate phototherapy at the concentration indicated by the lower curve
Figure 1 Guidelines for initiation of phototherapy for hyperbilirubinemia in term infants with and without riskfactors Some risk factors include gestional age younger than 37 weeks birth weight less than 2500 ghemolysis jaundice at younger than 24 h of age sepsis and the need for resuscitation at birth
The timely recognition of risk factors is essential to minimize the danger of kernicterus The risk factors are asfollows
bull gestational age younger than 37 weeks and birth weight less than 2500 g bull hemolysis due to maternal isoimmunization G6PD deficiency spherocytosis or other causes bull jaundice at less than 24 h of age bull sepsis and bull the need for resuscitation at birth
Jaundice in the Healthy Term Newborn
April 2002 Page 14 of 20
Clinical management of hyperbilirubinemia in infants
A bilirubin level that justifies consideration of phototherapy should mandate the investigation of the cause ofhyperbilirubinemia Investigation should include a clinically pertinent history of the mother family historydescription of labour and delivery and infantrsquos clinical course (26) A physical examination should besupplemented by laboratory investigations (Table 1) including determination of unconjugated and conjugatedserum bilirubin concentrations and blood group with direct antibody test (Coombsrsquo test) and hemoglobin andhematocrit levels A complete blood count including differential white cell count and a blood smear for red cellmorphology may be indicated Further tests (eg reticulocyte count G6PD screen) may be indicated based oninitial results ethnicity or clinical presentation Testing for serum electrolytes and albumin or protein areindicated in some situations such as suspected dehydration or when bilirubin levels approach exchange valuesIn the absence of drugs or clinical states that alter the binding of bilirubin by albumin the bilirubin to albuminor the bilirubin to protein ratio reflects the free bilirubin concentration and the binding capacity of the serum(27-29) At a bilirubin concentration close to exchange transfusion levels some clinicians may wish to ensurethat serum bilirubin binding is normal (albumin 25 gL or greater protein 54 gL or greater) Values belowthese levels may be associated with low bilirubin binding and may be used by the clinician when decidingwhether further intervention (eg exchange transfusion) should take place (27)
TABLE 1 Laboratory investigation for hyperbilirubinemia in term newborn infants
Indicated (if bilirubin concentrations reach phototherapy levels) Serum total or unconjugated bilirubin concentration Serum conjugated bilirubin concentration Blood group with direct antibody test (Coombsrsquo test) Hemoglobin and hematocrit determinations
Optional (in specific clinical circumstances) Complete blood count including manual differential white cell count Blood smear for red cell morphology Reticulocyte count Glucose-6-phosphate dehydrogenase screen Serum electrolytes and albumin or protein concentrations
For infants with prolonged jaundice (lasting longer than seven days) or with conjugated hyperbilirubinemia(greater than 30 micromolL) additional investigation and management may be required and a consultation with aspecialist may be needed (30)
During the past decade most nurseries have shortened the time of hospital stay for term healthy newborninfants Early discharge of neonates means that jaundice is not often recognized at discharge (31) The CanadianPaediatric Society reiterates the importance of allowing early discharge only if a healthy status is confirmed foreach baby and appropriate follow-up is provided (32) Appropriate parental education about feeding signs ofdehydration and jaundice must be implemented in hospital nurseries Testing for serum bilirubin concentrationsmust be readily available for newborns on an out-patient basis Readmission to hospital (usually the hospital ofbirth) may be necessary for the investigation and management of hyperbilirubinemia
Exchange transfusion If phototherapy fails to control the rising bilirubin levels exchange transfusion is indicated to lower serumbilirubin concentrations For healthy term infants without risk factors exchange transfusion should beconsidered at serum unconjugated bilirubin concentrations of 400 to 430 micromolL For term infants with riskfactors the level should be 340 micromolL For infants who initially present with serum bilirubin concentrations in
Jaundice in the Healthy Term Newborn
April 2002 Page 15 of 20
excess of exchange levels intensive phototherapy should produce a decline of serum unconjugated bilirubinfrom 20 to 35 micromolL within 4 to 6 h and levels should continue to fall thereafter and remain below thethreshold for exchange transfusion If the bilirubin concentration does not decrease after adequate rehydrationand 4 to 6 h of intensive phototherapy exchange transfusion should be considered Preparation for thisincluding ensuring availability of blood should occur shortly after the admission of babies whose bilirubinconcentrations exceed exchange levels Appropriate consultation should be obtained if the etiology ofhyperbilirubinemia is unclear the infant is ill and particularly if bilirubin concentrations are approachingexchange levels Because the risks of exchange transfusion are significant the best management may bereviewed with an expert opinion from a neonatologist
Conclusions Hyperbilirubinemia in apparently healthy term newborn infants continues to hold the potential threat ofcomplications from bilirubin encephalopathy and kernicterus Careful assessment of risk factors judicious useof phototherapy appropriate laboratory monitoring and specific treatment of other disorders (eg sepsis) areessential for the optimal management of hyperbilirubinemia Appropriate laboratory facilities must be availableto measure bilirubin concentrations for out-patients in required clinical situations Readmission to hospital maybe required if phototherapy is necessary Guidelines for phototherapy are presented for term babies with andwithout identifiable risk factors
References
1 Fetus and Newborn Committee Canadian Paediatric Society Use of phototherapy for neonatalhyperbilirubinemia Can Med Assoc J 19861341237-45 2 American Academy of Pediatrics Practice parameter Management of hyperbilirubinemia in the healthy termnewborn Pediatrics 199494558-65 3 Hansen TWR Therapeutical approaches to neonatal jaundice an international survey Clin Pediatr199635309-16 4 Valaes T Koliopoulos C Koltsidopoulos A The impact of phototherapy in the management of neonatalhyperbilirubinemia comparison of historical cohorts Acta Paediatrica 199685273-6 5 Gustafson PA Boyle DW Bilirubin index a new standard for intervention Med Hypotheses 199545409-16 6 Torres-Torres M Tayaba R Weintraub A Holzman IR New perspectives on neonatal hyperbilirubinemiaMount Sinai J Med 199461424-8 7 Lazar L Litwin A Merlob P Phototherapy for neonatal nonhemolytic hyperbilirubinemia analysis ofrebound and indications for discontinuing therapy Clin Pediatr 199332264-7 8 Newman TB Maisels MJ Evaluation and treatment of jaundice in the term newborn Pediatrics 199289809-18 9 McMillan DD Lockyer JM Magnan L Akierman A Parboosingh JT Effect of educational program andinterview on adoption of guidelines for the management of neonatal hyperbilirubinemia Can Med Assoc J1991144707-12 10 Brown AK Johnson L Loss of concern about jaundice and the reemergence of kernicterus in full-terminfants in the era of managed care In Fanaroff AA Klaus MH eds The Year Book of Neonatal and PerinatalMedicine Philadelphia Mosby Yearbook 199617-28 11 Valaes T Bilirubin toxicity The problem was solved a generation ago Pediatrics 199289819-21 12 Wennberg RP Bilirubin recommendations present problems New guidelines simplistic and untestedPediatrics 199289821-2 13 Merenstein GB lsquoNewrsquo bilirubin recommendations questioned Pediatrics 199289822-3 14 Poland RL In search of a lsquogold standardrsquo for bilirubin toxicity Pediatrics 199289823-4 15 Brown AK Seidman DS Stevenson DK Jaundice in healthy term neonates Do we need new action levelsor new approaches Pediatrics 199289827-9 16 Johnson L Yet another expert opinion on bilirubin toxicity Pediatrics 199289829-31
Jaundice in the Healthy Term Newborn
April 2002 Page 16 of 20
17 MacDonald MG Hidden risks Early discharge and bilirubin toxicity due to glucose-6-phosphatedehydrogenase deficiency Pediatrics 199596734-8 18 Maisels MJ Newman TB Kernicterus in otherwise healthy breast-fed newborns Pediatrics 199596730-3 19 Vogl TP Phototherapy of neonatal hyperbilirubinemia bilirubin in unexposed areas of the skin J Pediatr197485707-1020 Rubaltelli FF Carli M The effect of light on cutaneous bilirubin Biol Neonate 197118457-62 21 Sisson TR Kendall N Shaw E et al Phototherapy of jaundice in the newborn infant 2 Effect of variouslight intensities J Pediatr 19738135-8 22 Bonta BW Warshaw JB Importance of radiant flux in the treatment of hyperbilirubinemia failure ofoverhead phototherapy units in intensive care units Pediatrics 197657502-5 23 Warshaw JB Gagliardi J Patel A A comparison of fluorescent and non-fluorescent light source forphototherapy Pediatrics 198065795-8 24 Ennever JF Blue light green light white light more light treatment of neonatal jaundice Clin Perinatol199017467-8125 Auerbach KG Gartner LM Breastfeeding and human milk their association with jaundice in the neonateClin Perinatol 19871489-108 26 Maisels MJ Jaundice in the newborn Pediatr Rev 19823305-20 27 Ahlfors CE Criteria for exchange transfusion in jaundiced newborns Pediatrics 199493488-94 28 Odell GB Storey GNB Rosenberg LA Studies in kernicterus III The saturation of serum protein withbilirubin during neonatal life and its relationship to brain damage at 5 years J Pediatr 19707612-21 29 Wirth FH Goldberg KE Lubchenco LO The neurologic outcome of infants evaluated for unboundbilirubin Pediatr Res 19759385-91 30 Haber BA Lake AM Cholestatic jaundice in the newborn Clin Perinatol 199017483-506 31 Maisels MJ Newman TB Jaundice in full-term and near-term babies who leave the hospital within 36hours The pediatricianrsquos nemesis Clin Perinatol 199825295-302 32 Fetus and Newborn Committee Canadian Paediatric Society and Society of Obstetricians andGynaecologists of Canada Facilitating discharge home following a normal term birth Paediatr Child Health19961165-8
Fetus and Newborn Committee Members Drs John Watts Department of Paediatrics Childrenrsquos Hospital ndash Hamilton Health Sciences CentreHamilton Ontario (director responsible) Douglas McMillan Department of Pediatrics Foothills HospitalCalgary Alberta (chair) Arne Ohlsson Department of Paediatrics Mount Sinai Hospital Toronto Ontario(co-chair) Deborah Davis Childrenrsquos Hospital of Eastern Ontario Ottawa Ontario Daniel Faucher RoyalVictoria Hospital Montreal Quebec (principal author) John Van Aerde Stollery Childrenrsquos Health CentreEdmonton Alberta Michael Vincer IWK-Grace Health Centre Halifax Nova ScotiaConsultant Dr Michael C Klein University of British Columbia Vancouver British Columbia (College ofFamily Physicians of Canada)Liaisons Drs James Lemon Riley Childrenrsquos Hospital Indiana University Medical Center IndianapolisIndiana (American Academy of Pediatrics) Saroj Saigal Department of Paediatrics McMaster UniversityMedical Centre Childrenrsquos Hospital ndash Hamilton Health Sciences Centre Hamilton Ontario (CPS Neonatal-Perinatal Medicine Section) Cheryl Levitt Department of Family Medicine Childrenrsquos Hospital ndash HamiltonHealth Sciences Centre Hamilton Ontario (College of Family Physicians of Canada) Catherine McCourtDirector Bureau of Reproductive amp Child Health Laboratory Centre for Disease Control Ottawa Ontario(Health Canada) Mrs Debbie Fraser-Askin Winnipeg Manitoba (Neonatal Nurses) Dr Line LeducDepartment of Obstetrics-Gynecology Hocircpital Sainte-Justine Montreal Quebec (Society of Obstetricians andGynaecologists of Canada)
Disclaimer The recommendations in this position statement do not indicate an exclusive course oftreatment or procedure to be followed Variations taking into account individual circumstances may beappropriate
Jaundice in the Healthy Term Newborn
April 2002 Page 17 of 20
APPENDIX 3Hyperbilirubinemia Risk Designation for Term and Near-Term Well Newborns
Jaundice in the Healthy Term Newborn
April 2002 Page 18 of 20
APPENDIX 4
American Academy of Pediatrics 1994 Practice parameter Management ofHyperbilirubinemia in the Healthy Term Newborn Pediatrics 94(4) 558-565
(Chart and Algorithm)
Jaundice in the Healthy Term Newborn
April 2002 Page 19 of 20
AlgorithmPediatric clinician evaluatesterm newborn with jaundice
Does the infant have signs of underlyingserious illness (lethargy apnea tachypneatemperature instability behavior changeshepatosplenomegaly persistant vomiting
or persistent feeding difficulty)
1
2
Exit this algorithm to individualizedclinical evaluation including
assessment of jaundice and underlyingdisease
Yes
3
No
Is the infant lt 37 weeks gestational age
4 Exit this algorithm to individualizedclinical evaluation including
assessment of jaundice in light ofprematurity
5
Yes
Is the mothersABO and Rh
blood typing andisoimmune
antibody screenstatus known
Is the mothersblood Rhpositive
Does themothers blood
have anyimmune
antibodies
Consider holding the infantscord blood in the blood bank incase future testing is necessary
6 7 8 9No
Yes Yes No
(Go to Box 10) (Go to Box 10) (Go to Box 10) (Go to Box 13)
No No Yes
Perform blood typing (ABO and Rh) and direct Coombs testingon the infants cord (preferably) or venous blood
10
Is the infantsblood direct
Coombs testpositive
Exit this algorithm to individualized clinical evaluationincluding assessment of jaundice and isoimmune
hemolytic disease
11 12
Yes
Are any of the following risk factors present tosuggest that nonisoimmune hemolytic disease
is possible in this infant(1) Family history of hemolytic anemia
OR(2) Family history of early or severe jaundice
OR(3) Ethnicity or geographic originassociated with hemolytic anemia
OR(4) Early or severe jaundice
Perform appropriate laboratoryassessment of infant including
(but not limited to consideration of)(1) Complete blood count differentialsmear reticulocyte count(2) G6PD screen(3) Hemoglobin electrophoresis
1314
No
No
No
(Go to Box 16)
Does the evaluation suggesthemolytic disease
15
Yes
(Go to Box 17)(Go to Box 16)
No
Jaundice in the Healthy Term Newborn
April 2002 Page 20 of 20
AlgorithmIs the infant
jaundiced andlt 24 hours of
age
Exit this algorithm to individualizedclinical evaluation includingassessment of jaundice and
nonisoimmune hemolytic disease
Is jaundiceclinicallysignificant by medical
judgment
(1) Measure infantstotal serum bilirubin(2) Go to Box 27
Healthy term infant with jaundice not clinicallysignificant by medical judgment
Follow infant in routine clinical supervision
1617
18 19
20
21
(Go to Box 22)
Yes
Yes
No
No
Is jaundicepersisting
gt 2 weeks
Does this infant haveabnormal physicalexam results dark
urine or light stools
Is jaundice persistinggt 3 weeks
Perform appropriate physical andlaboratory assessment of theinfant including possibility of
cholestatic jaundice
Provide routine carerecommend routine
feeding and follow-up Table 2 Management of Hyperbilirubinemia in the Healthy Term NewbornAgehours TSB Level mgdL (umolL)
Consider Phototherapy Exchange ExchangePhototherapy Transfusion Transfusion
if Intensive and IntensivePhototherapy PhototherapyFails
lt24 25-48 gt 12 (170) gt15 (260) gt 20 (340) gt 25 (430)49-72 gt 15 (260) gt 18 (310) gt 25 (430) gt 30 (510)gt 72 gt 17 (290) gt 20 (340) gt 25 (430) gt 30 (510)
TSB indicates total serum bilirubinPhototherapy at these TSB levels is a clinical option meaning that the intervention is availableand may be used on the basis of individual clinical judgement For a more detailed descriptionof phototherapy see the AppendixIntensive phototherapy (Appendix) should produce a decline of TSB of 1 to 2 mgdL within 4 to 6hours and the TSB level should continue to fall and remain below the threshold level for exchangetransfusion If this does not occur it is considered a failure of phototherapyTerm infants who are clinically jaundiced at lt 24 hours old are not considered healthy andrequire further evaluation (see text)
22 23
24
25
26
YesYes
No
YesNo
No 27
Algorithm Management of hyperbilirubinemia inthe healthy term infant
(From Box 19)
Jaundice in the Healthy Term Newborn
April 2002 Page 7 of 20
effective than conventional phototherapy A combination of fibroptic and conventional phototherapywas more effective than conventional phototherapy alone No conclusion could be made on thesuperiority of one fibroptic device over another No trials have been identified which support the viewthat fibroptic devices interfere less with infant care or impact less on parent-child bonding
At this time ldquobili blanketsrdquo should not be used alone to treat non-physiologic causes of jaundice orthose infants at risk of requiring an exchange transfusion
IV HOME PHOTOTHERAPY
There are few articles in the literature which address this issue21-24 With the advent of fibropticblankets and portable bilibeds home phototherapy has been implemented in a few communitiesthroughout Canada25-27 To date there are no published evidence-based guidelines on the use of homephototherapy
CLINICAL INDICATORS FOR EVALUATION
bull Serum bilirubin levels at which phototherapy is initiated (age specific in hours of life) bull Bilirubin levels at which the infant is readmitted bull Numbers of readmissions for jaundice
REFERENCES
1 Canadian Paediatric Society amp the College of Family Physicians of Canada (1999) Approach tothe management of hyperbilirubinemia in term newborn infants Paediatrics and Child Health 4(2)161-164 Access from wwwcpscaenglishstatementsFNfn98-02htm
2 Maisels J amp Newman T (1998) Jaundice in full-term and near-term babies who leave thehospital within 36 hours Clinics in Perinatology 25(2) 295-302
3 Maisels J amp Kring E (1998) Length of stay jaundice and hospital readmission Pediatrics101(6) 995-998
4 Gurpp-Phelan J Taylor J Liu L amp Davis R (1999) Early newborn hospital discharge andreadmission for mild and severe jaundice Archive of Pediatric and Adolescent Medicine 153 1283-1288)
5 Liu S Wen S McMillan D Trouton K Fowler D amp McCourt C (2000) Increasedneonatal readmission rate associated with decreased length of hospital stay at birth in CanadaCanadian Journal of Public Health 91(1) 46-50
6 American Academy of Pediatrics amp American College of Obstetricians and Gynecologists(1997) Guidelines for Perinatal Care (4rd Edition) American College of Obstetricians andGynecologists Elk Grove Village IL American Academy of Pediatrics Washington DC
7 Banks J Montgomer D Coody D amp Yetman R (1996) Hyperbilirubinemia in the termnewborn Journal of Pediatric Health Care 10(5) 228-230
Jaundice in the Healthy Term Newborn
April 2002 Page 8 of 20
8 Blackburn S (1995) Hyperbilirubinemia and neonatal jaundice Neonatal Network 14 (7)15-24
9 Canadian Paediatric Society amp the Society of Obstetricians and Gynaecologists of Canada (1996)Joint Policy Statement Facilitating discharge home following a normal term birth Paediatric amp ChildHealth1(2) 165-168Access from httpwwwcpscaenglishstatementsFNfn96-02htm
10 Bhutani V Gourley G Adler S Kreamer B Dalin C Johnson L (2000) NoninvasiveMeasurement of Total Bilirubin in a Multiracial Predischarge Newborn Population to Assess the Riskof Severe Hyperbilirubinemia Pediatrics (106) NO 2 Part 1 of 3
11 Schwoebel A amp Sakraida (1997) Hyperbilirubinemia New approaches to an old problemJournal of Perinatal and Neonatal Nursing 11(3) 78-97
12 Bhutani V Johnson L amp Sivieri E (1999) Predictive ability of a predischarge hour-specificserum bilirubin for subsequent significant hyperbilirubinemia in healthy term and near-term newbornsPediatrics 103(1) 6-14
13 Seidman D Ergaz Z Paz I Laor A Revel-Vilk S Stevenson D amp Gale R (1999)Predicting the risk of jaundice in fullterm healthy newborns A prospective population-based studyJournal of Perinatology 19(8) 564-567
14 Alpay F Sarici U Tosuncuk D Serdar M Inanc N amp Gokcay E (2000) The value offirst-day bilirubin measurement in predicting the development of significant hyperbilirubinemia inhealth term newborns Pediatrics 106(2)
15 Kramer L 1969 Advancement of dermal icterus in the jaundiced newborn American Journal ofDiseases in Children 118 454-458
16 Royal Prince Alfred Hospital 1998 The department of neonatal medicine protocol bookjaundice Sydney Author Accessed May 2001 fromwwwcsnswgovaurpaneonatalhtmlnewprotjaund2htm
17 American Academy of Pediatrics (1994) Practice parameter Management ofhyperbilirubinemia in the healthy term newborn Pediatrics 94(4) 558-565) httpwwwaaporgpolicyhyperbhtm
18 International Lactation Consultant Association (1999) Evidence-Based Guidelines forBreastfeeding Management During the First Fourteen Days Raleigh NC Author
19 Mohrbacher N amp Stock J (1997) The Breastfeeding Answer Book Illinois La Leche League
20 Mills J amp Tudehope D (2001) The Cochrane Database of Systemic Reviews Fibreopticphototherapy for neonatal jaundice Volume (Issue 1)
21 Ludwig M (1990) Phototherapy in the home setting Journal of Pediatric Health Care 4(6)304-308
Jaundice in the Healthy Term Newborn
April 2002 Page 9 of 20
22 Hamelin K amp Seshia M (1998) Home phototherapy for uncomplicated neonatal jaundiceCanadian Nurse Jan 39-40
23 Murphy B amp Welch R (1992) Home phototherapy for the jaundiced full-term newbornJournal of Home Health Care Practitioner 5(1) 26-33
24 British Columbia Reproductive Care Program (2001) British Columbia Newborn Care PathOutcomes Teaching amp Interventions Vancouver Author
25 Campbell River Hospital (2000) Protocol Hyperbilirubinemia ndash Home PhototherapyManagement Campbell River BC Author
26 Mississauga Hospital (1994) Protocol Home Phototherapy Programme Mississauga ONAuthor
27 University of Manitoba Health Science Centre () Protocol Home Phototherapy ProgramWinnepeg Author Access from httpwwwumanitobacawomens_healthhschomethtm
WEB RESOURCES
httpwwwaaporgpolicyhyperbhtm
wwwcpscaenglishstatementsFNfn98-02htm
httpwwwcpscaenglishstatementsFNfn96-02htm
wwwcsnswgovaurpaneonatalhtmlnewprotjaund2htm
httpwwwumanitobacawomens_healthhschomethtm
Jaundice in the Healthy Term Newborn
April 2002 Page 10 of 20
Management of Newborn Jaundice at Home Program
Referral for the Healthy Term Infant
PHN Identifies jaundice in the newborn
1 Preterm Infant RhABO incompatibility2 Look or act ill (eg lethargic apnea tachycardia
temperature unstable poor feeding changed behaviorpersistant vomiting insufficient voidingstooling)
No
Family hx of early or severejaundice Ethnicity relevant(Mediterranean SE Asian)
No
Infant less than24 hrs
No
Is jaundiceclinically
significant
No
Jaundice persistedgt 2 weeks
Jaundice gt3weeks
Routinecare and
feedsNo
Routinecare and
feedsNo
RoutineClinical
Supervis-ion
No
Refer to MD ASAPYes
Refer to MD forinvestigationeg
G6PD SpherocytosisYes
Refer to MD fornon - isoimmune
hemolyticdisease
investigation
Yes
Refer to MD forfollow-up with total
serum bilirubinYes
Any abnormal physicalfindings Dark urine
light stoolsRefer to MDYes Yes
Refer to MDYes
APPENDIX 1 (Example)
Developed by the Coordinated Maternity Standards Committee South FraserHealth Region and Dr K Danso Pediatrician Surrey Memorial Hospital
Revised 1997 Copied with permission
Jaundice in the Healthy Term Newborn
April 2002 Page 11 of 20
APPENDIX 2
Approach to the Management of Hyperbilirubinemiain Term Newborn Infants
A Joint Statement with the College of Family Physicians of CanadaPaediatrics amp Child Health 19994(2)161-164Reference No FN98-02Reaffirmed February 2001
Reprints of this position statement are available from the Canadian Paediatric Society100-2204 Walkley Road Ottawa ON K1G 4G8 phone (613) 526-9397 fax (613) 526-3332
Contents bull Background bull Phototherapy bull Clinical management of hyperbilirubinemia in infants bull Exchange transfusion bull Conclusions bull References
Conflicting reports have led to confusion about the optimal management of jaundice in otherwise healthy terminfants (1-9) The lsquokinder gentler approachrsquo to neonatal hyperbilirubinemia proposed in 1992 by Newman andMaisels (8) resulted in a 1994 statement by the American Academy of Pediatrics (2) that addressed themanagement of healthy term infant without risk factors Recently there has been an increase in the number ofterm infants reported with kernicterus (10) It is important to note that while some of the infants reported withkernicterus had features that would place them in a high risk category some presented with severe jaundiceonly and no identifiable risk factors (10) The infants reported were commonly breastfed and frequentlydischarged from hospital very soon after birth (10) Nonetheless the current standards (2) for the managementof hyperbilirubinemia in the healthy term infant have become controversial This document updates information previously published by the Canadian Paediatric Society (1) It provides anoverview of the proposed management of hyperbilirubinemia based on available evidence even thoughrandomized controlled trials are not available to allow a conclusive assessment of the risk associated withhyperbilirubinemia in the clinical situations encountered in practice The objective of this overview is toestablish a management plan that will minimize the risk of kernicterus in term infants both with and withoutrisk factors Although scientific evidence has not established a clear link between specific bilirubinconcentrations and the development of kernicterus in healthy term babies information to date has beenincorporated into the following guidelines Background
Kernicterus is a neurological condition characterized by deep yellow staining of the basal nuclei Theaccompanying clinical syndrome results from the destructive changes of these neuronal populations Initiallythe signs are lethargy hypotonia and seizures later the infants may develop athetoid cerebral palsy mentalretardation and deafness When neurological signs evident in the infant permanent damage has alreadyoccurred leading to death or long term disability Therefore management strategies are aimed at preventingkernicterus
Jaundice in the Healthy Term Newborn
April 2002 Page 12 of 20
Until recently these strategies suggested maintaining serum unconjugated bilirubin concentrations below 340micromolL (20 mgdL) in healthy term infants through the use of phototherapy or exchange transfusion (11) Whileexchange transfusions had been a frequent occurrence from the 1950s to the 1970s and may sometimes still berequired phototherapy has become the mainstay of medical management of hyperbilirubinemia since that time
The cases of kernicterus originally described occurred mainly in infants with hemolytic disease Higher serumunconjugated bilirubin concentrations may be safe in healthy term infants without hemolytic disease It is notpossible to predict at what level an individual infant may develop kernicterus
Several authors have expressed serious concerns over the approach of allowing higher serum unconjugatedbilirubin concentrations to occur before investigating and treating these term infants (11-16) Brown andJohnson (10) have reported 23 cases of kernicterus occurring since 1989 16 in term and seven in near terminfants In these infants peak unconjugated bilirubin concentrations of 375 to 860 micromolL (22 to 50 mgdL)were seen All but one infant was breastfed Other associations found in these infants with kernicterus weredehydration (seven infants) glucose-6-phosphate dehydrogenase (G6PD) deficiency (five infants) ABOalloimmunization (one infant) hemolysis of unknown cause (five infants) familial etiology (one infant) andotherwise unexplained early jaundice clinically evident before 24 h of age (six infants) Similar cases have beenreported by others (1718) Although many of these babies were subsequently found to have additional riskfactors these factors were not often identified at the time the baby was noted to be jaundiced
Since the introduction in the 1990s of the kinder gentler approach to the management of hyperbilirubinemia agreat deal of confusion has arisen about approaches to the management of hyperbilirubinemia in healthy terminfants This confusion has extended to the care of borderline preterm infants who have often been treated asterm infants A recently published international survey reported considerable variability in the approach tohyperbilirubinemia and the use of phototherapy among neonatal units worldwide (3)
PhototherapyThe goal of hyperbilirubinemia treatment is to avoid bilirubin concentrations that may result in kernicterusPhototherapy remains an effective therapeutic intervention that decreases bilirubin concentrations therebypreventing elevated bilirubin levels associated with permanent sequelae
The effectiveness of phototherapy is related to the area of skin exposed and the radiant energy and thewavelength of the light (19-23) Phototherapy acts on unconjugated bilirubin to a depth of 2 mm from theepidermis Phototherapy changes the bilirubin through structural photoisomerization into water-solublelumirubin that is excreted in the urine (19) The fall in bilirubin level is proportionately greater in the skin thanin the serum (20) Therefore the infant receiving phototherapy should have as much skin as possible exposed tothe lights More intense phototherapy may be achieved by using multiple sources of phototherapy double ortriple phototherapy is recommended to optimize the skin surface exposed and therefore the efficacy ofphototherapy More detailed discussion of the physics of phototherapy has been published (124) It is important to recognize the relationship between dehydration and hyperbilirubinemia Dehydration may beassociated with increased serum bilirubin concentrations and may be exacerbated by phototherapy Alljaundiced infants should be adequately hydrated before and during phototherapy Breastfeeding is notcontraindicated in the presence of hyperbilirubinemia and should be continued More frequent breastfeedingsmay be beneficial (25)
The concentrations of bilirubin at which phototherapy might be initiated in healthy term infants and those withrisk factors are shown in Figure 1 Guidelines for phototherapy in low birth weight infants remain as previouslypublished (1) The bilirubin concentrations at which phototherapy is suggested by the Canadian PaediatricSociety in the present statement are more conservative than the current recommendations of the AmericanAcademy of Pediatrics (2) If the infant is a healthy term newborn phototherapy should be started as indicated
Jaundice in the Healthy Term Newborn
April 2002 Page 13 of 20
in the upper curve of Figure 1 If the infant has one or more risk factors a clinical decision should be made toinitiate phototherapy at the concentration indicated by the lower curve
Figure 1 Guidelines for initiation of phototherapy for hyperbilirubinemia in term infants with and without riskfactors Some risk factors include gestional age younger than 37 weeks birth weight less than 2500 ghemolysis jaundice at younger than 24 h of age sepsis and the need for resuscitation at birth
The timely recognition of risk factors is essential to minimize the danger of kernicterus The risk factors are asfollows
bull gestational age younger than 37 weeks and birth weight less than 2500 g bull hemolysis due to maternal isoimmunization G6PD deficiency spherocytosis or other causes bull jaundice at less than 24 h of age bull sepsis and bull the need for resuscitation at birth
Jaundice in the Healthy Term Newborn
April 2002 Page 14 of 20
Clinical management of hyperbilirubinemia in infants
A bilirubin level that justifies consideration of phototherapy should mandate the investigation of the cause ofhyperbilirubinemia Investigation should include a clinically pertinent history of the mother family historydescription of labour and delivery and infantrsquos clinical course (26) A physical examination should besupplemented by laboratory investigations (Table 1) including determination of unconjugated and conjugatedserum bilirubin concentrations and blood group with direct antibody test (Coombsrsquo test) and hemoglobin andhematocrit levels A complete blood count including differential white cell count and a blood smear for red cellmorphology may be indicated Further tests (eg reticulocyte count G6PD screen) may be indicated based oninitial results ethnicity or clinical presentation Testing for serum electrolytes and albumin or protein areindicated in some situations such as suspected dehydration or when bilirubin levels approach exchange valuesIn the absence of drugs or clinical states that alter the binding of bilirubin by albumin the bilirubin to albuminor the bilirubin to protein ratio reflects the free bilirubin concentration and the binding capacity of the serum(27-29) At a bilirubin concentration close to exchange transfusion levels some clinicians may wish to ensurethat serum bilirubin binding is normal (albumin 25 gL or greater protein 54 gL or greater) Values belowthese levels may be associated with low bilirubin binding and may be used by the clinician when decidingwhether further intervention (eg exchange transfusion) should take place (27)
TABLE 1 Laboratory investigation for hyperbilirubinemia in term newborn infants
Indicated (if bilirubin concentrations reach phototherapy levels) Serum total or unconjugated bilirubin concentration Serum conjugated bilirubin concentration Blood group with direct antibody test (Coombsrsquo test) Hemoglobin and hematocrit determinations
Optional (in specific clinical circumstances) Complete blood count including manual differential white cell count Blood smear for red cell morphology Reticulocyte count Glucose-6-phosphate dehydrogenase screen Serum electrolytes and albumin or protein concentrations
For infants with prolonged jaundice (lasting longer than seven days) or with conjugated hyperbilirubinemia(greater than 30 micromolL) additional investigation and management may be required and a consultation with aspecialist may be needed (30)
During the past decade most nurseries have shortened the time of hospital stay for term healthy newborninfants Early discharge of neonates means that jaundice is not often recognized at discharge (31) The CanadianPaediatric Society reiterates the importance of allowing early discharge only if a healthy status is confirmed foreach baby and appropriate follow-up is provided (32) Appropriate parental education about feeding signs ofdehydration and jaundice must be implemented in hospital nurseries Testing for serum bilirubin concentrationsmust be readily available for newborns on an out-patient basis Readmission to hospital (usually the hospital ofbirth) may be necessary for the investigation and management of hyperbilirubinemia
Exchange transfusion If phototherapy fails to control the rising bilirubin levels exchange transfusion is indicated to lower serumbilirubin concentrations For healthy term infants without risk factors exchange transfusion should beconsidered at serum unconjugated bilirubin concentrations of 400 to 430 micromolL For term infants with riskfactors the level should be 340 micromolL For infants who initially present with serum bilirubin concentrations in
Jaundice in the Healthy Term Newborn
April 2002 Page 15 of 20
excess of exchange levels intensive phototherapy should produce a decline of serum unconjugated bilirubinfrom 20 to 35 micromolL within 4 to 6 h and levels should continue to fall thereafter and remain below thethreshold for exchange transfusion If the bilirubin concentration does not decrease after adequate rehydrationand 4 to 6 h of intensive phototherapy exchange transfusion should be considered Preparation for thisincluding ensuring availability of blood should occur shortly after the admission of babies whose bilirubinconcentrations exceed exchange levels Appropriate consultation should be obtained if the etiology ofhyperbilirubinemia is unclear the infant is ill and particularly if bilirubin concentrations are approachingexchange levels Because the risks of exchange transfusion are significant the best management may bereviewed with an expert opinion from a neonatologist
Conclusions Hyperbilirubinemia in apparently healthy term newborn infants continues to hold the potential threat ofcomplications from bilirubin encephalopathy and kernicterus Careful assessment of risk factors judicious useof phototherapy appropriate laboratory monitoring and specific treatment of other disorders (eg sepsis) areessential for the optimal management of hyperbilirubinemia Appropriate laboratory facilities must be availableto measure bilirubin concentrations for out-patients in required clinical situations Readmission to hospital maybe required if phototherapy is necessary Guidelines for phototherapy are presented for term babies with andwithout identifiable risk factors
References
1 Fetus and Newborn Committee Canadian Paediatric Society Use of phototherapy for neonatalhyperbilirubinemia Can Med Assoc J 19861341237-45 2 American Academy of Pediatrics Practice parameter Management of hyperbilirubinemia in the healthy termnewborn Pediatrics 199494558-65 3 Hansen TWR Therapeutical approaches to neonatal jaundice an international survey Clin Pediatr199635309-16 4 Valaes T Koliopoulos C Koltsidopoulos A The impact of phototherapy in the management of neonatalhyperbilirubinemia comparison of historical cohorts Acta Paediatrica 199685273-6 5 Gustafson PA Boyle DW Bilirubin index a new standard for intervention Med Hypotheses 199545409-16 6 Torres-Torres M Tayaba R Weintraub A Holzman IR New perspectives on neonatal hyperbilirubinemiaMount Sinai J Med 199461424-8 7 Lazar L Litwin A Merlob P Phototherapy for neonatal nonhemolytic hyperbilirubinemia analysis ofrebound and indications for discontinuing therapy Clin Pediatr 199332264-7 8 Newman TB Maisels MJ Evaluation and treatment of jaundice in the term newborn Pediatrics 199289809-18 9 McMillan DD Lockyer JM Magnan L Akierman A Parboosingh JT Effect of educational program andinterview on adoption of guidelines for the management of neonatal hyperbilirubinemia Can Med Assoc J1991144707-12 10 Brown AK Johnson L Loss of concern about jaundice and the reemergence of kernicterus in full-terminfants in the era of managed care In Fanaroff AA Klaus MH eds The Year Book of Neonatal and PerinatalMedicine Philadelphia Mosby Yearbook 199617-28 11 Valaes T Bilirubin toxicity The problem was solved a generation ago Pediatrics 199289819-21 12 Wennberg RP Bilirubin recommendations present problems New guidelines simplistic and untestedPediatrics 199289821-2 13 Merenstein GB lsquoNewrsquo bilirubin recommendations questioned Pediatrics 199289822-3 14 Poland RL In search of a lsquogold standardrsquo for bilirubin toxicity Pediatrics 199289823-4 15 Brown AK Seidman DS Stevenson DK Jaundice in healthy term neonates Do we need new action levelsor new approaches Pediatrics 199289827-9 16 Johnson L Yet another expert opinion on bilirubin toxicity Pediatrics 199289829-31
Jaundice in the Healthy Term Newborn
April 2002 Page 16 of 20
17 MacDonald MG Hidden risks Early discharge and bilirubin toxicity due to glucose-6-phosphatedehydrogenase deficiency Pediatrics 199596734-8 18 Maisels MJ Newman TB Kernicterus in otherwise healthy breast-fed newborns Pediatrics 199596730-3 19 Vogl TP Phototherapy of neonatal hyperbilirubinemia bilirubin in unexposed areas of the skin J Pediatr197485707-1020 Rubaltelli FF Carli M The effect of light on cutaneous bilirubin Biol Neonate 197118457-62 21 Sisson TR Kendall N Shaw E et al Phototherapy of jaundice in the newborn infant 2 Effect of variouslight intensities J Pediatr 19738135-8 22 Bonta BW Warshaw JB Importance of radiant flux in the treatment of hyperbilirubinemia failure ofoverhead phototherapy units in intensive care units Pediatrics 197657502-5 23 Warshaw JB Gagliardi J Patel A A comparison of fluorescent and non-fluorescent light source forphototherapy Pediatrics 198065795-8 24 Ennever JF Blue light green light white light more light treatment of neonatal jaundice Clin Perinatol199017467-8125 Auerbach KG Gartner LM Breastfeeding and human milk their association with jaundice in the neonateClin Perinatol 19871489-108 26 Maisels MJ Jaundice in the newborn Pediatr Rev 19823305-20 27 Ahlfors CE Criteria for exchange transfusion in jaundiced newborns Pediatrics 199493488-94 28 Odell GB Storey GNB Rosenberg LA Studies in kernicterus III The saturation of serum protein withbilirubin during neonatal life and its relationship to brain damage at 5 years J Pediatr 19707612-21 29 Wirth FH Goldberg KE Lubchenco LO The neurologic outcome of infants evaluated for unboundbilirubin Pediatr Res 19759385-91 30 Haber BA Lake AM Cholestatic jaundice in the newborn Clin Perinatol 199017483-506 31 Maisels MJ Newman TB Jaundice in full-term and near-term babies who leave the hospital within 36hours The pediatricianrsquos nemesis Clin Perinatol 199825295-302 32 Fetus and Newborn Committee Canadian Paediatric Society and Society of Obstetricians andGynaecologists of Canada Facilitating discharge home following a normal term birth Paediatr Child Health19961165-8
Fetus and Newborn Committee Members Drs John Watts Department of Paediatrics Childrenrsquos Hospital ndash Hamilton Health Sciences CentreHamilton Ontario (director responsible) Douglas McMillan Department of Pediatrics Foothills HospitalCalgary Alberta (chair) Arne Ohlsson Department of Paediatrics Mount Sinai Hospital Toronto Ontario(co-chair) Deborah Davis Childrenrsquos Hospital of Eastern Ontario Ottawa Ontario Daniel Faucher RoyalVictoria Hospital Montreal Quebec (principal author) John Van Aerde Stollery Childrenrsquos Health CentreEdmonton Alberta Michael Vincer IWK-Grace Health Centre Halifax Nova ScotiaConsultant Dr Michael C Klein University of British Columbia Vancouver British Columbia (College ofFamily Physicians of Canada)Liaisons Drs James Lemon Riley Childrenrsquos Hospital Indiana University Medical Center IndianapolisIndiana (American Academy of Pediatrics) Saroj Saigal Department of Paediatrics McMaster UniversityMedical Centre Childrenrsquos Hospital ndash Hamilton Health Sciences Centre Hamilton Ontario (CPS Neonatal-Perinatal Medicine Section) Cheryl Levitt Department of Family Medicine Childrenrsquos Hospital ndash HamiltonHealth Sciences Centre Hamilton Ontario (College of Family Physicians of Canada) Catherine McCourtDirector Bureau of Reproductive amp Child Health Laboratory Centre for Disease Control Ottawa Ontario(Health Canada) Mrs Debbie Fraser-Askin Winnipeg Manitoba (Neonatal Nurses) Dr Line LeducDepartment of Obstetrics-Gynecology Hocircpital Sainte-Justine Montreal Quebec (Society of Obstetricians andGynaecologists of Canada)
Disclaimer The recommendations in this position statement do not indicate an exclusive course oftreatment or procedure to be followed Variations taking into account individual circumstances may beappropriate
Jaundice in the Healthy Term Newborn
April 2002 Page 17 of 20
APPENDIX 3Hyperbilirubinemia Risk Designation for Term and Near-Term Well Newborns
Jaundice in the Healthy Term Newborn
April 2002 Page 18 of 20
APPENDIX 4
American Academy of Pediatrics 1994 Practice parameter Management ofHyperbilirubinemia in the Healthy Term Newborn Pediatrics 94(4) 558-565
(Chart and Algorithm)
Jaundice in the Healthy Term Newborn
April 2002 Page 19 of 20
AlgorithmPediatric clinician evaluatesterm newborn with jaundice
Does the infant have signs of underlyingserious illness (lethargy apnea tachypneatemperature instability behavior changeshepatosplenomegaly persistant vomiting
or persistent feeding difficulty)
1
2
Exit this algorithm to individualizedclinical evaluation including
assessment of jaundice and underlyingdisease
Yes
3
No
Is the infant lt 37 weeks gestational age
4 Exit this algorithm to individualizedclinical evaluation including
assessment of jaundice in light ofprematurity
5
Yes
Is the mothersABO and Rh
blood typing andisoimmune
antibody screenstatus known
Is the mothersblood Rhpositive
Does themothers blood
have anyimmune
antibodies
Consider holding the infantscord blood in the blood bank incase future testing is necessary
6 7 8 9No
Yes Yes No
(Go to Box 10) (Go to Box 10) (Go to Box 10) (Go to Box 13)
No No Yes
Perform blood typing (ABO and Rh) and direct Coombs testingon the infants cord (preferably) or venous blood
10
Is the infantsblood direct
Coombs testpositive
Exit this algorithm to individualized clinical evaluationincluding assessment of jaundice and isoimmune
hemolytic disease
11 12
Yes
Are any of the following risk factors present tosuggest that nonisoimmune hemolytic disease
is possible in this infant(1) Family history of hemolytic anemia
OR(2) Family history of early or severe jaundice
OR(3) Ethnicity or geographic originassociated with hemolytic anemia
OR(4) Early or severe jaundice
Perform appropriate laboratoryassessment of infant including
(but not limited to consideration of)(1) Complete blood count differentialsmear reticulocyte count(2) G6PD screen(3) Hemoglobin electrophoresis
1314
No
No
No
(Go to Box 16)
Does the evaluation suggesthemolytic disease
15
Yes
(Go to Box 17)(Go to Box 16)
No
Jaundice in the Healthy Term Newborn
April 2002 Page 20 of 20
AlgorithmIs the infant
jaundiced andlt 24 hours of
age
Exit this algorithm to individualizedclinical evaluation includingassessment of jaundice and
nonisoimmune hemolytic disease
Is jaundiceclinicallysignificant by medical
judgment
(1) Measure infantstotal serum bilirubin(2) Go to Box 27
Healthy term infant with jaundice not clinicallysignificant by medical judgment
Follow infant in routine clinical supervision
1617
18 19
20
21
(Go to Box 22)
Yes
Yes
No
No
Is jaundicepersisting
gt 2 weeks
Does this infant haveabnormal physicalexam results dark
urine or light stools
Is jaundice persistinggt 3 weeks
Perform appropriate physical andlaboratory assessment of theinfant including possibility of
cholestatic jaundice
Provide routine carerecommend routine
feeding and follow-up Table 2 Management of Hyperbilirubinemia in the Healthy Term NewbornAgehours TSB Level mgdL (umolL)
Consider Phototherapy Exchange ExchangePhototherapy Transfusion Transfusion
if Intensive and IntensivePhototherapy PhototherapyFails
lt24 25-48 gt 12 (170) gt15 (260) gt 20 (340) gt 25 (430)49-72 gt 15 (260) gt 18 (310) gt 25 (430) gt 30 (510)gt 72 gt 17 (290) gt 20 (340) gt 25 (430) gt 30 (510)
TSB indicates total serum bilirubinPhototherapy at these TSB levels is a clinical option meaning that the intervention is availableand may be used on the basis of individual clinical judgement For a more detailed descriptionof phototherapy see the AppendixIntensive phototherapy (Appendix) should produce a decline of TSB of 1 to 2 mgdL within 4 to 6hours and the TSB level should continue to fall and remain below the threshold level for exchangetransfusion If this does not occur it is considered a failure of phototherapyTerm infants who are clinically jaundiced at lt 24 hours old are not considered healthy andrequire further evaluation (see text)
22 23
24
25
26
YesYes
No
YesNo
No 27
Algorithm Management of hyperbilirubinemia inthe healthy term infant
(From Box 19)
Jaundice in the Healthy Term Newborn
April 2002 Page 8 of 20
8 Blackburn S (1995) Hyperbilirubinemia and neonatal jaundice Neonatal Network 14 (7)15-24
9 Canadian Paediatric Society amp the Society of Obstetricians and Gynaecologists of Canada (1996)Joint Policy Statement Facilitating discharge home following a normal term birth Paediatric amp ChildHealth1(2) 165-168Access from httpwwwcpscaenglishstatementsFNfn96-02htm
10 Bhutani V Gourley G Adler S Kreamer B Dalin C Johnson L (2000) NoninvasiveMeasurement of Total Bilirubin in a Multiracial Predischarge Newborn Population to Assess the Riskof Severe Hyperbilirubinemia Pediatrics (106) NO 2 Part 1 of 3
11 Schwoebel A amp Sakraida (1997) Hyperbilirubinemia New approaches to an old problemJournal of Perinatal and Neonatal Nursing 11(3) 78-97
12 Bhutani V Johnson L amp Sivieri E (1999) Predictive ability of a predischarge hour-specificserum bilirubin for subsequent significant hyperbilirubinemia in healthy term and near-term newbornsPediatrics 103(1) 6-14
13 Seidman D Ergaz Z Paz I Laor A Revel-Vilk S Stevenson D amp Gale R (1999)Predicting the risk of jaundice in fullterm healthy newborns A prospective population-based studyJournal of Perinatology 19(8) 564-567
14 Alpay F Sarici U Tosuncuk D Serdar M Inanc N amp Gokcay E (2000) The value offirst-day bilirubin measurement in predicting the development of significant hyperbilirubinemia inhealth term newborns Pediatrics 106(2)
15 Kramer L 1969 Advancement of dermal icterus in the jaundiced newborn American Journal ofDiseases in Children 118 454-458
16 Royal Prince Alfred Hospital 1998 The department of neonatal medicine protocol bookjaundice Sydney Author Accessed May 2001 fromwwwcsnswgovaurpaneonatalhtmlnewprotjaund2htm
17 American Academy of Pediatrics (1994) Practice parameter Management ofhyperbilirubinemia in the healthy term newborn Pediatrics 94(4) 558-565) httpwwwaaporgpolicyhyperbhtm
18 International Lactation Consultant Association (1999) Evidence-Based Guidelines forBreastfeeding Management During the First Fourteen Days Raleigh NC Author
19 Mohrbacher N amp Stock J (1997) The Breastfeeding Answer Book Illinois La Leche League
20 Mills J amp Tudehope D (2001) The Cochrane Database of Systemic Reviews Fibreopticphototherapy for neonatal jaundice Volume (Issue 1)
21 Ludwig M (1990) Phototherapy in the home setting Journal of Pediatric Health Care 4(6)304-308
Jaundice in the Healthy Term Newborn
April 2002 Page 9 of 20
22 Hamelin K amp Seshia M (1998) Home phototherapy for uncomplicated neonatal jaundiceCanadian Nurse Jan 39-40
23 Murphy B amp Welch R (1992) Home phototherapy for the jaundiced full-term newbornJournal of Home Health Care Practitioner 5(1) 26-33
24 British Columbia Reproductive Care Program (2001) British Columbia Newborn Care PathOutcomes Teaching amp Interventions Vancouver Author
25 Campbell River Hospital (2000) Protocol Hyperbilirubinemia ndash Home PhototherapyManagement Campbell River BC Author
26 Mississauga Hospital (1994) Protocol Home Phototherapy Programme Mississauga ONAuthor
27 University of Manitoba Health Science Centre () Protocol Home Phototherapy ProgramWinnepeg Author Access from httpwwwumanitobacawomens_healthhschomethtm
WEB RESOURCES
httpwwwaaporgpolicyhyperbhtm
wwwcpscaenglishstatementsFNfn98-02htm
httpwwwcpscaenglishstatementsFNfn96-02htm
wwwcsnswgovaurpaneonatalhtmlnewprotjaund2htm
httpwwwumanitobacawomens_healthhschomethtm
Jaundice in the Healthy Term Newborn
April 2002 Page 10 of 20
Management of Newborn Jaundice at Home Program
Referral for the Healthy Term Infant
PHN Identifies jaundice in the newborn
1 Preterm Infant RhABO incompatibility2 Look or act ill (eg lethargic apnea tachycardia
temperature unstable poor feeding changed behaviorpersistant vomiting insufficient voidingstooling)
No
Family hx of early or severejaundice Ethnicity relevant(Mediterranean SE Asian)
No
Infant less than24 hrs
No
Is jaundiceclinically
significant
No
Jaundice persistedgt 2 weeks
Jaundice gt3weeks
Routinecare and
feedsNo
Routinecare and
feedsNo
RoutineClinical
Supervis-ion
No
Refer to MD ASAPYes
Refer to MD forinvestigationeg
G6PD SpherocytosisYes
Refer to MD fornon - isoimmune
hemolyticdisease
investigation
Yes
Refer to MD forfollow-up with total
serum bilirubinYes
Any abnormal physicalfindings Dark urine
light stoolsRefer to MDYes Yes
Refer to MDYes
APPENDIX 1 (Example)
Developed by the Coordinated Maternity Standards Committee South FraserHealth Region and Dr K Danso Pediatrician Surrey Memorial Hospital
Revised 1997 Copied with permission
Jaundice in the Healthy Term Newborn
April 2002 Page 11 of 20
APPENDIX 2
Approach to the Management of Hyperbilirubinemiain Term Newborn Infants
A Joint Statement with the College of Family Physicians of CanadaPaediatrics amp Child Health 19994(2)161-164Reference No FN98-02Reaffirmed February 2001
Reprints of this position statement are available from the Canadian Paediatric Society100-2204 Walkley Road Ottawa ON K1G 4G8 phone (613) 526-9397 fax (613) 526-3332
Contents bull Background bull Phototherapy bull Clinical management of hyperbilirubinemia in infants bull Exchange transfusion bull Conclusions bull References
Conflicting reports have led to confusion about the optimal management of jaundice in otherwise healthy terminfants (1-9) The lsquokinder gentler approachrsquo to neonatal hyperbilirubinemia proposed in 1992 by Newman andMaisels (8) resulted in a 1994 statement by the American Academy of Pediatrics (2) that addressed themanagement of healthy term infant without risk factors Recently there has been an increase in the number ofterm infants reported with kernicterus (10) It is important to note that while some of the infants reported withkernicterus had features that would place them in a high risk category some presented with severe jaundiceonly and no identifiable risk factors (10) The infants reported were commonly breastfed and frequentlydischarged from hospital very soon after birth (10) Nonetheless the current standards (2) for the managementof hyperbilirubinemia in the healthy term infant have become controversial This document updates information previously published by the Canadian Paediatric Society (1) It provides anoverview of the proposed management of hyperbilirubinemia based on available evidence even thoughrandomized controlled trials are not available to allow a conclusive assessment of the risk associated withhyperbilirubinemia in the clinical situations encountered in practice The objective of this overview is toestablish a management plan that will minimize the risk of kernicterus in term infants both with and withoutrisk factors Although scientific evidence has not established a clear link between specific bilirubinconcentrations and the development of kernicterus in healthy term babies information to date has beenincorporated into the following guidelines Background
Kernicterus is a neurological condition characterized by deep yellow staining of the basal nuclei Theaccompanying clinical syndrome results from the destructive changes of these neuronal populations Initiallythe signs are lethargy hypotonia and seizures later the infants may develop athetoid cerebral palsy mentalretardation and deafness When neurological signs evident in the infant permanent damage has alreadyoccurred leading to death or long term disability Therefore management strategies are aimed at preventingkernicterus
Jaundice in the Healthy Term Newborn
April 2002 Page 12 of 20
Until recently these strategies suggested maintaining serum unconjugated bilirubin concentrations below 340micromolL (20 mgdL) in healthy term infants through the use of phototherapy or exchange transfusion (11) Whileexchange transfusions had been a frequent occurrence from the 1950s to the 1970s and may sometimes still berequired phototherapy has become the mainstay of medical management of hyperbilirubinemia since that time
The cases of kernicterus originally described occurred mainly in infants with hemolytic disease Higher serumunconjugated bilirubin concentrations may be safe in healthy term infants without hemolytic disease It is notpossible to predict at what level an individual infant may develop kernicterus
Several authors have expressed serious concerns over the approach of allowing higher serum unconjugatedbilirubin concentrations to occur before investigating and treating these term infants (11-16) Brown andJohnson (10) have reported 23 cases of kernicterus occurring since 1989 16 in term and seven in near terminfants In these infants peak unconjugated bilirubin concentrations of 375 to 860 micromolL (22 to 50 mgdL)were seen All but one infant was breastfed Other associations found in these infants with kernicterus weredehydration (seven infants) glucose-6-phosphate dehydrogenase (G6PD) deficiency (five infants) ABOalloimmunization (one infant) hemolysis of unknown cause (five infants) familial etiology (one infant) andotherwise unexplained early jaundice clinically evident before 24 h of age (six infants) Similar cases have beenreported by others (1718) Although many of these babies were subsequently found to have additional riskfactors these factors were not often identified at the time the baby was noted to be jaundiced
Since the introduction in the 1990s of the kinder gentler approach to the management of hyperbilirubinemia agreat deal of confusion has arisen about approaches to the management of hyperbilirubinemia in healthy terminfants This confusion has extended to the care of borderline preterm infants who have often been treated asterm infants A recently published international survey reported considerable variability in the approach tohyperbilirubinemia and the use of phototherapy among neonatal units worldwide (3)
PhototherapyThe goal of hyperbilirubinemia treatment is to avoid bilirubin concentrations that may result in kernicterusPhototherapy remains an effective therapeutic intervention that decreases bilirubin concentrations therebypreventing elevated bilirubin levels associated with permanent sequelae
The effectiveness of phototherapy is related to the area of skin exposed and the radiant energy and thewavelength of the light (19-23) Phototherapy acts on unconjugated bilirubin to a depth of 2 mm from theepidermis Phototherapy changes the bilirubin through structural photoisomerization into water-solublelumirubin that is excreted in the urine (19) The fall in bilirubin level is proportionately greater in the skin thanin the serum (20) Therefore the infant receiving phototherapy should have as much skin as possible exposed tothe lights More intense phototherapy may be achieved by using multiple sources of phototherapy double ortriple phototherapy is recommended to optimize the skin surface exposed and therefore the efficacy ofphototherapy More detailed discussion of the physics of phototherapy has been published (124) It is important to recognize the relationship between dehydration and hyperbilirubinemia Dehydration may beassociated with increased serum bilirubin concentrations and may be exacerbated by phototherapy Alljaundiced infants should be adequately hydrated before and during phototherapy Breastfeeding is notcontraindicated in the presence of hyperbilirubinemia and should be continued More frequent breastfeedingsmay be beneficial (25)
The concentrations of bilirubin at which phototherapy might be initiated in healthy term infants and those withrisk factors are shown in Figure 1 Guidelines for phototherapy in low birth weight infants remain as previouslypublished (1) The bilirubin concentrations at which phototherapy is suggested by the Canadian PaediatricSociety in the present statement are more conservative than the current recommendations of the AmericanAcademy of Pediatrics (2) If the infant is a healthy term newborn phototherapy should be started as indicated
Jaundice in the Healthy Term Newborn
April 2002 Page 13 of 20
in the upper curve of Figure 1 If the infant has one or more risk factors a clinical decision should be made toinitiate phototherapy at the concentration indicated by the lower curve
Figure 1 Guidelines for initiation of phototherapy for hyperbilirubinemia in term infants with and without riskfactors Some risk factors include gestional age younger than 37 weeks birth weight less than 2500 ghemolysis jaundice at younger than 24 h of age sepsis and the need for resuscitation at birth
The timely recognition of risk factors is essential to minimize the danger of kernicterus The risk factors are asfollows
bull gestational age younger than 37 weeks and birth weight less than 2500 g bull hemolysis due to maternal isoimmunization G6PD deficiency spherocytosis or other causes bull jaundice at less than 24 h of age bull sepsis and bull the need for resuscitation at birth
Jaundice in the Healthy Term Newborn
April 2002 Page 14 of 20
Clinical management of hyperbilirubinemia in infants
A bilirubin level that justifies consideration of phototherapy should mandate the investigation of the cause ofhyperbilirubinemia Investigation should include a clinically pertinent history of the mother family historydescription of labour and delivery and infantrsquos clinical course (26) A physical examination should besupplemented by laboratory investigations (Table 1) including determination of unconjugated and conjugatedserum bilirubin concentrations and blood group with direct antibody test (Coombsrsquo test) and hemoglobin andhematocrit levels A complete blood count including differential white cell count and a blood smear for red cellmorphology may be indicated Further tests (eg reticulocyte count G6PD screen) may be indicated based oninitial results ethnicity or clinical presentation Testing for serum electrolytes and albumin or protein areindicated in some situations such as suspected dehydration or when bilirubin levels approach exchange valuesIn the absence of drugs or clinical states that alter the binding of bilirubin by albumin the bilirubin to albuminor the bilirubin to protein ratio reflects the free bilirubin concentration and the binding capacity of the serum(27-29) At a bilirubin concentration close to exchange transfusion levels some clinicians may wish to ensurethat serum bilirubin binding is normal (albumin 25 gL or greater protein 54 gL or greater) Values belowthese levels may be associated with low bilirubin binding and may be used by the clinician when decidingwhether further intervention (eg exchange transfusion) should take place (27)
TABLE 1 Laboratory investigation for hyperbilirubinemia in term newborn infants
Indicated (if bilirubin concentrations reach phototherapy levels) Serum total or unconjugated bilirubin concentration Serum conjugated bilirubin concentration Blood group with direct antibody test (Coombsrsquo test) Hemoglobin and hematocrit determinations
Optional (in specific clinical circumstances) Complete blood count including manual differential white cell count Blood smear for red cell morphology Reticulocyte count Glucose-6-phosphate dehydrogenase screen Serum electrolytes and albumin or protein concentrations
For infants with prolonged jaundice (lasting longer than seven days) or with conjugated hyperbilirubinemia(greater than 30 micromolL) additional investigation and management may be required and a consultation with aspecialist may be needed (30)
During the past decade most nurseries have shortened the time of hospital stay for term healthy newborninfants Early discharge of neonates means that jaundice is not often recognized at discharge (31) The CanadianPaediatric Society reiterates the importance of allowing early discharge only if a healthy status is confirmed foreach baby and appropriate follow-up is provided (32) Appropriate parental education about feeding signs ofdehydration and jaundice must be implemented in hospital nurseries Testing for serum bilirubin concentrationsmust be readily available for newborns on an out-patient basis Readmission to hospital (usually the hospital ofbirth) may be necessary for the investigation and management of hyperbilirubinemia
Exchange transfusion If phototherapy fails to control the rising bilirubin levels exchange transfusion is indicated to lower serumbilirubin concentrations For healthy term infants without risk factors exchange transfusion should beconsidered at serum unconjugated bilirubin concentrations of 400 to 430 micromolL For term infants with riskfactors the level should be 340 micromolL For infants who initially present with serum bilirubin concentrations in
Jaundice in the Healthy Term Newborn
April 2002 Page 15 of 20
excess of exchange levels intensive phototherapy should produce a decline of serum unconjugated bilirubinfrom 20 to 35 micromolL within 4 to 6 h and levels should continue to fall thereafter and remain below thethreshold for exchange transfusion If the bilirubin concentration does not decrease after adequate rehydrationand 4 to 6 h of intensive phototherapy exchange transfusion should be considered Preparation for thisincluding ensuring availability of blood should occur shortly after the admission of babies whose bilirubinconcentrations exceed exchange levels Appropriate consultation should be obtained if the etiology ofhyperbilirubinemia is unclear the infant is ill and particularly if bilirubin concentrations are approachingexchange levels Because the risks of exchange transfusion are significant the best management may bereviewed with an expert opinion from a neonatologist
Conclusions Hyperbilirubinemia in apparently healthy term newborn infants continues to hold the potential threat ofcomplications from bilirubin encephalopathy and kernicterus Careful assessment of risk factors judicious useof phototherapy appropriate laboratory monitoring and specific treatment of other disorders (eg sepsis) areessential for the optimal management of hyperbilirubinemia Appropriate laboratory facilities must be availableto measure bilirubin concentrations for out-patients in required clinical situations Readmission to hospital maybe required if phototherapy is necessary Guidelines for phototherapy are presented for term babies with andwithout identifiable risk factors
References
1 Fetus and Newborn Committee Canadian Paediatric Society Use of phototherapy for neonatalhyperbilirubinemia Can Med Assoc J 19861341237-45 2 American Academy of Pediatrics Practice parameter Management of hyperbilirubinemia in the healthy termnewborn Pediatrics 199494558-65 3 Hansen TWR Therapeutical approaches to neonatal jaundice an international survey Clin Pediatr199635309-16 4 Valaes T Koliopoulos C Koltsidopoulos A The impact of phototherapy in the management of neonatalhyperbilirubinemia comparison of historical cohorts Acta Paediatrica 199685273-6 5 Gustafson PA Boyle DW Bilirubin index a new standard for intervention Med Hypotheses 199545409-16 6 Torres-Torres M Tayaba R Weintraub A Holzman IR New perspectives on neonatal hyperbilirubinemiaMount Sinai J Med 199461424-8 7 Lazar L Litwin A Merlob P Phototherapy for neonatal nonhemolytic hyperbilirubinemia analysis ofrebound and indications for discontinuing therapy Clin Pediatr 199332264-7 8 Newman TB Maisels MJ Evaluation and treatment of jaundice in the term newborn Pediatrics 199289809-18 9 McMillan DD Lockyer JM Magnan L Akierman A Parboosingh JT Effect of educational program andinterview on adoption of guidelines for the management of neonatal hyperbilirubinemia Can Med Assoc J1991144707-12 10 Brown AK Johnson L Loss of concern about jaundice and the reemergence of kernicterus in full-terminfants in the era of managed care In Fanaroff AA Klaus MH eds The Year Book of Neonatal and PerinatalMedicine Philadelphia Mosby Yearbook 199617-28 11 Valaes T Bilirubin toxicity The problem was solved a generation ago Pediatrics 199289819-21 12 Wennberg RP Bilirubin recommendations present problems New guidelines simplistic and untestedPediatrics 199289821-2 13 Merenstein GB lsquoNewrsquo bilirubin recommendations questioned Pediatrics 199289822-3 14 Poland RL In search of a lsquogold standardrsquo for bilirubin toxicity Pediatrics 199289823-4 15 Brown AK Seidman DS Stevenson DK Jaundice in healthy term neonates Do we need new action levelsor new approaches Pediatrics 199289827-9 16 Johnson L Yet another expert opinion on bilirubin toxicity Pediatrics 199289829-31
Jaundice in the Healthy Term Newborn
April 2002 Page 16 of 20
17 MacDonald MG Hidden risks Early discharge and bilirubin toxicity due to glucose-6-phosphatedehydrogenase deficiency Pediatrics 199596734-8 18 Maisels MJ Newman TB Kernicterus in otherwise healthy breast-fed newborns Pediatrics 199596730-3 19 Vogl TP Phototherapy of neonatal hyperbilirubinemia bilirubin in unexposed areas of the skin J Pediatr197485707-1020 Rubaltelli FF Carli M The effect of light on cutaneous bilirubin Biol Neonate 197118457-62 21 Sisson TR Kendall N Shaw E et al Phototherapy of jaundice in the newborn infant 2 Effect of variouslight intensities J Pediatr 19738135-8 22 Bonta BW Warshaw JB Importance of radiant flux in the treatment of hyperbilirubinemia failure ofoverhead phototherapy units in intensive care units Pediatrics 197657502-5 23 Warshaw JB Gagliardi J Patel A A comparison of fluorescent and non-fluorescent light source forphototherapy Pediatrics 198065795-8 24 Ennever JF Blue light green light white light more light treatment of neonatal jaundice Clin Perinatol199017467-8125 Auerbach KG Gartner LM Breastfeeding and human milk their association with jaundice in the neonateClin Perinatol 19871489-108 26 Maisels MJ Jaundice in the newborn Pediatr Rev 19823305-20 27 Ahlfors CE Criteria for exchange transfusion in jaundiced newborns Pediatrics 199493488-94 28 Odell GB Storey GNB Rosenberg LA Studies in kernicterus III The saturation of serum protein withbilirubin during neonatal life and its relationship to brain damage at 5 years J Pediatr 19707612-21 29 Wirth FH Goldberg KE Lubchenco LO The neurologic outcome of infants evaluated for unboundbilirubin Pediatr Res 19759385-91 30 Haber BA Lake AM Cholestatic jaundice in the newborn Clin Perinatol 199017483-506 31 Maisels MJ Newman TB Jaundice in full-term and near-term babies who leave the hospital within 36hours The pediatricianrsquos nemesis Clin Perinatol 199825295-302 32 Fetus and Newborn Committee Canadian Paediatric Society and Society of Obstetricians andGynaecologists of Canada Facilitating discharge home following a normal term birth Paediatr Child Health19961165-8
Fetus and Newborn Committee Members Drs John Watts Department of Paediatrics Childrenrsquos Hospital ndash Hamilton Health Sciences CentreHamilton Ontario (director responsible) Douglas McMillan Department of Pediatrics Foothills HospitalCalgary Alberta (chair) Arne Ohlsson Department of Paediatrics Mount Sinai Hospital Toronto Ontario(co-chair) Deborah Davis Childrenrsquos Hospital of Eastern Ontario Ottawa Ontario Daniel Faucher RoyalVictoria Hospital Montreal Quebec (principal author) John Van Aerde Stollery Childrenrsquos Health CentreEdmonton Alberta Michael Vincer IWK-Grace Health Centre Halifax Nova ScotiaConsultant Dr Michael C Klein University of British Columbia Vancouver British Columbia (College ofFamily Physicians of Canada)Liaisons Drs James Lemon Riley Childrenrsquos Hospital Indiana University Medical Center IndianapolisIndiana (American Academy of Pediatrics) Saroj Saigal Department of Paediatrics McMaster UniversityMedical Centre Childrenrsquos Hospital ndash Hamilton Health Sciences Centre Hamilton Ontario (CPS Neonatal-Perinatal Medicine Section) Cheryl Levitt Department of Family Medicine Childrenrsquos Hospital ndash HamiltonHealth Sciences Centre Hamilton Ontario (College of Family Physicians of Canada) Catherine McCourtDirector Bureau of Reproductive amp Child Health Laboratory Centre for Disease Control Ottawa Ontario(Health Canada) Mrs Debbie Fraser-Askin Winnipeg Manitoba (Neonatal Nurses) Dr Line LeducDepartment of Obstetrics-Gynecology Hocircpital Sainte-Justine Montreal Quebec (Society of Obstetricians andGynaecologists of Canada)
Disclaimer The recommendations in this position statement do not indicate an exclusive course oftreatment or procedure to be followed Variations taking into account individual circumstances may beappropriate
Jaundice in the Healthy Term Newborn
April 2002 Page 17 of 20
APPENDIX 3Hyperbilirubinemia Risk Designation for Term and Near-Term Well Newborns
Jaundice in the Healthy Term Newborn
April 2002 Page 18 of 20
APPENDIX 4
American Academy of Pediatrics 1994 Practice parameter Management ofHyperbilirubinemia in the Healthy Term Newborn Pediatrics 94(4) 558-565
(Chart and Algorithm)
Jaundice in the Healthy Term Newborn
April 2002 Page 19 of 20
AlgorithmPediatric clinician evaluatesterm newborn with jaundice
Does the infant have signs of underlyingserious illness (lethargy apnea tachypneatemperature instability behavior changeshepatosplenomegaly persistant vomiting
or persistent feeding difficulty)
1
2
Exit this algorithm to individualizedclinical evaluation including
assessment of jaundice and underlyingdisease
Yes
3
No
Is the infant lt 37 weeks gestational age
4 Exit this algorithm to individualizedclinical evaluation including
assessment of jaundice in light ofprematurity
5
Yes
Is the mothersABO and Rh
blood typing andisoimmune
antibody screenstatus known
Is the mothersblood Rhpositive
Does themothers blood
have anyimmune
antibodies
Consider holding the infantscord blood in the blood bank incase future testing is necessary
6 7 8 9No
Yes Yes No
(Go to Box 10) (Go to Box 10) (Go to Box 10) (Go to Box 13)
No No Yes
Perform blood typing (ABO and Rh) and direct Coombs testingon the infants cord (preferably) or venous blood
10
Is the infantsblood direct
Coombs testpositive
Exit this algorithm to individualized clinical evaluationincluding assessment of jaundice and isoimmune
hemolytic disease
11 12
Yes
Are any of the following risk factors present tosuggest that nonisoimmune hemolytic disease
is possible in this infant(1) Family history of hemolytic anemia
OR(2) Family history of early or severe jaundice
OR(3) Ethnicity or geographic originassociated with hemolytic anemia
OR(4) Early or severe jaundice
Perform appropriate laboratoryassessment of infant including
(but not limited to consideration of)(1) Complete blood count differentialsmear reticulocyte count(2) G6PD screen(3) Hemoglobin electrophoresis
1314
No
No
No
(Go to Box 16)
Does the evaluation suggesthemolytic disease
15
Yes
(Go to Box 17)(Go to Box 16)
No
Jaundice in the Healthy Term Newborn
April 2002 Page 20 of 20
AlgorithmIs the infant
jaundiced andlt 24 hours of
age
Exit this algorithm to individualizedclinical evaluation includingassessment of jaundice and
nonisoimmune hemolytic disease
Is jaundiceclinicallysignificant by medical
judgment
(1) Measure infantstotal serum bilirubin(2) Go to Box 27
Healthy term infant with jaundice not clinicallysignificant by medical judgment
Follow infant in routine clinical supervision
1617
18 19
20
21
(Go to Box 22)
Yes
Yes
No
No
Is jaundicepersisting
gt 2 weeks
Does this infant haveabnormal physicalexam results dark
urine or light stools
Is jaundice persistinggt 3 weeks
Perform appropriate physical andlaboratory assessment of theinfant including possibility of
cholestatic jaundice
Provide routine carerecommend routine
feeding and follow-up Table 2 Management of Hyperbilirubinemia in the Healthy Term NewbornAgehours TSB Level mgdL (umolL)
Consider Phototherapy Exchange ExchangePhototherapy Transfusion Transfusion
if Intensive and IntensivePhototherapy PhototherapyFails
lt24 25-48 gt 12 (170) gt15 (260) gt 20 (340) gt 25 (430)49-72 gt 15 (260) gt 18 (310) gt 25 (430) gt 30 (510)gt 72 gt 17 (290) gt 20 (340) gt 25 (430) gt 30 (510)
TSB indicates total serum bilirubinPhototherapy at these TSB levels is a clinical option meaning that the intervention is availableand may be used on the basis of individual clinical judgement For a more detailed descriptionof phototherapy see the AppendixIntensive phototherapy (Appendix) should produce a decline of TSB of 1 to 2 mgdL within 4 to 6hours and the TSB level should continue to fall and remain below the threshold level for exchangetransfusion If this does not occur it is considered a failure of phototherapyTerm infants who are clinically jaundiced at lt 24 hours old are not considered healthy andrequire further evaluation (see text)
22 23
24
25
26
YesYes
No
YesNo
No 27
Algorithm Management of hyperbilirubinemia inthe healthy term infant
(From Box 19)
Jaundice in the Healthy Term Newborn
April 2002 Page 9 of 20
22 Hamelin K amp Seshia M (1998) Home phototherapy for uncomplicated neonatal jaundiceCanadian Nurse Jan 39-40
23 Murphy B amp Welch R (1992) Home phototherapy for the jaundiced full-term newbornJournal of Home Health Care Practitioner 5(1) 26-33
24 British Columbia Reproductive Care Program (2001) British Columbia Newborn Care PathOutcomes Teaching amp Interventions Vancouver Author
25 Campbell River Hospital (2000) Protocol Hyperbilirubinemia ndash Home PhototherapyManagement Campbell River BC Author
26 Mississauga Hospital (1994) Protocol Home Phototherapy Programme Mississauga ONAuthor
27 University of Manitoba Health Science Centre () Protocol Home Phototherapy ProgramWinnepeg Author Access from httpwwwumanitobacawomens_healthhschomethtm
WEB RESOURCES
httpwwwaaporgpolicyhyperbhtm
wwwcpscaenglishstatementsFNfn98-02htm
httpwwwcpscaenglishstatementsFNfn96-02htm
wwwcsnswgovaurpaneonatalhtmlnewprotjaund2htm
httpwwwumanitobacawomens_healthhschomethtm
Jaundice in the Healthy Term Newborn
April 2002 Page 10 of 20
Management of Newborn Jaundice at Home Program
Referral for the Healthy Term Infant
PHN Identifies jaundice in the newborn
1 Preterm Infant RhABO incompatibility2 Look or act ill (eg lethargic apnea tachycardia
temperature unstable poor feeding changed behaviorpersistant vomiting insufficient voidingstooling)
No
Family hx of early or severejaundice Ethnicity relevant(Mediterranean SE Asian)
No
Infant less than24 hrs
No
Is jaundiceclinically
significant
No
Jaundice persistedgt 2 weeks
Jaundice gt3weeks
Routinecare and
feedsNo
Routinecare and
feedsNo
RoutineClinical
Supervis-ion
No
Refer to MD ASAPYes
Refer to MD forinvestigationeg
G6PD SpherocytosisYes
Refer to MD fornon - isoimmune
hemolyticdisease
investigation
Yes
Refer to MD forfollow-up with total
serum bilirubinYes
Any abnormal physicalfindings Dark urine
light stoolsRefer to MDYes Yes
Refer to MDYes
APPENDIX 1 (Example)
Developed by the Coordinated Maternity Standards Committee South FraserHealth Region and Dr K Danso Pediatrician Surrey Memorial Hospital
Revised 1997 Copied with permission
Jaundice in the Healthy Term Newborn
April 2002 Page 11 of 20
APPENDIX 2
Approach to the Management of Hyperbilirubinemiain Term Newborn Infants
A Joint Statement with the College of Family Physicians of CanadaPaediatrics amp Child Health 19994(2)161-164Reference No FN98-02Reaffirmed February 2001
Reprints of this position statement are available from the Canadian Paediatric Society100-2204 Walkley Road Ottawa ON K1G 4G8 phone (613) 526-9397 fax (613) 526-3332
Contents bull Background bull Phototherapy bull Clinical management of hyperbilirubinemia in infants bull Exchange transfusion bull Conclusions bull References
Conflicting reports have led to confusion about the optimal management of jaundice in otherwise healthy terminfants (1-9) The lsquokinder gentler approachrsquo to neonatal hyperbilirubinemia proposed in 1992 by Newman andMaisels (8) resulted in a 1994 statement by the American Academy of Pediatrics (2) that addressed themanagement of healthy term infant without risk factors Recently there has been an increase in the number ofterm infants reported with kernicterus (10) It is important to note that while some of the infants reported withkernicterus had features that would place them in a high risk category some presented with severe jaundiceonly and no identifiable risk factors (10) The infants reported were commonly breastfed and frequentlydischarged from hospital very soon after birth (10) Nonetheless the current standards (2) for the managementof hyperbilirubinemia in the healthy term infant have become controversial This document updates information previously published by the Canadian Paediatric Society (1) It provides anoverview of the proposed management of hyperbilirubinemia based on available evidence even thoughrandomized controlled trials are not available to allow a conclusive assessment of the risk associated withhyperbilirubinemia in the clinical situations encountered in practice The objective of this overview is toestablish a management plan that will minimize the risk of kernicterus in term infants both with and withoutrisk factors Although scientific evidence has not established a clear link between specific bilirubinconcentrations and the development of kernicterus in healthy term babies information to date has beenincorporated into the following guidelines Background
Kernicterus is a neurological condition characterized by deep yellow staining of the basal nuclei Theaccompanying clinical syndrome results from the destructive changes of these neuronal populations Initiallythe signs are lethargy hypotonia and seizures later the infants may develop athetoid cerebral palsy mentalretardation and deafness When neurological signs evident in the infant permanent damage has alreadyoccurred leading to death or long term disability Therefore management strategies are aimed at preventingkernicterus
Jaundice in the Healthy Term Newborn
April 2002 Page 12 of 20
Until recently these strategies suggested maintaining serum unconjugated bilirubin concentrations below 340micromolL (20 mgdL) in healthy term infants through the use of phototherapy or exchange transfusion (11) Whileexchange transfusions had been a frequent occurrence from the 1950s to the 1970s and may sometimes still berequired phototherapy has become the mainstay of medical management of hyperbilirubinemia since that time
The cases of kernicterus originally described occurred mainly in infants with hemolytic disease Higher serumunconjugated bilirubin concentrations may be safe in healthy term infants without hemolytic disease It is notpossible to predict at what level an individual infant may develop kernicterus
Several authors have expressed serious concerns over the approach of allowing higher serum unconjugatedbilirubin concentrations to occur before investigating and treating these term infants (11-16) Brown andJohnson (10) have reported 23 cases of kernicterus occurring since 1989 16 in term and seven in near terminfants In these infants peak unconjugated bilirubin concentrations of 375 to 860 micromolL (22 to 50 mgdL)were seen All but one infant was breastfed Other associations found in these infants with kernicterus weredehydration (seven infants) glucose-6-phosphate dehydrogenase (G6PD) deficiency (five infants) ABOalloimmunization (one infant) hemolysis of unknown cause (five infants) familial etiology (one infant) andotherwise unexplained early jaundice clinically evident before 24 h of age (six infants) Similar cases have beenreported by others (1718) Although many of these babies were subsequently found to have additional riskfactors these factors were not often identified at the time the baby was noted to be jaundiced
Since the introduction in the 1990s of the kinder gentler approach to the management of hyperbilirubinemia agreat deal of confusion has arisen about approaches to the management of hyperbilirubinemia in healthy terminfants This confusion has extended to the care of borderline preterm infants who have often been treated asterm infants A recently published international survey reported considerable variability in the approach tohyperbilirubinemia and the use of phototherapy among neonatal units worldwide (3)
PhototherapyThe goal of hyperbilirubinemia treatment is to avoid bilirubin concentrations that may result in kernicterusPhototherapy remains an effective therapeutic intervention that decreases bilirubin concentrations therebypreventing elevated bilirubin levels associated with permanent sequelae
The effectiveness of phototherapy is related to the area of skin exposed and the radiant energy and thewavelength of the light (19-23) Phototherapy acts on unconjugated bilirubin to a depth of 2 mm from theepidermis Phototherapy changes the bilirubin through structural photoisomerization into water-solublelumirubin that is excreted in the urine (19) The fall in bilirubin level is proportionately greater in the skin thanin the serum (20) Therefore the infant receiving phototherapy should have as much skin as possible exposed tothe lights More intense phototherapy may be achieved by using multiple sources of phototherapy double ortriple phototherapy is recommended to optimize the skin surface exposed and therefore the efficacy ofphototherapy More detailed discussion of the physics of phototherapy has been published (124) It is important to recognize the relationship between dehydration and hyperbilirubinemia Dehydration may beassociated with increased serum bilirubin concentrations and may be exacerbated by phototherapy Alljaundiced infants should be adequately hydrated before and during phototherapy Breastfeeding is notcontraindicated in the presence of hyperbilirubinemia and should be continued More frequent breastfeedingsmay be beneficial (25)
The concentrations of bilirubin at which phototherapy might be initiated in healthy term infants and those withrisk factors are shown in Figure 1 Guidelines for phototherapy in low birth weight infants remain as previouslypublished (1) The bilirubin concentrations at which phototherapy is suggested by the Canadian PaediatricSociety in the present statement are more conservative than the current recommendations of the AmericanAcademy of Pediatrics (2) If the infant is a healthy term newborn phototherapy should be started as indicated
Jaundice in the Healthy Term Newborn
April 2002 Page 13 of 20
in the upper curve of Figure 1 If the infant has one or more risk factors a clinical decision should be made toinitiate phototherapy at the concentration indicated by the lower curve
Figure 1 Guidelines for initiation of phototherapy for hyperbilirubinemia in term infants with and without riskfactors Some risk factors include gestional age younger than 37 weeks birth weight less than 2500 ghemolysis jaundice at younger than 24 h of age sepsis and the need for resuscitation at birth
The timely recognition of risk factors is essential to minimize the danger of kernicterus The risk factors are asfollows
bull gestational age younger than 37 weeks and birth weight less than 2500 g bull hemolysis due to maternal isoimmunization G6PD deficiency spherocytosis or other causes bull jaundice at less than 24 h of age bull sepsis and bull the need for resuscitation at birth
Jaundice in the Healthy Term Newborn
April 2002 Page 14 of 20
Clinical management of hyperbilirubinemia in infants
A bilirubin level that justifies consideration of phototherapy should mandate the investigation of the cause ofhyperbilirubinemia Investigation should include a clinically pertinent history of the mother family historydescription of labour and delivery and infantrsquos clinical course (26) A physical examination should besupplemented by laboratory investigations (Table 1) including determination of unconjugated and conjugatedserum bilirubin concentrations and blood group with direct antibody test (Coombsrsquo test) and hemoglobin andhematocrit levels A complete blood count including differential white cell count and a blood smear for red cellmorphology may be indicated Further tests (eg reticulocyte count G6PD screen) may be indicated based oninitial results ethnicity or clinical presentation Testing for serum electrolytes and albumin or protein areindicated in some situations such as suspected dehydration or when bilirubin levels approach exchange valuesIn the absence of drugs or clinical states that alter the binding of bilirubin by albumin the bilirubin to albuminor the bilirubin to protein ratio reflects the free bilirubin concentration and the binding capacity of the serum(27-29) At a bilirubin concentration close to exchange transfusion levels some clinicians may wish to ensurethat serum bilirubin binding is normal (albumin 25 gL or greater protein 54 gL or greater) Values belowthese levels may be associated with low bilirubin binding and may be used by the clinician when decidingwhether further intervention (eg exchange transfusion) should take place (27)
TABLE 1 Laboratory investigation for hyperbilirubinemia in term newborn infants
Indicated (if bilirubin concentrations reach phototherapy levels) Serum total or unconjugated bilirubin concentration Serum conjugated bilirubin concentration Blood group with direct antibody test (Coombsrsquo test) Hemoglobin and hematocrit determinations
Optional (in specific clinical circumstances) Complete blood count including manual differential white cell count Blood smear for red cell morphology Reticulocyte count Glucose-6-phosphate dehydrogenase screen Serum electrolytes and albumin or protein concentrations
For infants with prolonged jaundice (lasting longer than seven days) or with conjugated hyperbilirubinemia(greater than 30 micromolL) additional investigation and management may be required and a consultation with aspecialist may be needed (30)
During the past decade most nurseries have shortened the time of hospital stay for term healthy newborninfants Early discharge of neonates means that jaundice is not often recognized at discharge (31) The CanadianPaediatric Society reiterates the importance of allowing early discharge only if a healthy status is confirmed foreach baby and appropriate follow-up is provided (32) Appropriate parental education about feeding signs ofdehydration and jaundice must be implemented in hospital nurseries Testing for serum bilirubin concentrationsmust be readily available for newborns on an out-patient basis Readmission to hospital (usually the hospital ofbirth) may be necessary for the investigation and management of hyperbilirubinemia
Exchange transfusion If phototherapy fails to control the rising bilirubin levels exchange transfusion is indicated to lower serumbilirubin concentrations For healthy term infants without risk factors exchange transfusion should beconsidered at serum unconjugated bilirubin concentrations of 400 to 430 micromolL For term infants with riskfactors the level should be 340 micromolL For infants who initially present with serum bilirubin concentrations in
Jaundice in the Healthy Term Newborn
April 2002 Page 15 of 20
excess of exchange levels intensive phototherapy should produce a decline of serum unconjugated bilirubinfrom 20 to 35 micromolL within 4 to 6 h and levels should continue to fall thereafter and remain below thethreshold for exchange transfusion If the bilirubin concentration does not decrease after adequate rehydrationand 4 to 6 h of intensive phototherapy exchange transfusion should be considered Preparation for thisincluding ensuring availability of blood should occur shortly after the admission of babies whose bilirubinconcentrations exceed exchange levels Appropriate consultation should be obtained if the etiology ofhyperbilirubinemia is unclear the infant is ill and particularly if bilirubin concentrations are approachingexchange levels Because the risks of exchange transfusion are significant the best management may bereviewed with an expert opinion from a neonatologist
Conclusions Hyperbilirubinemia in apparently healthy term newborn infants continues to hold the potential threat ofcomplications from bilirubin encephalopathy and kernicterus Careful assessment of risk factors judicious useof phototherapy appropriate laboratory monitoring and specific treatment of other disorders (eg sepsis) areessential for the optimal management of hyperbilirubinemia Appropriate laboratory facilities must be availableto measure bilirubin concentrations for out-patients in required clinical situations Readmission to hospital maybe required if phototherapy is necessary Guidelines for phototherapy are presented for term babies with andwithout identifiable risk factors
References
1 Fetus and Newborn Committee Canadian Paediatric Society Use of phototherapy for neonatalhyperbilirubinemia Can Med Assoc J 19861341237-45 2 American Academy of Pediatrics Practice parameter Management of hyperbilirubinemia in the healthy termnewborn Pediatrics 199494558-65 3 Hansen TWR Therapeutical approaches to neonatal jaundice an international survey Clin Pediatr199635309-16 4 Valaes T Koliopoulos C Koltsidopoulos A The impact of phototherapy in the management of neonatalhyperbilirubinemia comparison of historical cohorts Acta Paediatrica 199685273-6 5 Gustafson PA Boyle DW Bilirubin index a new standard for intervention Med Hypotheses 199545409-16 6 Torres-Torres M Tayaba R Weintraub A Holzman IR New perspectives on neonatal hyperbilirubinemiaMount Sinai J Med 199461424-8 7 Lazar L Litwin A Merlob P Phototherapy for neonatal nonhemolytic hyperbilirubinemia analysis ofrebound and indications for discontinuing therapy Clin Pediatr 199332264-7 8 Newman TB Maisels MJ Evaluation and treatment of jaundice in the term newborn Pediatrics 199289809-18 9 McMillan DD Lockyer JM Magnan L Akierman A Parboosingh JT Effect of educational program andinterview on adoption of guidelines for the management of neonatal hyperbilirubinemia Can Med Assoc J1991144707-12 10 Brown AK Johnson L Loss of concern about jaundice and the reemergence of kernicterus in full-terminfants in the era of managed care In Fanaroff AA Klaus MH eds The Year Book of Neonatal and PerinatalMedicine Philadelphia Mosby Yearbook 199617-28 11 Valaes T Bilirubin toxicity The problem was solved a generation ago Pediatrics 199289819-21 12 Wennberg RP Bilirubin recommendations present problems New guidelines simplistic and untestedPediatrics 199289821-2 13 Merenstein GB lsquoNewrsquo bilirubin recommendations questioned Pediatrics 199289822-3 14 Poland RL In search of a lsquogold standardrsquo for bilirubin toxicity Pediatrics 199289823-4 15 Brown AK Seidman DS Stevenson DK Jaundice in healthy term neonates Do we need new action levelsor new approaches Pediatrics 199289827-9 16 Johnson L Yet another expert opinion on bilirubin toxicity Pediatrics 199289829-31
Jaundice in the Healthy Term Newborn
April 2002 Page 16 of 20
17 MacDonald MG Hidden risks Early discharge and bilirubin toxicity due to glucose-6-phosphatedehydrogenase deficiency Pediatrics 199596734-8 18 Maisels MJ Newman TB Kernicterus in otherwise healthy breast-fed newborns Pediatrics 199596730-3 19 Vogl TP Phototherapy of neonatal hyperbilirubinemia bilirubin in unexposed areas of the skin J Pediatr197485707-1020 Rubaltelli FF Carli M The effect of light on cutaneous bilirubin Biol Neonate 197118457-62 21 Sisson TR Kendall N Shaw E et al Phototherapy of jaundice in the newborn infant 2 Effect of variouslight intensities J Pediatr 19738135-8 22 Bonta BW Warshaw JB Importance of radiant flux in the treatment of hyperbilirubinemia failure ofoverhead phototherapy units in intensive care units Pediatrics 197657502-5 23 Warshaw JB Gagliardi J Patel A A comparison of fluorescent and non-fluorescent light source forphototherapy Pediatrics 198065795-8 24 Ennever JF Blue light green light white light more light treatment of neonatal jaundice Clin Perinatol199017467-8125 Auerbach KG Gartner LM Breastfeeding and human milk their association with jaundice in the neonateClin Perinatol 19871489-108 26 Maisels MJ Jaundice in the newborn Pediatr Rev 19823305-20 27 Ahlfors CE Criteria for exchange transfusion in jaundiced newborns Pediatrics 199493488-94 28 Odell GB Storey GNB Rosenberg LA Studies in kernicterus III The saturation of serum protein withbilirubin during neonatal life and its relationship to brain damage at 5 years J Pediatr 19707612-21 29 Wirth FH Goldberg KE Lubchenco LO The neurologic outcome of infants evaluated for unboundbilirubin Pediatr Res 19759385-91 30 Haber BA Lake AM Cholestatic jaundice in the newborn Clin Perinatol 199017483-506 31 Maisels MJ Newman TB Jaundice in full-term and near-term babies who leave the hospital within 36hours The pediatricianrsquos nemesis Clin Perinatol 199825295-302 32 Fetus and Newborn Committee Canadian Paediatric Society and Society of Obstetricians andGynaecologists of Canada Facilitating discharge home following a normal term birth Paediatr Child Health19961165-8
Fetus and Newborn Committee Members Drs John Watts Department of Paediatrics Childrenrsquos Hospital ndash Hamilton Health Sciences CentreHamilton Ontario (director responsible) Douglas McMillan Department of Pediatrics Foothills HospitalCalgary Alberta (chair) Arne Ohlsson Department of Paediatrics Mount Sinai Hospital Toronto Ontario(co-chair) Deborah Davis Childrenrsquos Hospital of Eastern Ontario Ottawa Ontario Daniel Faucher RoyalVictoria Hospital Montreal Quebec (principal author) John Van Aerde Stollery Childrenrsquos Health CentreEdmonton Alberta Michael Vincer IWK-Grace Health Centre Halifax Nova ScotiaConsultant Dr Michael C Klein University of British Columbia Vancouver British Columbia (College ofFamily Physicians of Canada)Liaisons Drs James Lemon Riley Childrenrsquos Hospital Indiana University Medical Center IndianapolisIndiana (American Academy of Pediatrics) Saroj Saigal Department of Paediatrics McMaster UniversityMedical Centre Childrenrsquos Hospital ndash Hamilton Health Sciences Centre Hamilton Ontario (CPS Neonatal-Perinatal Medicine Section) Cheryl Levitt Department of Family Medicine Childrenrsquos Hospital ndash HamiltonHealth Sciences Centre Hamilton Ontario (College of Family Physicians of Canada) Catherine McCourtDirector Bureau of Reproductive amp Child Health Laboratory Centre for Disease Control Ottawa Ontario(Health Canada) Mrs Debbie Fraser-Askin Winnipeg Manitoba (Neonatal Nurses) Dr Line LeducDepartment of Obstetrics-Gynecology Hocircpital Sainte-Justine Montreal Quebec (Society of Obstetricians andGynaecologists of Canada)
Disclaimer The recommendations in this position statement do not indicate an exclusive course oftreatment or procedure to be followed Variations taking into account individual circumstances may beappropriate
Jaundice in the Healthy Term Newborn
April 2002 Page 17 of 20
APPENDIX 3Hyperbilirubinemia Risk Designation for Term and Near-Term Well Newborns
Jaundice in the Healthy Term Newborn
April 2002 Page 18 of 20
APPENDIX 4
American Academy of Pediatrics 1994 Practice parameter Management ofHyperbilirubinemia in the Healthy Term Newborn Pediatrics 94(4) 558-565
(Chart and Algorithm)
Jaundice in the Healthy Term Newborn
April 2002 Page 19 of 20
AlgorithmPediatric clinician evaluatesterm newborn with jaundice
Does the infant have signs of underlyingserious illness (lethargy apnea tachypneatemperature instability behavior changeshepatosplenomegaly persistant vomiting
or persistent feeding difficulty)
1
2
Exit this algorithm to individualizedclinical evaluation including
assessment of jaundice and underlyingdisease
Yes
3
No
Is the infant lt 37 weeks gestational age
4 Exit this algorithm to individualizedclinical evaluation including
assessment of jaundice in light ofprematurity
5
Yes
Is the mothersABO and Rh
blood typing andisoimmune
antibody screenstatus known
Is the mothersblood Rhpositive
Does themothers blood
have anyimmune
antibodies
Consider holding the infantscord blood in the blood bank incase future testing is necessary
6 7 8 9No
Yes Yes No
(Go to Box 10) (Go to Box 10) (Go to Box 10) (Go to Box 13)
No No Yes
Perform blood typing (ABO and Rh) and direct Coombs testingon the infants cord (preferably) or venous blood
10
Is the infantsblood direct
Coombs testpositive
Exit this algorithm to individualized clinical evaluationincluding assessment of jaundice and isoimmune
hemolytic disease
11 12
Yes
Are any of the following risk factors present tosuggest that nonisoimmune hemolytic disease
is possible in this infant(1) Family history of hemolytic anemia
OR(2) Family history of early or severe jaundice
OR(3) Ethnicity or geographic originassociated with hemolytic anemia
OR(4) Early or severe jaundice
Perform appropriate laboratoryassessment of infant including
(but not limited to consideration of)(1) Complete blood count differentialsmear reticulocyte count(2) G6PD screen(3) Hemoglobin electrophoresis
1314
No
No
No
(Go to Box 16)
Does the evaluation suggesthemolytic disease
15
Yes
(Go to Box 17)(Go to Box 16)
No
Jaundice in the Healthy Term Newborn
April 2002 Page 20 of 20
AlgorithmIs the infant
jaundiced andlt 24 hours of
age
Exit this algorithm to individualizedclinical evaluation includingassessment of jaundice and
nonisoimmune hemolytic disease
Is jaundiceclinicallysignificant by medical
judgment
(1) Measure infantstotal serum bilirubin(2) Go to Box 27
Healthy term infant with jaundice not clinicallysignificant by medical judgment
Follow infant in routine clinical supervision
1617
18 19
20
21
(Go to Box 22)
Yes
Yes
No
No
Is jaundicepersisting
gt 2 weeks
Does this infant haveabnormal physicalexam results dark
urine or light stools
Is jaundice persistinggt 3 weeks
Perform appropriate physical andlaboratory assessment of theinfant including possibility of
cholestatic jaundice
Provide routine carerecommend routine
feeding and follow-up Table 2 Management of Hyperbilirubinemia in the Healthy Term NewbornAgehours TSB Level mgdL (umolL)
Consider Phototherapy Exchange ExchangePhototherapy Transfusion Transfusion
if Intensive and IntensivePhototherapy PhototherapyFails
lt24 25-48 gt 12 (170) gt15 (260) gt 20 (340) gt 25 (430)49-72 gt 15 (260) gt 18 (310) gt 25 (430) gt 30 (510)gt 72 gt 17 (290) gt 20 (340) gt 25 (430) gt 30 (510)
TSB indicates total serum bilirubinPhototherapy at these TSB levels is a clinical option meaning that the intervention is availableand may be used on the basis of individual clinical judgement For a more detailed descriptionof phototherapy see the AppendixIntensive phototherapy (Appendix) should produce a decline of TSB of 1 to 2 mgdL within 4 to 6hours and the TSB level should continue to fall and remain below the threshold level for exchangetransfusion If this does not occur it is considered a failure of phototherapyTerm infants who are clinically jaundiced at lt 24 hours old are not considered healthy andrequire further evaluation (see text)
22 23
24
25
26
YesYes
No
YesNo
No 27
Algorithm Management of hyperbilirubinemia inthe healthy term infant
(From Box 19)
Jaundice in the Healthy Term Newborn
April 2002 Page 10 of 20
Management of Newborn Jaundice at Home Program
Referral for the Healthy Term Infant
PHN Identifies jaundice in the newborn
1 Preterm Infant RhABO incompatibility2 Look or act ill (eg lethargic apnea tachycardia
temperature unstable poor feeding changed behaviorpersistant vomiting insufficient voidingstooling)
No
Family hx of early or severejaundice Ethnicity relevant(Mediterranean SE Asian)
No
Infant less than24 hrs
No
Is jaundiceclinically
significant
No
Jaundice persistedgt 2 weeks
Jaundice gt3weeks
Routinecare and
feedsNo
Routinecare and
feedsNo
RoutineClinical
Supervis-ion
No
Refer to MD ASAPYes
Refer to MD forinvestigationeg
G6PD SpherocytosisYes
Refer to MD fornon - isoimmune
hemolyticdisease
investigation
Yes
Refer to MD forfollow-up with total
serum bilirubinYes
Any abnormal physicalfindings Dark urine
light stoolsRefer to MDYes Yes
Refer to MDYes
APPENDIX 1 (Example)
Developed by the Coordinated Maternity Standards Committee South FraserHealth Region and Dr K Danso Pediatrician Surrey Memorial Hospital
Revised 1997 Copied with permission
Jaundice in the Healthy Term Newborn
April 2002 Page 11 of 20
APPENDIX 2
Approach to the Management of Hyperbilirubinemiain Term Newborn Infants
A Joint Statement with the College of Family Physicians of CanadaPaediatrics amp Child Health 19994(2)161-164Reference No FN98-02Reaffirmed February 2001
Reprints of this position statement are available from the Canadian Paediatric Society100-2204 Walkley Road Ottawa ON K1G 4G8 phone (613) 526-9397 fax (613) 526-3332
Contents bull Background bull Phototherapy bull Clinical management of hyperbilirubinemia in infants bull Exchange transfusion bull Conclusions bull References
Conflicting reports have led to confusion about the optimal management of jaundice in otherwise healthy terminfants (1-9) The lsquokinder gentler approachrsquo to neonatal hyperbilirubinemia proposed in 1992 by Newman andMaisels (8) resulted in a 1994 statement by the American Academy of Pediatrics (2) that addressed themanagement of healthy term infant without risk factors Recently there has been an increase in the number ofterm infants reported with kernicterus (10) It is important to note that while some of the infants reported withkernicterus had features that would place them in a high risk category some presented with severe jaundiceonly and no identifiable risk factors (10) The infants reported were commonly breastfed and frequentlydischarged from hospital very soon after birth (10) Nonetheless the current standards (2) for the managementof hyperbilirubinemia in the healthy term infant have become controversial This document updates information previously published by the Canadian Paediatric Society (1) It provides anoverview of the proposed management of hyperbilirubinemia based on available evidence even thoughrandomized controlled trials are not available to allow a conclusive assessment of the risk associated withhyperbilirubinemia in the clinical situations encountered in practice The objective of this overview is toestablish a management plan that will minimize the risk of kernicterus in term infants both with and withoutrisk factors Although scientific evidence has not established a clear link between specific bilirubinconcentrations and the development of kernicterus in healthy term babies information to date has beenincorporated into the following guidelines Background
Kernicterus is a neurological condition characterized by deep yellow staining of the basal nuclei Theaccompanying clinical syndrome results from the destructive changes of these neuronal populations Initiallythe signs are lethargy hypotonia and seizures later the infants may develop athetoid cerebral palsy mentalretardation and deafness When neurological signs evident in the infant permanent damage has alreadyoccurred leading to death or long term disability Therefore management strategies are aimed at preventingkernicterus
Jaundice in the Healthy Term Newborn
April 2002 Page 12 of 20
Until recently these strategies suggested maintaining serum unconjugated bilirubin concentrations below 340micromolL (20 mgdL) in healthy term infants through the use of phototherapy or exchange transfusion (11) Whileexchange transfusions had been a frequent occurrence from the 1950s to the 1970s and may sometimes still berequired phototherapy has become the mainstay of medical management of hyperbilirubinemia since that time
The cases of kernicterus originally described occurred mainly in infants with hemolytic disease Higher serumunconjugated bilirubin concentrations may be safe in healthy term infants without hemolytic disease It is notpossible to predict at what level an individual infant may develop kernicterus
Several authors have expressed serious concerns over the approach of allowing higher serum unconjugatedbilirubin concentrations to occur before investigating and treating these term infants (11-16) Brown andJohnson (10) have reported 23 cases of kernicterus occurring since 1989 16 in term and seven in near terminfants In these infants peak unconjugated bilirubin concentrations of 375 to 860 micromolL (22 to 50 mgdL)were seen All but one infant was breastfed Other associations found in these infants with kernicterus weredehydration (seven infants) glucose-6-phosphate dehydrogenase (G6PD) deficiency (five infants) ABOalloimmunization (one infant) hemolysis of unknown cause (five infants) familial etiology (one infant) andotherwise unexplained early jaundice clinically evident before 24 h of age (six infants) Similar cases have beenreported by others (1718) Although many of these babies were subsequently found to have additional riskfactors these factors were not often identified at the time the baby was noted to be jaundiced
Since the introduction in the 1990s of the kinder gentler approach to the management of hyperbilirubinemia agreat deal of confusion has arisen about approaches to the management of hyperbilirubinemia in healthy terminfants This confusion has extended to the care of borderline preterm infants who have often been treated asterm infants A recently published international survey reported considerable variability in the approach tohyperbilirubinemia and the use of phototherapy among neonatal units worldwide (3)
PhototherapyThe goal of hyperbilirubinemia treatment is to avoid bilirubin concentrations that may result in kernicterusPhototherapy remains an effective therapeutic intervention that decreases bilirubin concentrations therebypreventing elevated bilirubin levels associated with permanent sequelae
The effectiveness of phototherapy is related to the area of skin exposed and the radiant energy and thewavelength of the light (19-23) Phototherapy acts on unconjugated bilirubin to a depth of 2 mm from theepidermis Phototherapy changes the bilirubin through structural photoisomerization into water-solublelumirubin that is excreted in the urine (19) The fall in bilirubin level is proportionately greater in the skin thanin the serum (20) Therefore the infant receiving phototherapy should have as much skin as possible exposed tothe lights More intense phototherapy may be achieved by using multiple sources of phototherapy double ortriple phototherapy is recommended to optimize the skin surface exposed and therefore the efficacy ofphototherapy More detailed discussion of the physics of phototherapy has been published (124) It is important to recognize the relationship between dehydration and hyperbilirubinemia Dehydration may beassociated with increased serum bilirubin concentrations and may be exacerbated by phototherapy Alljaundiced infants should be adequately hydrated before and during phototherapy Breastfeeding is notcontraindicated in the presence of hyperbilirubinemia and should be continued More frequent breastfeedingsmay be beneficial (25)
The concentrations of bilirubin at which phototherapy might be initiated in healthy term infants and those withrisk factors are shown in Figure 1 Guidelines for phototherapy in low birth weight infants remain as previouslypublished (1) The bilirubin concentrations at which phototherapy is suggested by the Canadian PaediatricSociety in the present statement are more conservative than the current recommendations of the AmericanAcademy of Pediatrics (2) If the infant is a healthy term newborn phototherapy should be started as indicated
Jaundice in the Healthy Term Newborn
April 2002 Page 13 of 20
in the upper curve of Figure 1 If the infant has one or more risk factors a clinical decision should be made toinitiate phototherapy at the concentration indicated by the lower curve
Figure 1 Guidelines for initiation of phototherapy for hyperbilirubinemia in term infants with and without riskfactors Some risk factors include gestional age younger than 37 weeks birth weight less than 2500 ghemolysis jaundice at younger than 24 h of age sepsis and the need for resuscitation at birth
The timely recognition of risk factors is essential to minimize the danger of kernicterus The risk factors are asfollows
bull gestational age younger than 37 weeks and birth weight less than 2500 g bull hemolysis due to maternal isoimmunization G6PD deficiency spherocytosis or other causes bull jaundice at less than 24 h of age bull sepsis and bull the need for resuscitation at birth
Jaundice in the Healthy Term Newborn
April 2002 Page 14 of 20
Clinical management of hyperbilirubinemia in infants
A bilirubin level that justifies consideration of phototherapy should mandate the investigation of the cause ofhyperbilirubinemia Investigation should include a clinically pertinent history of the mother family historydescription of labour and delivery and infantrsquos clinical course (26) A physical examination should besupplemented by laboratory investigations (Table 1) including determination of unconjugated and conjugatedserum bilirubin concentrations and blood group with direct antibody test (Coombsrsquo test) and hemoglobin andhematocrit levels A complete blood count including differential white cell count and a blood smear for red cellmorphology may be indicated Further tests (eg reticulocyte count G6PD screen) may be indicated based oninitial results ethnicity or clinical presentation Testing for serum electrolytes and albumin or protein areindicated in some situations such as suspected dehydration or when bilirubin levels approach exchange valuesIn the absence of drugs or clinical states that alter the binding of bilirubin by albumin the bilirubin to albuminor the bilirubin to protein ratio reflects the free bilirubin concentration and the binding capacity of the serum(27-29) At a bilirubin concentration close to exchange transfusion levels some clinicians may wish to ensurethat serum bilirubin binding is normal (albumin 25 gL or greater protein 54 gL or greater) Values belowthese levels may be associated with low bilirubin binding and may be used by the clinician when decidingwhether further intervention (eg exchange transfusion) should take place (27)
TABLE 1 Laboratory investigation for hyperbilirubinemia in term newborn infants
Indicated (if bilirubin concentrations reach phototherapy levels) Serum total or unconjugated bilirubin concentration Serum conjugated bilirubin concentration Blood group with direct antibody test (Coombsrsquo test) Hemoglobin and hematocrit determinations
Optional (in specific clinical circumstances) Complete blood count including manual differential white cell count Blood smear for red cell morphology Reticulocyte count Glucose-6-phosphate dehydrogenase screen Serum electrolytes and albumin or protein concentrations
For infants with prolonged jaundice (lasting longer than seven days) or with conjugated hyperbilirubinemia(greater than 30 micromolL) additional investigation and management may be required and a consultation with aspecialist may be needed (30)
During the past decade most nurseries have shortened the time of hospital stay for term healthy newborninfants Early discharge of neonates means that jaundice is not often recognized at discharge (31) The CanadianPaediatric Society reiterates the importance of allowing early discharge only if a healthy status is confirmed foreach baby and appropriate follow-up is provided (32) Appropriate parental education about feeding signs ofdehydration and jaundice must be implemented in hospital nurseries Testing for serum bilirubin concentrationsmust be readily available for newborns on an out-patient basis Readmission to hospital (usually the hospital ofbirth) may be necessary for the investigation and management of hyperbilirubinemia
Exchange transfusion If phototherapy fails to control the rising bilirubin levels exchange transfusion is indicated to lower serumbilirubin concentrations For healthy term infants without risk factors exchange transfusion should beconsidered at serum unconjugated bilirubin concentrations of 400 to 430 micromolL For term infants with riskfactors the level should be 340 micromolL For infants who initially present with serum bilirubin concentrations in
Jaundice in the Healthy Term Newborn
April 2002 Page 15 of 20
excess of exchange levels intensive phototherapy should produce a decline of serum unconjugated bilirubinfrom 20 to 35 micromolL within 4 to 6 h and levels should continue to fall thereafter and remain below thethreshold for exchange transfusion If the bilirubin concentration does not decrease after adequate rehydrationand 4 to 6 h of intensive phototherapy exchange transfusion should be considered Preparation for thisincluding ensuring availability of blood should occur shortly after the admission of babies whose bilirubinconcentrations exceed exchange levels Appropriate consultation should be obtained if the etiology ofhyperbilirubinemia is unclear the infant is ill and particularly if bilirubin concentrations are approachingexchange levels Because the risks of exchange transfusion are significant the best management may bereviewed with an expert opinion from a neonatologist
Conclusions Hyperbilirubinemia in apparently healthy term newborn infants continues to hold the potential threat ofcomplications from bilirubin encephalopathy and kernicterus Careful assessment of risk factors judicious useof phototherapy appropriate laboratory monitoring and specific treatment of other disorders (eg sepsis) areessential for the optimal management of hyperbilirubinemia Appropriate laboratory facilities must be availableto measure bilirubin concentrations for out-patients in required clinical situations Readmission to hospital maybe required if phototherapy is necessary Guidelines for phototherapy are presented for term babies with andwithout identifiable risk factors
References
1 Fetus and Newborn Committee Canadian Paediatric Society Use of phototherapy for neonatalhyperbilirubinemia Can Med Assoc J 19861341237-45 2 American Academy of Pediatrics Practice parameter Management of hyperbilirubinemia in the healthy termnewborn Pediatrics 199494558-65 3 Hansen TWR Therapeutical approaches to neonatal jaundice an international survey Clin Pediatr199635309-16 4 Valaes T Koliopoulos C Koltsidopoulos A The impact of phototherapy in the management of neonatalhyperbilirubinemia comparison of historical cohorts Acta Paediatrica 199685273-6 5 Gustafson PA Boyle DW Bilirubin index a new standard for intervention Med Hypotheses 199545409-16 6 Torres-Torres M Tayaba R Weintraub A Holzman IR New perspectives on neonatal hyperbilirubinemiaMount Sinai J Med 199461424-8 7 Lazar L Litwin A Merlob P Phototherapy for neonatal nonhemolytic hyperbilirubinemia analysis ofrebound and indications for discontinuing therapy Clin Pediatr 199332264-7 8 Newman TB Maisels MJ Evaluation and treatment of jaundice in the term newborn Pediatrics 199289809-18 9 McMillan DD Lockyer JM Magnan L Akierman A Parboosingh JT Effect of educational program andinterview on adoption of guidelines for the management of neonatal hyperbilirubinemia Can Med Assoc J1991144707-12 10 Brown AK Johnson L Loss of concern about jaundice and the reemergence of kernicterus in full-terminfants in the era of managed care In Fanaroff AA Klaus MH eds The Year Book of Neonatal and PerinatalMedicine Philadelphia Mosby Yearbook 199617-28 11 Valaes T Bilirubin toxicity The problem was solved a generation ago Pediatrics 199289819-21 12 Wennberg RP Bilirubin recommendations present problems New guidelines simplistic and untestedPediatrics 199289821-2 13 Merenstein GB lsquoNewrsquo bilirubin recommendations questioned Pediatrics 199289822-3 14 Poland RL In search of a lsquogold standardrsquo for bilirubin toxicity Pediatrics 199289823-4 15 Brown AK Seidman DS Stevenson DK Jaundice in healthy term neonates Do we need new action levelsor new approaches Pediatrics 199289827-9 16 Johnson L Yet another expert opinion on bilirubin toxicity Pediatrics 199289829-31
Jaundice in the Healthy Term Newborn
April 2002 Page 16 of 20
17 MacDonald MG Hidden risks Early discharge and bilirubin toxicity due to glucose-6-phosphatedehydrogenase deficiency Pediatrics 199596734-8 18 Maisels MJ Newman TB Kernicterus in otherwise healthy breast-fed newborns Pediatrics 199596730-3 19 Vogl TP Phototherapy of neonatal hyperbilirubinemia bilirubin in unexposed areas of the skin J Pediatr197485707-1020 Rubaltelli FF Carli M The effect of light on cutaneous bilirubin Biol Neonate 197118457-62 21 Sisson TR Kendall N Shaw E et al Phototherapy of jaundice in the newborn infant 2 Effect of variouslight intensities J Pediatr 19738135-8 22 Bonta BW Warshaw JB Importance of radiant flux in the treatment of hyperbilirubinemia failure ofoverhead phototherapy units in intensive care units Pediatrics 197657502-5 23 Warshaw JB Gagliardi J Patel A A comparison of fluorescent and non-fluorescent light source forphototherapy Pediatrics 198065795-8 24 Ennever JF Blue light green light white light more light treatment of neonatal jaundice Clin Perinatol199017467-8125 Auerbach KG Gartner LM Breastfeeding and human milk their association with jaundice in the neonateClin Perinatol 19871489-108 26 Maisels MJ Jaundice in the newborn Pediatr Rev 19823305-20 27 Ahlfors CE Criteria for exchange transfusion in jaundiced newborns Pediatrics 199493488-94 28 Odell GB Storey GNB Rosenberg LA Studies in kernicterus III The saturation of serum protein withbilirubin during neonatal life and its relationship to brain damage at 5 years J Pediatr 19707612-21 29 Wirth FH Goldberg KE Lubchenco LO The neurologic outcome of infants evaluated for unboundbilirubin Pediatr Res 19759385-91 30 Haber BA Lake AM Cholestatic jaundice in the newborn Clin Perinatol 199017483-506 31 Maisels MJ Newman TB Jaundice in full-term and near-term babies who leave the hospital within 36hours The pediatricianrsquos nemesis Clin Perinatol 199825295-302 32 Fetus and Newborn Committee Canadian Paediatric Society and Society of Obstetricians andGynaecologists of Canada Facilitating discharge home following a normal term birth Paediatr Child Health19961165-8
Fetus and Newborn Committee Members Drs John Watts Department of Paediatrics Childrenrsquos Hospital ndash Hamilton Health Sciences CentreHamilton Ontario (director responsible) Douglas McMillan Department of Pediatrics Foothills HospitalCalgary Alberta (chair) Arne Ohlsson Department of Paediatrics Mount Sinai Hospital Toronto Ontario(co-chair) Deborah Davis Childrenrsquos Hospital of Eastern Ontario Ottawa Ontario Daniel Faucher RoyalVictoria Hospital Montreal Quebec (principal author) John Van Aerde Stollery Childrenrsquos Health CentreEdmonton Alberta Michael Vincer IWK-Grace Health Centre Halifax Nova ScotiaConsultant Dr Michael C Klein University of British Columbia Vancouver British Columbia (College ofFamily Physicians of Canada)Liaisons Drs James Lemon Riley Childrenrsquos Hospital Indiana University Medical Center IndianapolisIndiana (American Academy of Pediatrics) Saroj Saigal Department of Paediatrics McMaster UniversityMedical Centre Childrenrsquos Hospital ndash Hamilton Health Sciences Centre Hamilton Ontario (CPS Neonatal-Perinatal Medicine Section) Cheryl Levitt Department of Family Medicine Childrenrsquos Hospital ndash HamiltonHealth Sciences Centre Hamilton Ontario (College of Family Physicians of Canada) Catherine McCourtDirector Bureau of Reproductive amp Child Health Laboratory Centre for Disease Control Ottawa Ontario(Health Canada) Mrs Debbie Fraser-Askin Winnipeg Manitoba (Neonatal Nurses) Dr Line LeducDepartment of Obstetrics-Gynecology Hocircpital Sainte-Justine Montreal Quebec (Society of Obstetricians andGynaecologists of Canada)
Disclaimer The recommendations in this position statement do not indicate an exclusive course oftreatment or procedure to be followed Variations taking into account individual circumstances may beappropriate
Jaundice in the Healthy Term Newborn
April 2002 Page 17 of 20
APPENDIX 3Hyperbilirubinemia Risk Designation for Term and Near-Term Well Newborns
Jaundice in the Healthy Term Newborn
April 2002 Page 18 of 20
APPENDIX 4
American Academy of Pediatrics 1994 Practice parameter Management ofHyperbilirubinemia in the Healthy Term Newborn Pediatrics 94(4) 558-565
(Chart and Algorithm)
Jaundice in the Healthy Term Newborn
April 2002 Page 19 of 20
AlgorithmPediatric clinician evaluatesterm newborn with jaundice
Does the infant have signs of underlyingserious illness (lethargy apnea tachypneatemperature instability behavior changeshepatosplenomegaly persistant vomiting
or persistent feeding difficulty)
1
2
Exit this algorithm to individualizedclinical evaluation including
assessment of jaundice and underlyingdisease
Yes
3
No
Is the infant lt 37 weeks gestational age
4 Exit this algorithm to individualizedclinical evaluation including
assessment of jaundice in light ofprematurity
5
Yes
Is the mothersABO and Rh
blood typing andisoimmune
antibody screenstatus known
Is the mothersblood Rhpositive
Does themothers blood
have anyimmune
antibodies
Consider holding the infantscord blood in the blood bank incase future testing is necessary
6 7 8 9No
Yes Yes No
(Go to Box 10) (Go to Box 10) (Go to Box 10) (Go to Box 13)
No No Yes
Perform blood typing (ABO and Rh) and direct Coombs testingon the infants cord (preferably) or venous blood
10
Is the infantsblood direct
Coombs testpositive
Exit this algorithm to individualized clinical evaluationincluding assessment of jaundice and isoimmune
hemolytic disease
11 12
Yes
Are any of the following risk factors present tosuggest that nonisoimmune hemolytic disease
is possible in this infant(1) Family history of hemolytic anemia
OR(2) Family history of early or severe jaundice
OR(3) Ethnicity or geographic originassociated with hemolytic anemia
OR(4) Early or severe jaundice
Perform appropriate laboratoryassessment of infant including
(but not limited to consideration of)(1) Complete blood count differentialsmear reticulocyte count(2) G6PD screen(3) Hemoglobin electrophoresis
1314
No
No
No
(Go to Box 16)
Does the evaluation suggesthemolytic disease
15
Yes
(Go to Box 17)(Go to Box 16)
No
Jaundice in the Healthy Term Newborn
April 2002 Page 20 of 20
AlgorithmIs the infant
jaundiced andlt 24 hours of
age
Exit this algorithm to individualizedclinical evaluation includingassessment of jaundice and
nonisoimmune hemolytic disease
Is jaundiceclinicallysignificant by medical
judgment
(1) Measure infantstotal serum bilirubin(2) Go to Box 27
Healthy term infant with jaundice not clinicallysignificant by medical judgment
Follow infant in routine clinical supervision
1617
18 19
20
21
(Go to Box 22)
Yes
Yes
No
No
Is jaundicepersisting
gt 2 weeks
Does this infant haveabnormal physicalexam results dark
urine or light stools
Is jaundice persistinggt 3 weeks
Perform appropriate physical andlaboratory assessment of theinfant including possibility of
cholestatic jaundice
Provide routine carerecommend routine
feeding and follow-up Table 2 Management of Hyperbilirubinemia in the Healthy Term NewbornAgehours TSB Level mgdL (umolL)
Consider Phototherapy Exchange ExchangePhototherapy Transfusion Transfusion
if Intensive and IntensivePhototherapy PhototherapyFails
lt24 25-48 gt 12 (170) gt15 (260) gt 20 (340) gt 25 (430)49-72 gt 15 (260) gt 18 (310) gt 25 (430) gt 30 (510)gt 72 gt 17 (290) gt 20 (340) gt 25 (430) gt 30 (510)
TSB indicates total serum bilirubinPhototherapy at these TSB levels is a clinical option meaning that the intervention is availableand may be used on the basis of individual clinical judgement For a more detailed descriptionof phototherapy see the AppendixIntensive phototherapy (Appendix) should produce a decline of TSB of 1 to 2 mgdL within 4 to 6hours and the TSB level should continue to fall and remain below the threshold level for exchangetransfusion If this does not occur it is considered a failure of phototherapyTerm infants who are clinically jaundiced at lt 24 hours old are not considered healthy andrequire further evaluation (see text)
22 23
24
25
26
YesYes
No
YesNo
No 27
Algorithm Management of hyperbilirubinemia inthe healthy term infant
(From Box 19)
Jaundice in the Healthy Term Newborn
April 2002 Page 11 of 20
APPENDIX 2
Approach to the Management of Hyperbilirubinemiain Term Newborn Infants
A Joint Statement with the College of Family Physicians of CanadaPaediatrics amp Child Health 19994(2)161-164Reference No FN98-02Reaffirmed February 2001
Reprints of this position statement are available from the Canadian Paediatric Society100-2204 Walkley Road Ottawa ON K1G 4G8 phone (613) 526-9397 fax (613) 526-3332
Contents bull Background bull Phototherapy bull Clinical management of hyperbilirubinemia in infants bull Exchange transfusion bull Conclusions bull References
Conflicting reports have led to confusion about the optimal management of jaundice in otherwise healthy terminfants (1-9) The lsquokinder gentler approachrsquo to neonatal hyperbilirubinemia proposed in 1992 by Newman andMaisels (8) resulted in a 1994 statement by the American Academy of Pediatrics (2) that addressed themanagement of healthy term infant without risk factors Recently there has been an increase in the number ofterm infants reported with kernicterus (10) It is important to note that while some of the infants reported withkernicterus had features that would place them in a high risk category some presented with severe jaundiceonly and no identifiable risk factors (10) The infants reported were commonly breastfed and frequentlydischarged from hospital very soon after birth (10) Nonetheless the current standards (2) for the managementof hyperbilirubinemia in the healthy term infant have become controversial This document updates information previously published by the Canadian Paediatric Society (1) It provides anoverview of the proposed management of hyperbilirubinemia based on available evidence even thoughrandomized controlled trials are not available to allow a conclusive assessment of the risk associated withhyperbilirubinemia in the clinical situations encountered in practice The objective of this overview is toestablish a management plan that will minimize the risk of kernicterus in term infants both with and withoutrisk factors Although scientific evidence has not established a clear link between specific bilirubinconcentrations and the development of kernicterus in healthy term babies information to date has beenincorporated into the following guidelines Background
Kernicterus is a neurological condition characterized by deep yellow staining of the basal nuclei Theaccompanying clinical syndrome results from the destructive changes of these neuronal populations Initiallythe signs are lethargy hypotonia and seizures later the infants may develop athetoid cerebral palsy mentalretardation and deafness When neurological signs evident in the infant permanent damage has alreadyoccurred leading to death or long term disability Therefore management strategies are aimed at preventingkernicterus
Jaundice in the Healthy Term Newborn
April 2002 Page 12 of 20
Until recently these strategies suggested maintaining serum unconjugated bilirubin concentrations below 340micromolL (20 mgdL) in healthy term infants through the use of phototherapy or exchange transfusion (11) Whileexchange transfusions had been a frequent occurrence from the 1950s to the 1970s and may sometimes still berequired phototherapy has become the mainstay of medical management of hyperbilirubinemia since that time
The cases of kernicterus originally described occurred mainly in infants with hemolytic disease Higher serumunconjugated bilirubin concentrations may be safe in healthy term infants without hemolytic disease It is notpossible to predict at what level an individual infant may develop kernicterus
Several authors have expressed serious concerns over the approach of allowing higher serum unconjugatedbilirubin concentrations to occur before investigating and treating these term infants (11-16) Brown andJohnson (10) have reported 23 cases of kernicterus occurring since 1989 16 in term and seven in near terminfants In these infants peak unconjugated bilirubin concentrations of 375 to 860 micromolL (22 to 50 mgdL)were seen All but one infant was breastfed Other associations found in these infants with kernicterus weredehydration (seven infants) glucose-6-phosphate dehydrogenase (G6PD) deficiency (five infants) ABOalloimmunization (one infant) hemolysis of unknown cause (five infants) familial etiology (one infant) andotherwise unexplained early jaundice clinically evident before 24 h of age (six infants) Similar cases have beenreported by others (1718) Although many of these babies were subsequently found to have additional riskfactors these factors were not often identified at the time the baby was noted to be jaundiced
Since the introduction in the 1990s of the kinder gentler approach to the management of hyperbilirubinemia agreat deal of confusion has arisen about approaches to the management of hyperbilirubinemia in healthy terminfants This confusion has extended to the care of borderline preterm infants who have often been treated asterm infants A recently published international survey reported considerable variability in the approach tohyperbilirubinemia and the use of phototherapy among neonatal units worldwide (3)
PhototherapyThe goal of hyperbilirubinemia treatment is to avoid bilirubin concentrations that may result in kernicterusPhototherapy remains an effective therapeutic intervention that decreases bilirubin concentrations therebypreventing elevated bilirubin levels associated with permanent sequelae
The effectiveness of phototherapy is related to the area of skin exposed and the radiant energy and thewavelength of the light (19-23) Phototherapy acts on unconjugated bilirubin to a depth of 2 mm from theepidermis Phototherapy changes the bilirubin through structural photoisomerization into water-solublelumirubin that is excreted in the urine (19) The fall in bilirubin level is proportionately greater in the skin thanin the serum (20) Therefore the infant receiving phototherapy should have as much skin as possible exposed tothe lights More intense phototherapy may be achieved by using multiple sources of phototherapy double ortriple phototherapy is recommended to optimize the skin surface exposed and therefore the efficacy ofphototherapy More detailed discussion of the physics of phototherapy has been published (124) It is important to recognize the relationship between dehydration and hyperbilirubinemia Dehydration may beassociated with increased serum bilirubin concentrations and may be exacerbated by phototherapy Alljaundiced infants should be adequately hydrated before and during phototherapy Breastfeeding is notcontraindicated in the presence of hyperbilirubinemia and should be continued More frequent breastfeedingsmay be beneficial (25)
The concentrations of bilirubin at which phototherapy might be initiated in healthy term infants and those withrisk factors are shown in Figure 1 Guidelines for phototherapy in low birth weight infants remain as previouslypublished (1) The bilirubin concentrations at which phototherapy is suggested by the Canadian PaediatricSociety in the present statement are more conservative than the current recommendations of the AmericanAcademy of Pediatrics (2) If the infant is a healthy term newborn phototherapy should be started as indicated
Jaundice in the Healthy Term Newborn
April 2002 Page 13 of 20
in the upper curve of Figure 1 If the infant has one or more risk factors a clinical decision should be made toinitiate phototherapy at the concentration indicated by the lower curve
Figure 1 Guidelines for initiation of phototherapy for hyperbilirubinemia in term infants with and without riskfactors Some risk factors include gestional age younger than 37 weeks birth weight less than 2500 ghemolysis jaundice at younger than 24 h of age sepsis and the need for resuscitation at birth
The timely recognition of risk factors is essential to minimize the danger of kernicterus The risk factors are asfollows
bull gestational age younger than 37 weeks and birth weight less than 2500 g bull hemolysis due to maternal isoimmunization G6PD deficiency spherocytosis or other causes bull jaundice at less than 24 h of age bull sepsis and bull the need for resuscitation at birth
Jaundice in the Healthy Term Newborn
April 2002 Page 14 of 20
Clinical management of hyperbilirubinemia in infants
A bilirubin level that justifies consideration of phototherapy should mandate the investigation of the cause ofhyperbilirubinemia Investigation should include a clinically pertinent history of the mother family historydescription of labour and delivery and infantrsquos clinical course (26) A physical examination should besupplemented by laboratory investigations (Table 1) including determination of unconjugated and conjugatedserum bilirubin concentrations and blood group with direct antibody test (Coombsrsquo test) and hemoglobin andhematocrit levels A complete blood count including differential white cell count and a blood smear for red cellmorphology may be indicated Further tests (eg reticulocyte count G6PD screen) may be indicated based oninitial results ethnicity or clinical presentation Testing for serum electrolytes and albumin or protein areindicated in some situations such as suspected dehydration or when bilirubin levels approach exchange valuesIn the absence of drugs or clinical states that alter the binding of bilirubin by albumin the bilirubin to albuminor the bilirubin to protein ratio reflects the free bilirubin concentration and the binding capacity of the serum(27-29) At a bilirubin concentration close to exchange transfusion levels some clinicians may wish to ensurethat serum bilirubin binding is normal (albumin 25 gL or greater protein 54 gL or greater) Values belowthese levels may be associated with low bilirubin binding and may be used by the clinician when decidingwhether further intervention (eg exchange transfusion) should take place (27)
TABLE 1 Laboratory investigation for hyperbilirubinemia in term newborn infants
Indicated (if bilirubin concentrations reach phototherapy levels) Serum total or unconjugated bilirubin concentration Serum conjugated bilirubin concentration Blood group with direct antibody test (Coombsrsquo test) Hemoglobin and hematocrit determinations
Optional (in specific clinical circumstances) Complete blood count including manual differential white cell count Blood smear for red cell morphology Reticulocyte count Glucose-6-phosphate dehydrogenase screen Serum electrolytes and albumin or protein concentrations
For infants with prolonged jaundice (lasting longer than seven days) or with conjugated hyperbilirubinemia(greater than 30 micromolL) additional investigation and management may be required and a consultation with aspecialist may be needed (30)
During the past decade most nurseries have shortened the time of hospital stay for term healthy newborninfants Early discharge of neonates means that jaundice is not often recognized at discharge (31) The CanadianPaediatric Society reiterates the importance of allowing early discharge only if a healthy status is confirmed foreach baby and appropriate follow-up is provided (32) Appropriate parental education about feeding signs ofdehydration and jaundice must be implemented in hospital nurseries Testing for serum bilirubin concentrationsmust be readily available for newborns on an out-patient basis Readmission to hospital (usually the hospital ofbirth) may be necessary for the investigation and management of hyperbilirubinemia
Exchange transfusion If phototherapy fails to control the rising bilirubin levels exchange transfusion is indicated to lower serumbilirubin concentrations For healthy term infants without risk factors exchange transfusion should beconsidered at serum unconjugated bilirubin concentrations of 400 to 430 micromolL For term infants with riskfactors the level should be 340 micromolL For infants who initially present with serum bilirubin concentrations in
Jaundice in the Healthy Term Newborn
April 2002 Page 15 of 20
excess of exchange levels intensive phototherapy should produce a decline of serum unconjugated bilirubinfrom 20 to 35 micromolL within 4 to 6 h and levels should continue to fall thereafter and remain below thethreshold for exchange transfusion If the bilirubin concentration does not decrease after adequate rehydrationand 4 to 6 h of intensive phototherapy exchange transfusion should be considered Preparation for thisincluding ensuring availability of blood should occur shortly after the admission of babies whose bilirubinconcentrations exceed exchange levels Appropriate consultation should be obtained if the etiology ofhyperbilirubinemia is unclear the infant is ill and particularly if bilirubin concentrations are approachingexchange levels Because the risks of exchange transfusion are significant the best management may bereviewed with an expert opinion from a neonatologist
Conclusions Hyperbilirubinemia in apparently healthy term newborn infants continues to hold the potential threat ofcomplications from bilirubin encephalopathy and kernicterus Careful assessment of risk factors judicious useof phototherapy appropriate laboratory monitoring and specific treatment of other disorders (eg sepsis) areessential for the optimal management of hyperbilirubinemia Appropriate laboratory facilities must be availableto measure bilirubin concentrations for out-patients in required clinical situations Readmission to hospital maybe required if phototherapy is necessary Guidelines for phototherapy are presented for term babies with andwithout identifiable risk factors
References
1 Fetus and Newborn Committee Canadian Paediatric Society Use of phototherapy for neonatalhyperbilirubinemia Can Med Assoc J 19861341237-45 2 American Academy of Pediatrics Practice parameter Management of hyperbilirubinemia in the healthy termnewborn Pediatrics 199494558-65 3 Hansen TWR Therapeutical approaches to neonatal jaundice an international survey Clin Pediatr199635309-16 4 Valaes T Koliopoulos C Koltsidopoulos A The impact of phototherapy in the management of neonatalhyperbilirubinemia comparison of historical cohorts Acta Paediatrica 199685273-6 5 Gustafson PA Boyle DW Bilirubin index a new standard for intervention Med Hypotheses 199545409-16 6 Torres-Torres M Tayaba R Weintraub A Holzman IR New perspectives on neonatal hyperbilirubinemiaMount Sinai J Med 199461424-8 7 Lazar L Litwin A Merlob P Phototherapy for neonatal nonhemolytic hyperbilirubinemia analysis ofrebound and indications for discontinuing therapy Clin Pediatr 199332264-7 8 Newman TB Maisels MJ Evaluation and treatment of jaundice in the term newborn Pediatrics 199289809-18 9 McMillan DD Lockyer JM Magnan L Akierman A Parboosingh JT Effect of educational program andinterview on adoption of guidelines for the management of neonatal hyperbilirubinemia Can Med Assoc J1991144707-12 10 Brown AK Johnson L Loss of concern about jaundice and the reemergence of kernicterus in full-terminfants in the era of managed care In Fanaroff AA Klaus MH eds The Year Book of Neonatal and PerinatalMedicine Philadelphia Mosby Yearbook 199617-28 11 Valaes T Bilirubin toxicity The problem was solved a generation ago Pediatrics 199289819-21 12 Wennberg RP Bilirubin recommendations present problems New guidelines simplistic and untestedPediatrics 199289821-2 13 Merenstein GB lsquoNewrsquo bilirubin recommendations questioned Pediatrics 199289822-3 14 Poland RL In search of a lsquogold standardrsquo for bilirubin toxicity Pediatrics 199289823-4 15 Brown AK Seidman DS Stevenson DK Jaundice in healthy term neonates Do we need new action levelsor new approaches Pediatrics 199289827-9 16 Johnson L Yet another expert opinion on bilirubin toxicity Pediatrics 199289829-31
Jaundice in the Healthy Term Newborn
April 2002 Page 16 of 20
17 MacDonald MG Hidden risks Early discharge and bilirubin toxicity due to glucose-6-phosphatedehydrogenase deficiency Pediatrics 199596734-8 18 Maisels MJ Newman TB Kernicterus in otherwise healthy breast-fed newborns Pediatrics 199596730-3 19 Vogl TP Phototherapy of neonatal hyperbilirubinemia bilirubin in unexposed areas of the skin J Pediatr197485707-1020 Rubaltelli FF Carli M The effect of light on cutaneous bilirubin Biol Neonate 197118457-62 21 Sisson TR Kendall N Shaw E et al Phototherapy of jaundice in the newborn infant 2 Effect of variouslight intensities J Pediatr 19738135-8 22 Bonta BW Warshaw JB Importance of radiant flux in the treatment of hyperbilirubinemia failure ofoverhead phototherapy units in intensive care units Pediatrics 197657502-5 23 Warshaw JB Gagliardi J Patel A A comparison of fluorescent and non-fluorescent light source forphototherapy Pediatrics 198065795-8 24 Ennever JF Blue light green light white light more light treatment of neonatal jaundice Clin Perinatol199017467-8125 Auerbach KG Gartner LM Breastfeeding and human milk their association with jaundice in the neonateClin Perinatol 19871489-108 26 Maisels MJ Jaundice in the newborn Pediatr Rev 19823305-20 27 Ahlfors CE Criteria for exchange transfusion in jaundiced newborns Pediatrics 199493488-94 28 Odell GB Storey GNB Rosenberg LA Studies in kernicterus III The saturation of serum protein withbilirubin during neonatal life and its relationship to brain damage at 5 years J Pediatr 19707612-21 29 Wirth FH Goldberg KE Lubchenco LO The neurologic outcome of infants evaluated for unboundbilirubin Pediatr Res 19759385-91 30 Haber BA Lake AM Cholestatic jaundice in the newborn Clin Perinatol 199017483-506 31 Maisels MJ Newman TB Jaundice in full-term and near-term babies who leave the hospital within 36hours The pediatricianrsquos nemesis Clin Perinatol 199825295-302 32 Fetus and Newborn Committee Canadian Paediatric Society and Society of Obstetricians andGynaecologists of Canada Facilitating discharge home following a normal term birth Paediatr Child Health19961165-8
Fetus and Newborn Committee Members Drs John Watts Department of Paediatrics Childrenrsquos Hospital ndash Hamilton Health Sciences CentreHamilton Ontario (director responsible) Douglas McMillan Department of Pediatrics Foothills HospitalCalgary Alberta (chair) Arne Ohlsson Department of Paediatrics Mount Sinai Hospital Toronto Ontario(co-chair) Deborah Davis Childrenrsquos Hospital of Eastern Ontario Ottawa Ontario Daniel Faucher RoyalVictoria Hospital Montreal Quebec (principal author) John Van Aerde Stollery Childrenrsquos Health CentreEdmonton Alberta Michael Vincer IWK-Grace Health Centre Halifax Nova ScotiaConsultant Dr Michael C Klein University of British Columbia Vancouver British Columbia (College ofFamily Physicians of Canada)Liaisons Drs James Lemon Riley Childrenrsquos Hospital Indiana University Medical Center IndianapolisIndiana (American Academy of Pediatrics) Saroj Saigal Department of Paediatrics McMaster UniversityMedical Centre Childrenrsquos Hospital ndash Hamilton Health Sciences Centre Hamilton Ontario (CPS Neonatal-Perinatal Medicine Section) Cheryl Levitt Department of Family Medicine Childrenrsquos Hospital ndash HamiltonHealth Sciences Centre Hamilton Ontario (College of Family Physicians of Canada) Catherine McCourtDirector Bureau of Reproductive amp Child Health Laboratory Centre for Disease Control Ottawa Ontario(Health Canada) Mrs Debbie Fraser-Askin Winnipeg Manitoba (Neonatal Nurses) Dr Line LeducDepartment of Obstetrics-Gynecology Hocircpital Sainte-Justine Montreal Quebec (Society of Obstetricians andGynaecologists of Canada)
Disclaimer The recommendations in this position statement do not indicate an exclusive course oftreatment or procedure to be followed Variations taking into account individual circumstances may beappropriate
Jaundice in the Healthy Term Newborn
April 2002 Page 17 of 20
APPENDIX 3Hyperbilirubinemia Risk Designation for Term and Near-Term Well Newborns
Jaundice in the Healthy Term Newborn
April 2002 Page 18 of 20
APPENDIX 4
American Academy of Pediatrics 1994 Practice parameter Management ofHyperbilirubinemia in the Healthy Term Newborn Pediatrics 94(4) 558-565
(Chart and Algorithm)
Jaundice in the Healthy Term Newborn
April 2002 Page 19 of 20
AlgorithmPediatric clinician evaluatesterm newborn with jaundice
Does the infant have signs of underlyingserious illness (lethargy apnea tachypneatemperature instability behavior changeshepatosplenomegaly persistant vomiting
or persistent feeding difficulty)
1
2
Exit this algorithm to individualizedclinical evaluation including
assessment of jaundice and underlyingdisease
Yes
3
No
Is the infant lt 37 weeks gestational age
4 Exit this algorithm to individualizedclinical evaluation including
assessment of jaundice in light ofprematurity
5
Yes
Is the mothersABO and Rh
blood typing andisoimmune
antibody screenstatus known
Is the mothersblood Rhpositive
Does themothers blood
have anyimmune
antibodies
Consider holding the infantscord blood in the blood bank incase future testing is necessary
6 7 8 9No
Yes Yes No
(Go to Box 10) (Go to Box 10) (Go to Box 10) (Go to Box 13)
No No Yes
Perform blood typing (ABO and Rh) and direct Coombs testingon the infants cord (preferably) or venous blood
10
Is the infantsblood direct
Coombs testpositive
Exit this algorithm to individualized clinical evaluationincluding assessment of jaundice and isoimmune
hemolytic disease
11 12
Yes
Are any of the following risk factors present tosuggest that nonisoimmune hemolytic disease
is possible in this infant(1) Family history of hemolytic anemia
OR(2) Family history of early or severe jaundice
OR(3) Ethnicity or geographic originassociated with hemolytic anemia
OR(4) Early or severe jaundice
Perform appropriate laboratoryassessment of infant including
(but not limited to consideration of)(1) Complete blood count differentialsmear reticulocyte count(2) G6PD screen(3) Hemoglobin electrophoresis
1314
No
No
No
(Go to Box 16)
Does the evaluation suggesthemolytic disease
15
Yes
(Go to Box 17)(Go to Box 16)
No
Jaundice in the Healthy Term Newborn
April 2002 Page 20 of 20
AlgorithmIs the infant
jaundiced andlt 24 hours of
age
Exit this algorithm to individualizedclinical evaluation includingassessment of jaundice and
nonisoimmune hemolytic disease
Is jaundiceclinicallysignificant by medical
judgment
(1) Measure infantstotal serum bilirubin(2) Go to Box 27
Healthy term infant with jaundice not clinicallysignificant by medical judgment
Follow infant in routine clinical supervision
1617
18 19
20
21
(Go to Box 22)
Yes
Yes
No
No
Is jaundicepersisting
gt 2 weeks
Does this infant haveabnormal physicalexam results dark
urine or light stools
Is jaundice persistinggt 3 weeks
Perform appropriate physical andlaboratory assessment of theinfant including possibility of
cholestatic jaundice
Provide routine carerecommend routine
feeding and follow-up Table 2 Management of Hyperbilirubinemia in the Healthy Term NewbornAgehours TSB Level mgdL (umolL)
Consider Phototherapy Exchange ExchangePhototherapy Transfusion Transfusion
if Intensive and IntensivePhototherapy PhototherapyFails
lt24 25-48 gt 12 (170) gt15 (260) gt 20 (340) gt 25 (430)49-72 gt 15 (260) gt 18 (310) gt 25 (430) gt 30 (510)gt 72 gt 17 (290) gt 20 (340) gt 25 (430) gt 30 (510)
TSB indicates total serum bilirubinPhototherapy at these TSB levels is a clinical option meaning that the intervention is availableand may be used on the basis of individual clinical judgement For a more detailed descriptionof phototherapy see the AppendixIntensive phototherapy (Appendix) should produce a decline of TSB of 1 to 2 mgdL within 4 to 6hours and the TSB level should continue to fall and remain below the threshold level for exchangetransfusion If this does not occur it is considered a failure of phototherapyTerm infants who are clinically jaundiced at lt 24 hours old are not considered healthy andrequire further evaluation (see text)
22 23
24
25
26
YesYes
No
YesNo
No 27
Algorithm Management of hyperbilirubinemia inthe healthy term infant
(From Box 19)
Jaundice in the Healthy Term Newborn
April 2002 Page 12 of 20
Until recently these strategies suggested maintaining serum unconjugated bilirubin concentrations below 340micromolL (20 mgdL) in healthy term infants through the use of phototherapy or exchange transfusion (11) Whileexchange transfusions had been a frequent occurrence from the 1950s to the 1970s and may sometimes still berequired phototherapy has become the mainstay of medical management of hyperbilirubinemia since that time
The cases of kernicterus originally described occurred mainly in infants with hemolytic disease Higher serumunconjugated bilirubin concentrations may be safe in healthy term infants without hemolytic disease It is notpossible to predict at what level an individual infant may develop kernicterus
Several authors have expressed serious concerns over the approach of allowing higher serum unconjugatedbilirubin concentrations to occur before investigating and treating these term infants (11-16) Brown andJohnson (10) have reported 23 cases of kernicterus occurring since 1989 16 in term and seven in near terminfants In these infants peak unconjugated bilirubin concentrations of 375 to 860 micromolL (22 to 50 mgdL)were seen All but one infant was breastfed Other associations found in these infants with kernicterus weredehydration (seven infants) glucose-6-phosphate dehydrogenase (G6PD) deficiency (five infants) ABOalloimmunization (one infant) hemolysis of unknown cause (five infants) familial etiology (one infant) andotherwise unexplained early jaundice clinically evident before 24 h of age (six infants) Similar cases have beenreported by others (1718) Although many of these babies were subsequently found to have additional riskfactors these factors were not often identified at the time the baby was noted to be jaundiced
Since the introduction in the 1990s of the kinder gentler approach to the management of hyperbilirubinemia agreat deal of confusion has arisen about approaches to the management of hyperbilirubinemia in healthy terminfants This confusion has extended to the care of borderline preterm infants who have often been treated asterm infants A recently published international survey reported considerable variability in the approach tohyperbilirubinemia and the use of phototherapy among neonatal units worldwide (3)
PhototherapyThe goal of hyperbilirubinemia treatment is to avoid bilirubin concentrations that may result in kernicterusPhototherapy remains an effective therapeutic intervention that decreases bilirubin concentrations therebypreventing elevated bilirubin levels associated with permanent sequelae
The effectiveness of phototherapy is related to the area of skin exposed and the radiant energy and thewavelength of the light (19-23) Phototherapy acts on unconjugated bilirubin to a depth of 2 mm from theepidermis Phototherapy changes the bilirubin through structural photoisomerization into water-solublelumirubin that is excreted in the urine (19) The fall in bilirubin level is proportionately greater in the skin thanin the serum (20) Therefore the infant receiving phototherapy should have as much skin as possible exposed tothe lights More intense phototherapy may be achieved by using multiple sources of phototherapy double ortriple phototherapy is recommended to optimize the skin surface exposed and therefore the efficacy ofphototherapy More detailed discussion of the physics of phototherapy has been published (124) It is important to recognize the relationship between dehydration and hyperbilirubinemia Dehydration may beassociated with increased serum bilirubin concentrations and may be exacerbated by phototherapy Alljaundiced infants should be adequately hydrated before and during phototherapy Breastfeeding is notcontraindicated in the presence of hyperbilirubinemia and should be continued More frequent breastfeedingsmay be beneficial (25)
The concentrations of bilirubin at which phototherapy might be initiated in healthy term infants and those withrisk factors are shown in Figure 1 Guidelines for phototherapy in low birth weight infants remain as previouslypublished (1) The bilirubin concentrations at which phototherapy is suggested by the Canadian PaediatricSociety in the present statement are more conservative than the current recommendations of the AmericanAcademy of Pediatrics (2) If the infant is a healthy term newborn phototherapy should be started as indicated
Jaundice in the Healthy Term Newborn
April 2002 Page 13 of 20
in the upper curve of Figure 1 If the infant has one or more risk factors a clinical decision should be made toinitiate phototherapy at the concentration indicated by the lower curve
Figure 1 Guidelines for initiation of phototherapy for hyperbilirubinemia in term infants with and without riskfactors Some risk factors include gestional age younger than 37 weeks birth weight less than 2500 ghemolysis jaundice at younger than 24 h of age sepsis and the need for resuscitation at birth
The timely recognition of risk factors is essential to minimize the danger of kernicterus The risk factors are asfollows
bull gestational age younger than 37 weeks and birth weight less than 2500 g bull hemolysis due to maternal isoimmunization G6PD deficiency spherocytosis or other causes bull jaundice at less than 24 h of age bull sepsis and bull the need for resuscitation at birth
Jaundice in the Healthy Term Newborn
April 2002 Page 14 of 20
Clinical management of hyperbilirubinemia in infants
A bilirubin level that justifies consideration of phototherapy should mandate the investigation of the cause ofhyperbilirubinemia Investigation should include a clinically pertinent history of the mother family historydescription of labour and delivery and infantrsquos clinical course (26) A physical examination should besupplemented by laboratory investigations (Table 1) including determination of unconjugated and conjugatedserum bilirubin concentrations and blood group with direct antibody test (Coombsrsquo test) and hemoglobin andhematocrit levels A complete blood count including differential white cell count and a blood smear for red cellmorphology may be indicated Further tests (eg reticulocyte count G6PD screen) may be indicated based oninitial results ethnicity or clinical presentation Testing for serum electrolytes and albumin or protein areindicated in some situations such as suspected dehydration or when bilirubin levels approach exchange valuesIn the absence of drugs or clinical states that alter the binding of bilirubin by albumin the bilirubin to albuminor the bilirubin to protein ratio reflects the free bilirubin concentration and the binding capacity of the serum(27-29) At a bilirubin concentration close to exchange transfusion levels some clinicians may wish to ensurethat serum bilirubin binding is normal (albumin 25 gL or greater protein 54 gL or greater) Values belowthese levels may be associated with low bilirubin binding and may be used by the clinician when decidingwhether further intervention (eg exchange transfusion) should take place (27)
TABLE 1 Laboratory investigation for hyperbilirubinemia in term newborn infants
Indicated (if bilirubin concentrations reach phototherapy levels) Serum total or unconjugated bilirubin concentration Serum conjugated bilirubin concentration Blood group with direct antibody test (Coombsrsquo test) Hemoglobin and hematocrit determinations
Optional (in specific clinical circumstances) Complete blood count including manual differential white cell count Blood smear for red cell morphology Reticulocyte count Glucose-6-phosphate dehydrogenase screen Serum electrolytes and albumin or protein concentrations
For infants with prolonged jaundice (lasting longer than seven days) or with conjugated hyperbilirubinemia(greater than 30 micromolL) additional investigation and management may be required and a consultation with aspecialist may be needed (30)
During the past decade most nurseries have shortened the time of hospital stay for term healthy newborninfants Early discharge of neonates means that jaundice is not often recognized at discharge (31) The CanadianPaediatric Society reiterates the importance of allowing early discharge only if a healthy status is confirmed foreach baby and appropriate follow-up is provided (32) Appropriate parental education about feeding signs ofdehydration and jaundice must be implemented in hospital nurseries Testing for serum bilirubin concentrationsmust be readily available for newborns on an out-patient basis Readmission to hospital (usually the hospital ofbirth) may be necessary for the investigation and management of hyperbilirubinemia
Exchange transfusion If phototherapy fails to control the rising bilirubin levels exchange transfusion is indicated to lower serumbilirubin concentrations For healthy term infants without risk factors exchange transfusion should beconsidered at serum unconjugated bilirubin concentrations of 400 to 430 micromolL For term infants with riskfactors the level should be 340 micromolL For infants who initially present with serum bilirubin concentrations in
Jaundice in the Healthy Term Newborn
April 2002 Page 15 of 20
excess of exchange levels intensive phototherapy should produce a decline of serum unconjugated bilirubinfrom 20 to 35 micromolL within 4 to 6 h and levels should continue to fall thereafter and remain below thethreshold for exchange transfusion If the bilirubin concentration does not decrease after adequate rehydrationand 4 to 6 h of intensive phototherapy exchange transfusion should be considered Preparation for thisincluding ensuring availability of blood should occur shortly after the admission of babies whose bilirubinconcentrations exceed exchange levels Appropriate consultation should be obtained if the etiology ofhyperbilirubinemia is unclear the infant is ill and particularly if bilirubin concentrations are approachingexchange levels Because the risks of exchange transfusion are significant the best management may bereviewed with an expert opinion from a neonatologist
Conclusions Hyperbilirubinemia in apparently healthy term newborn infants continues to hold the potential threat ofcomplications from bilirubin encephalopathy and kernicterus Careful assessment of risk factors judicious useof phototherapy appropriate laboratory monitoring and specific treatment of other disorders (eg sepsis) areessential for the optimal management of hyperbilirubinemia Appropriate laboratory facilities must be availableto measure bilirubin concentrations for out-patients in required clinical situations Readmission to hospital maybe required if phototherapy is necessary Guidelines for phototherapy are presented for term babies with andwithout identifiable risk factors
References
1 Fetus and Newborn Committee Canadian Paediatric Society Use of phototherapy for neonatalhyperbilirubinemia Can Med Assoc J 19861341237-45 2 American Academy of Pediatrics Practice parameter Management of hyperbilirubinemia in the healthy termnewborn Pediatrics 199494558-65 3 Hansen TWR Therapeutical approaches to neonatal jaundice an international survey Clin Pediatr199635309-16 4 Valaes T Koliopoulos C Koltsidopoulos A The impact of phototherapy in the management of neonatalhyperbilirubinemia comparison of historical cohorts Acta Paediatrica 199685273-6 5 Gustafson PA Boyle DW Bilirubin index a new standard for intervention Med Hypotheses 199545409-16 6 Torres-Torres M Tayaba R Weintraub A Holzman IR New perspectives on neonatal hyperbilirubinemiaMount Sinai J Med 199461424-8 7 Lazar L Litwin A Merlob P Phototherapy for neonatal nonhemolytic hyperbilirubinemia analysis ofrebound and indications for discontinuing therapy Clin Pediatr 199332264-7 8 Newman TB Maisels MJ Evaluation and treatment of jaundice in the term newborn Pediatrics 199289809-18 9 McMillan DD Lockyer JM Magnan L Akierman A Parboosingh JT Effect of educational program andinterview on adoption of guidelines for the management of neonatal hyperbilirubinemia Can Med Assoc J1991144707-12 10 Brown AK Johnson L Loss of concern about jaundice and the reemergence of kernicterus in full-terminfants in the era of managed care In Fanaroff AA Klaus MH eds The Year Book of Neonatal and PerinatalMedicine Philadelphia Mosby Yearbook 199617-28 11 Valaes T Bilirubin toxicity The problem was solved a generation ago Pediatrics 199289819-21 12 Wennberg RP Bilirubin recommendations present problems New guidelines simplistic and untestedPediatrics 199289821-2 13 Merenstein GB lsquoNewrsquo bilirubin recommendations questioned Pediatrics 199289822-3 14 Poland RL In search of a lsquogold standardrsquo for bilirubin toxicity Pediatrics 199289823-4 15 Brown AK Seidman DS Stevenson DK Jaundice in healthy term neonates Do we need new action levelsor new approaches Pediatrics 199289827-9 16 Johnson L Yet another expert opinion on bilirubin toxicity Pediatrics 199289829-31
Jaundice in the Healthy Term Newborn
April 2002 Page 16 of 20
17 MacDonald MG Hidden risks Early discharge and bilirubin toxicity due to glucose-6-phosphatedehydrogenase deficiency Pediatrics 199596734-8 18 Maisels MJ Newman TB Kernicterus in otherwise healthy breast-fed newborns Pediatrics 199596730-3 19 Vogl TP Phototherapy of neonatal hyperbilirubinemia bilirubin in unexposed areas of the skin J Pediatr197485707-1020 Rubaltelli FF Carli M The effect of light on cutaneous bilirubin Biol Neonate 197118457-62 21 Sisson TR Kendall N Shaw E et al Phototherapy of jaundice in the newborn infant 2 Effect of variouslight intensities J Pediatr 19738135-8 22 Bonta BW Warshaw JB Importance of radiant flux in the treatment of hyperbilirubinemia failure ofoverhead phototherapy units in intensive care units Pediatrics 197657502-5 23 Warshaw JB Gagliardi J Patel A A comparison of fluorescent and non-fluorescent light source forphototherapy Pediatrics 198065795-8 24 Ennever JF Blue light green light white light more light treatment of neonatal jaundice Clin Perinatol199017467-8125 Auerbach KG Gartner LM Breastfeeding and human milk their association with jaundice in the neonateClin Perinatol 19871489-108 26 Maisels MJ Jaundice in the newborn Pediatr Rev 19823305-20 27 Ahlfors CE Criteria for exchange transfusion in jaundiced newborns Pediatrics 199493488-94 28 Odell GB Storey GNB Rosenberg LA Studies in kernicterus III The saturation of serum protein withbilirubin during neonatal life and its relationship to brain damage at 5 years J Pediatr 19707612-21 29 Wirth FH Goldberg KE Lubchenco LO The neurologic outcome of infants evaluated for unboundbilirubin Pediatr Res 19759385-91 30 Haber BA Lake AM Cholestatic jaundice in the newborn Clin Perinatol 199017483-506 31 Maisels MJ Newman TB Jaundice in full-term and near-term babies who leave the hospital within 36hours The pediatricianrsquos nemesis Clin Perinatol 199825295-302 32 Fetus and Newborn Committee Canadian Paediatric Society and Society of Obstetricians andGynaecologists of Canada Facilitating discharge home following a normal term birth Paediatr Child Health19961165-8
Fetus and Newborn Committee Members Drs John Watts Department of Paediatrics Childrenrsquos Hospital ndash Hamilton Health Sciences CentreHamilton Ontario (director responsible) Douglas McMillan Department of Pediatrics Foothills HospitalCalgary Alberta (chair) Arne Ohlsson Department of Paediatrics Mount Sinai Hospital Toronto Ontario(co-chair) Deborah Davis Childrenrsquos Hospital of Eastern Ontario Ottawa Ontario Daniel Faucher RoyalVictoria Hospital Montreal Quebec (principal author) John Van Aerde Stollery Childrenrsquos Health CentreEdmonton Alberta Michael Vincer IWK-Grace Health Centre Halifax Nova ScotiaConsultant Dr Michael C Klein University of British Columbia Vancouver British Columbia (College ofFamily Physicians of Canada)Liaisons Drs James Lemon Riley Childrenrsquos Hospital Indiana University Medical Center IndianapolisIndiana (American Academy of Pediatrics) Saroj Saigal Department of Paediatrics McMaster UniversityMedical Centre Childrenrsquos Hospital ndash Hamilton Health Sciences Centre Hamilton Ontario (CPS Neonatal-Perinatal Medicine Section) Cheryl Levitt Department of Family Medicine Childrenrsquos Hospital ndash HamiltonHealth Sciences Centre Hamilton Ontario (College of Family Physicians of Canada) Catherine McCourtDirector Bureau of Reproductive amp Child Health Laboratory Centre for Disease Control Ottawa Ontario(Health Canada) Mrs Debbie Fraser-Askin Winnipeg Manitoba (Neonatal Nurses) Dr Line LeducDepartment of Obstetrics-Gynecology Hocircpital Sainte-Justine Montreal Quebec (Society of Obstetricians andGynaecologists of Canada)
Disclaimer The recommendations in this position statement do not indicate an exclusive course oftreatment or procedure to be followed Variations taking into account individual circumstances may beappropriate
Jaundice in the Healthy Term Newborn
April 2002 Page 17 of 20
APPENDIX 3Hyperbilirubinemia Risk Designation for Term and Near-Term Well Newborns
Jaundice in the Healthy Term Newborn
April 2002 Page 18 of 20
APPENDIX 4
American Academy of Pediatrics 1994 Practice parameter Management ofHyperbilirubinemia in the Healthy Term Newborn Pediatrics 94(4) 558-565
(Chart and Algorithm)
Jaundice in the Healthy Term Newborn
April 2002 Page 19 of 20
AlgorithmPediatric clinician evaluatesterm newborn with jaundice
Does the infant have signs of underlyingserious illness (lethargy apnea tachypneatemperature instability behavior changeshepatosplenomegaly persistant vomiting
or persistent feeding difficulty)
1
2
Exit this algorithm to individualizedclinical evaluation including
assessment of jaundice and underlyingdisease
Yes
3
No
Is the infant lt 37 weeks gestational age
4 Exit this algorithm to individualizedclinical evaluation including
assessment of jaundice in light ofprematurity
5
Yes
Is the mothersABO and Rh
blood typing andisoimmune
antibody screenstatus known
Is the mothersblood Rhpositive
Does themothers blood
have anyimmune
antibodies
Consider holding the infantscord blood in the blood bank incase future testing is necessary
6 7 8 9No
Yes Yes No
(Go to Box 10) (Go to Box 10) (Go to Box 10) (Go to Box 13)
No No Yes
Perform blood typing (ABO and Rh) and direct Coombs testingon the infants cord (preferably) or venous blood
10
Is the infantsblood direct
Coombs testpositive
Exit this algorithm to individualized clinical evaluationincluding assessment of jaundice and isoimmune
hemolytic disease
11 12
Yes
Are any of the following risk factors present tosuggest that nonisoimmune hemolytic disease
is possible in this infant(1) Family history of hemolytic anemia
OR(2) Family history of early or severe jaundice
OR(3) Ethnicity or geographic originassociated with hemolytic anemia
OR(4) Early or severe jaundice
Perform appropriate laboratoryassessment of infant including
(but not limited to consideration of)(1) Complete blood count differentialsmear reticulocyte count(2) G6PD screen(3) Hemoglobin electrophoresis
1314
No
No
No
(Go to Box 16)
Does the evaluation suggesthemolytic disease
15
Yes
(Go to Box 17)(Go to Box 16)
No
Jaundice in the Healthy Term Newborn
April 2002 Page 20 of 20
AlgorithmIs the infant
jaundiced andlt 24 hours of
age
Exit this algorithm to individualizedclinical evaluation includingassessment of jaundice and
nonisoimmune hemolytic disease
Is jaundiceclinicallysignificant by medical
judgment
(1) Measure infantstotal serum bilirubin(2) Go to Box 27
Healthy term infant with jaundice not clinicallysignificant by medical judgment
Follow infant in routine clinical supervision
1617
18 19
20
21
(Go to Box 22)
Yes
Yes
No
No
Is jaundicepersisting
gt 2 weeks
Does this infant haveabnormal physicalexam results dark
urine or light stools
Is jaundice persistinggt 3 weeks
Perform appropriate physical andlaboratory assessment of theinfant including possibility of
cholestatic jaundice
Provide routine carerecommend routine
feeding and follow-up Table 2 Management of Hyperbilirubinemia in the Healthy Term NewbornAgehours TSB Level mgdL (umolL)
Consider Phototherapy Exchange ExchangePhototherapy Transfusion Transfusion
if Intensive and IntensivePhototherapy PhototherapyFails
lt24 25-48 gt 12 (170) gt15 (260) gt 20 (340) gt 25 (430)49-72 gt 15 (260) gt 18 (310) gt 25 (430) gt 30 (510)gt 72 gt 17 (290) gt 20 (340) gt 25 (430) gt 30 (510)
TSB indicates total serum bilirubinPhototherapy at these TSB levels is a clinical option meaning that the intervention is availableand may be used on the basis of individual clinical judgement For a more detailed descriptionof phototherapy see the AppendixIntensive phototherapy (Appendix) should produce a decline of TSB of 1 to 2 mgdL within 4 to 6hours and the TSB level should continue to fall and remain below the threshold level for exchangetransfusion If this does not occur it is considered a failure of phototherapyTerm infants who are clinically jaundiced at lt 24 hours old are not considered healthy andrequire further evaluation (see text)
22 23
24
25
26
YesYes
No
YesNo
No 27
Algorithm Management of hyperbilirubinemia inthe healthy term infant
(From Box 19)
Jaundice in the Healthy Term Newborn
April 2002 Page 13 of 20
in the upper curve of Figure 1 If the infant has one or more risk factors a clinical decision should be made toinitiate phototherapy at the concentration indicated by the lower curve
Figure 1 Guidelines for initiation of phototherapy for hyperbilirubinemia in term infants with and without riskfactors Some risk factors include gestional age younger than 37 weeks birth weight less than 2500 ghemolysis jaundice at younger than 24 h of age sepsis and the need for resuscitation at birth
The timely recognition of risk factors is essential to minimize the danger of kernicterus The risk factors are asfollows
bull gestational age younger than 37 weeks and birth weight less than 2500 g bull hemolysis due to maternal isoimmunization G6PD deficiency spherocytosis or other causes bull jaundice at less than 24 h of age bull sepsis and bull the need for resuscitation at birth
Jaundice in the Healthy Term Newborn
April 2002 Page 14 of 20
Clinical management of hyperbilirubinemia in infants
A bilirubin level that justifies consideration of phototherapy should mandate the investigation of the cause ofhyperbilirubinemia Investigation should include a clinically pertinent history of the mother family historydescription of labour and delivery and infantrsquos clinical course (26) A physical examination should besupplemented by laboratory investigations (Table 1) including determination of unconjugated and conjugatedserum bilirubin concentrations and blood group with direct antibody test (Coombsrsquo test) and hemoglobin andhematocrit levels A complete blood count including differential white cell count and a blood smear for red cellmorphology may be indicated Further tests (eg reticulocyte count G6PD screen) may be indicated based oninitial results ethnicity or clinical presentation Testing for serum electrolytes and albumin or protein areindicated in some situations such as suspected dehydration or when bilirubin levels approach exchange valuesIn the absence of drugs or clinical states that alter the binding of bilirubin by albumin the bilirubin to albuminor the bilirubin to protein ratio reflects the free bilirubin concentration and the binding capacity of the serum(27-29) At a bilirubin concentration close to exchange transfusion levels some clinicians may wish to ensurethat serum bilirubin binding is normal (albumin 25 gL or greater protein 54 gL or greater) Values belowthese levels may be associated with low bilirubin binding and may be used by the clinician when decidingwhether further intervention (eg exchange transfusion) should take place (27)
TABLE 1 Laboratory investigation for hyperbilirubinemia in term newborn infants
Indicated (if bilirubin concentrations reach phototherapy levels) Serum total or unconjugated bilirubin concentration Serum conjugated bilirubin concentration Blood group with direct antibody test (Coombsrsquo test) Hemoglobin and hematocrit determinations
Optional (in specific clinical circumstances) Complete blood count including manual differential white cell count Blood smear for red cell morphology Reticulocyte count Glucose-6-phosphate dehydrogenase screen Serum electrolytes and albumin or protein concentrations
For infants with prolonged jaundice (lasting longer than seven days) or with conjugated hyperbilirubinemia(greater than 30 micromolL) additional investigation and management may be required and a consultation with aspecialist may be needed (30)
During the past decade most nurseries have shortened the time of hospital stay for term healthy newborninfants Early discharge of neonates means that jaundice is not often recognized at discharge (31) The CanadianPaediatric Society reiterates the importance of allowing early discharge only if a healthy status is confirmed foreach baby and appropriate follow-up is provided (32) Appropriate parental education about feeding signs ofdehydration and jaundice must be implemented in hospital nurseries Testing for serum bilirubin concentrationsmust be readily available for newborns on an out-patient basis Readmission to hospital (usually the hospital ofbirth) may be necessary for the investigation and management of hyperbilirubinemia
Exchange transfusion If phototherapy fails to control the rising bilirubin levels exchange transfusion is indicated to lower serumbilirubin concentrations For healthy term infants without risk factors exchange transfusion should beconsidered at serum unconjugated bilirubin concentrations of 400 to 430 micromolL For term infants with riskfactors the level should be 340 micromolL For infants who initially present with serum bilirubin concentrations in
Jaundice in the Healthy Term Newborn
April 2002 Page 15 of 20
excess of exchange levels intensive phototherapy should produce a decline of serum unconjugated bilirubinfrom 20 to 35 micromolL within 4 to 6 h and levels should continue to fall thereafter and remain below thethreshold for exchange transfusion If the bilirubin concentration does not decrease after adequate rehydrationand 4 to 6 h of intensive phototherapy exchange transfusion should be considered Preparation for thisincluding ensuring availability of blood should occur shortly after the admission of babies whose bilirubinconcentrations exceed exchange levels Appropriate consultation should be obtained if the etiology ofhyperbilirubinemia is unclear the infant is ill and particularly if bilirubin concentrations are approachingexchange levels Because the risks of exchange transfusion are significant the best management may bereviewed with an expert opinion from a neonatologist
Conclusions Hyperbilirubinemia in apparently healthy term newborn infants continues to hold the potential threat ofcomplications from bilirubin encephalopathy and kernicterus Careful assessment of risk factors judicious useof phototherapy appropriate laboratory monitoring and specific treatment of other disorders (eg sepsis) areessential for the optimal management of hyperbilirubinemia Appropriate laboratory facilities must be availableto measure bilirubin concentrations for out-patients in required clinical situations Readmission to hospital maybe required if phototherapy is necessary Guidelines for phototherapy are presented for term babies with andwithout identifiable risk factors
References
1 Fetus and Newborn Committee Canadian Paediatric Society Use of phototherapy for neonatalhyperbilirubinemia Can Med Assoc J 19861341237-45 2 American Academy of Pediatrics Practice parameter Management of hyperbilirubinemia in the healthy termnewborn Pediatrics 199494558-65 3 Hansen TWR Therapeutical approaches to neonatal jaundice an international survey Clin Pediatr199635309-16 4 Valaes T Koliopoulos C Koltsidopoulos A The impact of phototherapy in the management of neonatalhyperbilirubinemia comparison of historical cohorts Acta Paediatrica 199685273-6 5 Gustafson PA Boyle DW Bilirubin index a new standard for intervention Med Hypotheses 199545409-16 6 Torres-Torres M Tayaba R Weintraub A Holzman IR New perspectives on neonatal hyperbilirubinemiaMount Sinai J Med 199461424-8 7 Lazar L Litwin A Merlob P Phototherapy for neonatal nonhemolytic hyperbilirubinemia analysis ofrebound and indications for discontinuing therapy Clin Pediatr 199332264-7 8 Newman TB Maisels MJ Evaluation and treatment of jaundice in the term newborn Pediatrics 199289809-18 9 McMillan DD Lockyer JM Magnan L Akierman A Parboosingh JT Effect of educational program andinterview on adoption of guidelines for the management of neonatal hyperbilirubinemia Can Med Assoc J1991144707-12 10 Brown AK Johnson L Loss of concern about jaundice and the reemergence of kernicterus in full-terminfants in the era of managed care In Fanaroff AA Klaus MH eds The Year Book of Neonatal and PerinatalMedicine Philadelphia Mosby Yearbook 199617-28 11 Valaes T Bilirubin toxicity The problem was solved a generation ago Pediatrics 199289819-21 12 Wennberg RP Bilirubin recommendations present problems New guidelines simplistic and untestedPediatrics 199289821-2 13 Merenstein GB lsquoNewrsquo bilirubin recommendations questioned Pediatrics 199289822-3 14 Poland RL In search of a lsquogold standardrsquo for bilirubin toxicity Pediatrics 199289823-4 15 Brown AK Seidman DS Stevenson DK Jaundice in healthy term neonates Do we need new action levelsor new approaches Pediatrics 199289827-9 16 Johnson L Yet another expert opinion on bilirubin toxicity Pediatrics 199289829-31
Jaundice in the Healthy Term Newborn
April 2002 Page 16 of 20
17 MacDonald MG Hidden risks Early discharge and bilirubin toxicity due to glucose-6-phosphatedehydrogenase deficiency Pediatrics 199596734-8 18 Maisels MJ Newman TB Kernicterus in otherwise healthy breast-fed newborns Pediatrics 199596730-3 19 Vogl TP Phototherapy of neonatal hyperbilirubinemia bilirubin in unexposed areas of the skin J Pediatr197485707-1020 Rubaltelli FF Carli M The effect of light on cutaneous bilirubin Biol Neonate 197118457-62 21 Sisson TR Kendall N Shaw E et al Phototherapy of jaundice in the newborn infant 2 Effect of variouslight intensities J Pediatr 19738135-8 22 Bonta BW Warshaw JB Importance of radiant flux in the treatment of hyperbilirubinemia failure ofoverhead phototherapy units in intensive care units Pediatrics 197657502-5 23 Warshaw JB Gagliardi J Patel A A comparison of fluorescent and non-fluorescent light source forphototherapy Pediatrics 198065795-8 24 Ennever JF Blue light green light white light more light treatment of neonatal jaundice Clin Perinatol199017467-8125 Auerbach KG Gartner LM Breastfeeding and human milk their association with jaundice in the neonateClin Perinatol 19871489-108 26 Maisels MJ Jaundice in the newborn Pediatr Rev 19823305-20 27 Ahlfors CE Criteria for exchange transfusion in jaundiced newborns Pediatrics 199493488-94 28 Odell GB Storey GNB Rosenberg LA Studies in kernicterus III The saturation of serum protein withbilirubin during neonatal life and its relationship to brain damage at 5 years J Pediatr 19707612-21 29 Wirth FH Goldberg KE Lubchenco LO The neurologic outcome of infants evaluated for unboundbilirubin Pediatr Res 19759385-91 30 Haber BA Lake AM Cholestatic jaundice in the newborn Clin Perinatol 199017483-506 31 Maisels MJ Newman TB Jaundice in full-term and near-term babies who leave the hospital within 36hours The pediatricianrsquos nemesis Clin Perinatol 199825295-302 32 Fetus and Newborn Committee Canadian Paediatric Society and Society of Obstetricians andGynaecologists of Canada Facilitating discharge home following a normal term birth Paediatr Child Health19961165-8
Fetus and Newborn Committee Members Drs John Watts Department of Paediatrics Childrenrsquos Hospital ndash Hamilton Health Sciences CentreHamilton Ontario (director responsible) Douglas McMillan Department of Pediatrics Foothills HospitalCalgary Alberta (chair) Arne Ohlsson Department of Paediatrics Mount Sinai Hospital Toronto Ontario(co-chair) Deborah Davis Childrenrsquos Hospital of Eastern Ontario Ottawa Ontario Daniel Faucher RoyalVictoria Hospital Montreal Quebec (principal author) John Van Aerde Stollery Childrenrsquos Health CentreEdmonton Alberta Michael Vincer IWK-Grace Health Centre Halifax Nova ScotiaConsultant Dr Michael C Klein University of British Columbia Vancouver British Columbia (College ofFamily Physicians of Canada)Liaisons Drs James Lemon Riley Childrenrsquos Hospital Indiana University Medical Center IndianapolisIndiana (American Academy of Pediatrics) Saroj Saigal Department of Paediatrics McMaster UniversityMedical Centre Childrenrsquos Hospital ndash Hamilton Health Sciences Centre Hamilton Ontario (CPS Neonatal-Perinatal Medicine Section) Cheryl Levitt Department of Family Medicine Childrenrsquos Hospital ndash HamiltonHealth Sciences Centre Hamilton Ontario (College of Family Physicians of Canada) Catherine McCourtDirector Bureau of Reproductive amp Child Health Laboratory Centre for Disease Control Ottawa Ontario(Health Canada) Mrs Debbie Fraser-Askin Winnipeg Manitoba (Neonatal Nurses) Dr Line LeducDepartment of Obstetrics-Gynecology Hocircpital Sainte-Justine Montreal Quebec (Society of Obstetricians andGynaecologists of Canada)
Disclaimer The recommendations in this position statement do not indicate an exclusive course oftreatment or procedure to be followed Variations taking into account individual circumstances may beappropriate
Jaundice in the Healthy Term Newborn
April 2002 Page 17 of 20
APPENDIX 3Hyperbilirubinemia Risk Designation for Term and Near-Term Well Newborns
Jaundice in the Healthy Term Newborn
April 2002 Page 18 of 20
APPENDIX 4
American Academy of Pediatrics 1994 Practice parameter Management ofHyperbilirubinemia in the Healthy Term Newborn Pediatrics 94(4) 558-565
(Chart and Algorithm)
Jaundice in the Healthy Term Newborn
April 2002 Page 19 of 20
AlgorithmPediatric clinician evaluatesterm newborn with jaundice
Does the infant have signs of underlyingserious illness (lethargy apnea tachypneatemperature instability behavior changeshepatosplenomegaly persistant vomiting
or persistent feeding difficulty)
1
2
Exit this algorithm to individualizedclinical evaluation including
assessment of jaundice and underlyingdisease
Yes
3
No
Is the infant lt 37 weeks gestational age
4 Exit this algorithm to individualizedclinical evaluation including
assessment of jaundice in light ofprematurity
5
Yes
Is the mothersABO and Rh
blood typing andisoimmune
antibody screenstatus known
Is the mothersblood Rhpositive
Does themothers blood
have anyimmune
antibodies
Consider holding the infantscord blood in the blood bank incase future testing is necessary
6 7 8 9No
Yes Yes No
(Go to Box 10) (Go to Box 10) (Go to Box 10) (Go to Box 13)
No No Yes
Perform blood typing (ABO and Rh) and direct Coombs testingon the infants cord (preferably) or venous blood
10
Is the infantsblood direct
Coombs testpositive
Exit this algorithm to individualized clinical evaluationincluding assessment of jaundice and isoimmune
hemolytic disease
11 12
Yes
Are any of the following risk factors present tosuggest that nonisoimmune hemolytic disease
is possible in this infant(1) Family history of hemolytic anemia
OR(2) Family history of early or severe jaundice
OR(3) Ethnicity or geographic originassociated with hemolytic anemia
OR(4) Early or severe jaundice
Perform appropriate laboratoryassessment of infant including
(but not limited to consideration of)(1) Complete blood count differentialsmear reticulocyte count(2) G6PD screen(3) Hemoglobin electrophoresis
1314
No
No
No
(Go to Box 16)
Does the evaluation suggesthemolytic disease
15
Yes
(Go to Box 17)(Go to Box 16)
No
Jaundice in the Healthy Term Newborn
April 2002 Page 20 of 20
AlgorithmIs the infant
jaundiced andlt 24 hours of
age
Exit this algorithm to individualizedclinical evaluation includingassessment of jaundice and
nonisoimmune hemolytic disease
Is jaundiceclinicallysignificant by medical
judgment
(1) Measure infantstotal serum bilirubin(2) Go to Box 27
Healthy term infant with jaundice not clinicallysignificant by medical judgment
Follow infant in routine clinical supervision
1617
18 19
20
21
(Go to Box 22)
Yes
Yes
No
No
Is jaundicepersisting
gt 2 weeks
Does this infant haveabnormal physicalexam results dark
urine or light stools
Is jaundice persistinggt 3 weeks
Perform appropriate physical andlaboratory assessment of theinfant including possibility of
cholestatic jaundice
Provide routine carerecommend routine
feeding and follow-up Table 2 Management of Hyperbilirubinemia in the Healthy Term NewbornAgehours TSB Level mgdL (umolL)
Consider Phototherapy Exchange ExchangePhototherapy Transfusion Transfusion
if Intensive and IntensivePhototherapy PhototherapyFails
lt24 25-48 gt 12 (170) gt15 (260) gt 20 (340) gt 25 (430)49-72 gt 15 (260) gt 18 (310) gt 25 (430) gt 30 (510)gt 72 gt 17 (290) gt 20 (340) gt 25 (430) gt 30 (510)
TSB indicates total serum bilirubinPhototherapy at these TSB levels is a clinical option meaning that the intervention is availableand may be used on the basis of individual clinical judgement For a more detailed descriptionof phototherapy see the AppendixIntensive phototherapy (Appendix) should produce a decline of TSB of 1 to 2 mgdL within 4 to 6hours and the TSB level should continue to fall and remain below the threshold level for exchangetransfusion If this does not occur it is considered a failure of phototherapyTerm infants who are clinically jaundiced at lt 24 hours old are not considered healthy andrequire further evaluation (see text)
22 23
24
25
26
YesYes
No
YesNo
No 27
Algorithm Management of hyperbilirubinemia inthe healthy term infant
(From Box 19)
Jaundice in the Healthy Term Newborn
April 2002 Page 14 of 20
Clinical management of hyperbilirubinemia in infants
A bilirubin level that justifies consideration of phototherapy should mandate the investigation of the cause ofhyperbilirubinemia Investigation should include a clinically pertinent history of the mother family historydescription of labour and delivery and infantrsquos clinical course (26) A physical examination should besupplemented by laboratory investigations (Table 1) including determination of unconjugated and conjugatedserum bilirubin concentrations and blood group with direct antibody test (Coombsrsquo test) and hemoglobin andhematocrit levels A complete blood count including differential white cell count and a blood smear for red cellmorphology may be indicated Further tests (eg reticulocyte count G6PD screen) may be indicated based oninitial results ethnicity or clinical presentation Testing for serum electrolytes and albumin or protein areindicated in some situations such as suspected dehydration or when bilirubin levels approach exchange valuesIn the absence of drugs or clinical states that alter the binding of bilirubin by albumin the bilirubin to albuminor the bilirubin to protein ratio reflects the free bilirubin concentration and the binding capacity of the serum(27-29) At a bilirubin concentration close to exchange transfusion levels some clinicians may wish to ensurethat serum bilirubin binding is normal (albumin 25 gL or greater protein 54 gL or greater) Values belowthese levels may be associated with low bilirubin binding and may be used by the clinician when decidingwhether further intervention (eg exchange transfusion) should take place (27)
TABLE 1 Laboratory investigation for hyperbilirubinemia in term newborn infants
Indicated (if bilirubin concentrations reach phototherapy levels) Serum total or unconjugated bilirubin concentration Serum conjugated bilirubin concentration Blood group with direct antibody test (Coombsrsquo test) Hemoglobin and hematocrit determinations
Optional (in specific clinical circumstances) Complete blood count including manual differential white cell count Blood smear for red cell morphology Reticulocyte count Glucose-6-phosphate dehydrogenase screen Serum electrolytes and albumin or protein concentrations
For infants with prolonged jaundice (lasting longer than seven days) or with conjugated hyperbilirubinemia(greater than 30 micromolL) additional investigation and management may be required and a consultation with aspecialist may be needed (30)
During the past decade most nurseries have shortened the time of hospital stay for term healthy newborninfants Early discharge of neonates means that jaundice is not often recognized at discharge (31) The CanadianPaediatric Society reiterates the importance of allowing early discharge only if a healthy status is confirmed foreach baby and appropriate follow-up is provided (32) Appropriate parental education about feeding signs ofdehydration and jaundice must be implemented in hospital nurseries Testing for serum bilirubin concentrationsmust be readily available for newborns on an out-patient basis Readmission to hospital (usually the hospital ofbirth) may be necessary for the investigation and management of hyperbilirubinemia
Exchange transfusion If phototherapy fails to control the rising bilirubin levels exchange transfusion is indicated to lower serumbilirubin concentrations For healthy term infants without risk factors exchange transfusion should beconsidered at serum unconjugated bilirubin concentrations of 400 to 430 micromolL For term infants with riskfactors the level should be 340 micromolL For infants who initially present with serum bilirubin concentrations in
Jaundice in the Healthy Term Newborn
April 2002 Page 15 of 20
excess of exchange levels intensive phototherapy should produce a decline of serum unconjugated bilirubinfrom 20 to 35 micromolL within 4 to 6 h and levels should continue to fall thereafter and remain below thethreshold for exchange transfusion If the bilirubin concentration does not decrease after adequate rehydrationand 4 to 6 h of intensive phototherapy exchange transfusion should be considered Preparation for thisincluding ensuring availability of blood should occur shortly after the admission of babies whose bilirubinconcentrations exceed exchange levels Appropriate consultation should be obtained if the etiology ofhyperbilirubinemia is unclear the infant is ill and particularly if bilirubin concentrations are approachingexchange levels Because the risks of exchange transfusion are significant the best management may bereviewed with an expert opinion from a neonatologist
Conclusions Hyperbilirubinemia in apparently healthy term newborn infants continues to hold the potential threat ofcomplications from bilirubin encephalopathy and kernicterus Careful assessment of risk factors judicious useof phototherapy appropriate laboratory monitoring and specific treatment of other disorders (eg sepsis) areessential for the optimal management of hyperbilirubinemia Appropriate laboratory facilities must be availableto measure bilirubin concentrations for out-patients in required clinical situations Readmission to hospital maybe required if phototherapy is necessary Guidelines for phototherapy are presented for term babies with andwithout identifiable risk factors
References
1 Fetus and Newborn Committee Canadian Paediatric Society Use of phototherapy for neonatalhyperbilirubinemia Can Med Assoc J 19861341237-45 2 American Academy of Pediatrics Practice parameter Management of hyperbilirubinemia in the healthy termnewborn Pediatrics 199494558-65 3 Hansen TWR Therapeutical approaches to neonatal jaundice an international survey Clin Pediatr199635309-16 4 Valaes T Koliopoulos C Koltsidopoulos A The impact of phototherapy in the management of neonatalhyperbilirubinemia comparison of historical cohorts Acta Paediatrica 199685273-6 5 Gustafson PA Boyle DW Bilirubin index a new standard for intervention Med Hypotheses 199545409-16 6 Torres-Torres M Tayaba R Weintraub A Holzman IR New perspectives on neonatal hyperbilirubinemiaMount Sinai J Med 199461424-8 7 Lazar L Litwin A Merlob P Phototherapy for neonatal nonhemolytic hyperbilirubinemia analysis ofrebound and indications for discontinuing therapy Clin Pediatr 199332264-7 8 Newman TB Maisels MJ Evaluation and treatment of jaundice in the term newborn Pediatrics 199289809-18 9 McMillan DD Lockyer JM Magnan L Akierman A Parboosingh JT Effect of educational program andinterview on adoption of guidelines for the management of neonatal hyperbilirubinemia Can Med Assoc J1991144707-12 10 Brown AK Johnson L Loss of concern about jaundice and the reemergence of kernicterus in full-terminfants in the era of managed care In Fanaroff AA Klaus MH eds The Year Book of Neonatal and PerinatalMedicine Philadelphia Mosby Yearbook 199617-28 11 Valaes T Bilirubin toxicity The problem was solved a generation ago Pediatrics 199289819-21 12 Wennberg RP Bilirubin recommendations present problems New guidelines simplistic and untestedPediatrics 199289821-2 13 Merenstein GB lsquoNewrsquo bilirubin recommendations questioned Pediatrics 199289822-3 14 Poland RL In search of a lsquogold standardrsquo for bilirubin toxicity Pediatrics 199289823-4 15 Brown AK Seidman DS Stevenson DK Jaundice in healthy term neonates Do we need new action levelsor new approaches Pediatrics 199289827-9 16 Johnson L Yet another expert opinion on bilirubin toxicity Pediatrics 199289829-31
Jaundice in the Healthy Term Newborn
April 2002 Page 16 of 20
17 MacDonald MG Hidden risks Early discharge and bilirubin toxicity due to glucose-6-phosphatedehydrogenase deficiency Pediatrics 199596734-8 18 Maisels MJ Newman TB Kernicterus in otherwise healthy breast-fed newborns Pediatrics 199596730-3 19 Vogl TP Phototherapy of neonatal hyperbilirubinemia bilirubin in unexposed areas of the skin J Pediatr197485707-1020 Rubaltelli FF Carli M The effect of light on cutaneous bilirubin Biol Neonate 197118457-62 21 Sisson TR Kendall N Shaw E et al Phototherapy of jaundice in the newborn infant 2 Effect of variouslight intensities J Pediatr 19738135-8 22 Bonta BW Warshaw JB Importance of radiant flux in the treatment of hyperbilirubinemia failure ofoverhead phototherapy units in intensive care units Pediatrics 197657502-5 23 Warshaw JB Gagliardi J Patel A A comparison of fluorescent and non-fluorescent light source forphototherapy Pediatrics 198065795-8 24 Ennever JF Blue light green light white light more light treatment of neonatal jaundice Clin Perinatol199017467-8125 Auerbach KG Gartner LM Breastfeeding and human milk their association with jaundice in the neonateClin Perinatol 19871489-108 26 Maisels MJ Jaundice in the newborn Pediatr Rev 19823305-20 27 Ahlfors CE Criteria for exchange transfusion in jaundiced newborns Pediatrics 199493488-94 28 Odell GB Storey GNB Rosenberg LA Studies in kernicterus III The saturation of serum protein withbilirubin during neonatal life and its relationship to brain damage at 5 years J Pediatr 19707612-21 29 Wirth FH Goldberg KE Lubchenco LO The neurologic outcome of infants evaluated for unboundbilirubin Pediatr Res 19759385-91 30 Haber BA Lake AM Cholestatic jaundice in the newborn Clin Perinatol 199017483-506 31 Maisels MJ Newman TB Jaundice in full-term and near-term babies who leave the hospital within 36hours The pediatricianrsquos nemesis Clin Perinatol 199825295-302 32 Fetus and Newborn Committee Canadian Paediatric Society and Society of Obstetricians andGynaecologists of Canada Facilitating discharge home following a normal term birth Paediatr Child Health19961165-8
Fetus and Newborn Committee Members Drs John Watts Department of Paediatrics Childrenrsquos Hospital ndash Hamilton Health Sciences CentreHamilton Ontario (director responsible) Douglas McMillan Department of Pediatrics Foothills HospitalCalgary Alberta (chair) Arne Ohlsson Department of Paediatrics Mount Sinai Hospital Toronto Ontario(co-chair) Deborah Davis Childrenrsquos Hospital of Eastern Ontario Ottawa Ontario Daniel Faucher RoyalVictoria Hospital Montreal Quebec (principal author) John Van Aerde Stollery Childrenrsquos Health CentreEdmonton Alberta Michael Vincer IWK-Grace Health Centre Halifax Nova ScotiaConsultant Dr Michael C Klein University of British Columbia Vancouver British Columbia (College ofFamily Physicians of Canada)Liaisons Drs James Lemon Riley Childrenrsquos Hospital Indiana University Medical Center IndianapolisIndiana (American Academy of Pediatrics) Saroj Saigal Department of Paediatrics McMaster UniversityMedical Centre Childrenrsquos Hospital ndash Hamilton Health Sciences Centre Hamilton Ontario (CPS Neonatal-Perinatal Medicine Section) Cheryl Levitt Department of Family Medicine Childrenrsquos Hospital ndash HamiltonHealth Sciences Centre Hamilton Ontario (College of Family Physicians of Canada) Catherine McCourtDirector Bureau of Reproductive amp Child Health Laboratory Centre for Disease Control Ottawa Ontario(Health Canada) Mrs Debbie Fraser-Askin Winnipeg Manitoba (Neonatal Nurses) Dr Line LeducDepartment of Obstetrics-Gynecology Hocircpital Sainte-Justine Montreal Quebec (Society of Obstetricians andGynaecologists of Canada)
Disclaimer The recommendations in this position statement do not indicate an exclusive course oftreatment or procedure to be followed Variations taking into account individual circumstances may beappropriate
Jaundice in the Healthy Term Newborn
April 2002 Page 17 of 20
APPENDIX 3Hyperbilirubinemia Risk Designation for Term and Near-Term Well Newborns
Jaundice in the Healthy Term Newborn
April 2002 Page 18 of 20
APPENDIX 4
American Academy of Pediatrics 1994 Practice parameter Management ofHyperbilirubinemia in the Healthy Term Newborn Pediatrics 94(4) 558-565
(Chart and Algorithm)
Jaundice in the Healthy Term Newborn
April 2002 Page 19 of 20
AlgorithmPediatric clinician evaluatesterm newborn with jaundice
Does the infant have signs of underlyingserious illness (lethargy apnea tachypneatemperature instability behavior changeshepatosplenomegaly persistant vomiting
or persistent feeding difficulty)
1
2
Exit this algorithm to individualizedclinical evaluation including
assessment of jaundice and underlyingdisease
Yes
3
No
Is the infant lt 37 weeks gestational age
4 Exit this algorithm to individualizedclinical evaluation including
assessment of jaundice in light ofprematurity
5
Yes
Is the mothersABO and Rh
blood typing andisoimmune
antibody screenstatus known
Is the mothersblood Rhpositive
Does themothers blood
have anyimmune
antibodies
Consider holding the infantscord blood in the blood bank incase future testing is necessary
6 7 8 9No
Yes Yes No
(Go to Box 10) (Go to Box 10) (Go to Box 10) (Go to Box 13)
No No Yes
Perform blood typing (ABO and Rh) and direct Coombs testingon the infants cord (preferably) or venous blood
10
Is the infantsblood direct
Coombs testpositive
Exit this algorithm to individualized clinical evaluationincluding assessment of jaundice and isoimmune
hemolytic disease
11 12
Yes
Are any of the following risk factors present tosuggest that nonisoimmune hemolytic disease
is possible in this infant(1) Family history of hemolytic anemia
OR(2) Family history of early or severe jaundice
OR(3) Ethnicity or geographic originassociated with hemolytic anemia
OR(4) Early or severe jaundice
Perform appropriate laboratoryassessment of infant including
(but not limited to consideration of)(1) Complete blood count differentialsmear reticulocyte count(2) G6PD screen(3) Hemoglobin electrophoresis
1314
No
No
No
(Go to Box 16)
Does the evaluation suggesthemolytic disease
15
Yes
(Go to Box 17)(Go to Box 16)
No
Jaundice in the Healthy Term Newborn
April 2002 Page 20 of 20
AlgorithmIs the infant
jaundiced andlt 24 hours of
age
Exit this algorithm to individualizedclinical evaluation includingassessment of jaundice and
nonisoimmune hemolytic disease
Is jaundiceclinicallysignificant by medical
judgment
(1) Measure infantstotal serum bilirubin(2) Go to Box 27
Healthy term infant with jaundice not clinicallysignificant by medical judgment
Follow infant in routine clinical supervision
1617
18 19
20
21
(Go to Box 22)
Yes
Yes
No
No
Is jaundicepersisting
gt 2 weeks
Does this infant haveabnormal physicalexam results dark
urine or light stools
Is jaundice persistinggt 3 weeks
Perform appropriate physical andlaboratory assessment of theinfant including possibility of
cholestatic jaundice
Provide routine carerecommend routine
feeding and follow-up Table 2 Management of Hyperbilirubinemia in the Healthy Term NewbornAgehours TSB Level mgdL (umolL)
Consider Phototherapy Exchange ExchangePhototherapy Transfusion Transfusion
if Intensive and IntensivePhototherapy PhototherapyFails
lt24 25-48 gt 12 (170) gt15 (260) gt 20 (340) gt 25 (430)49-72 gt 15 (260) gt 18 (310) gt 25 (430) gt 30 (510)gt 72 gt 17 (290) gt 20 (340) gt 25 (430) gt 30 (510)
TSB indicates total serum bilirubinPhototherapy at these TSB levels is a clinical option meaning that the intervention is availableand may be used on the basis of individual clinical judgement For a more detailed descriptionof phototherapy see the AppendixIntensive phototherapy (Appendix) should produce a decline of TSB of 1 to 2 mgdL within 4 to 6hours and the TSB level should continue to fall and remain below the threshold level for exchangetransfusion If this does not occur it is considered a failure of phototherapyTerm infants who are clinically jaundiced at lt 24 hours old are not considered healthy andrequire further evaluation (see text)
22 23
24
25
26
YesYes
No
YesNo
No 27
Algorithm Management of hyperbilirubinemia inthe healthy term infant
(From Box 19)
Jaundice in the Healthy Term Newborn
April 2002 Page 15 of 20
excess of exchange levels intensive phototherapy should produce a decline of serum unconjugated bilirubinfrom 20 to 35 micromolL within 4 to 6 h and levels should continue to fall thereafter and remain below thethreshold for exchange transfusion If the bilirubin concentration does not decrease after adequate rehydrationand 4 to 6 h of intensive phototherapy exchange transfusion should be considered Preparation for thisincluding ensuring availability of blood should occur shortly after the admission of babies whose bilirubinconcentrations exceed exchange levels Appropriate consultation should be obtained if the etiology ofhyperbilirubinemia is unclear the infant is ill and particularly if bilirubin concentrations are approachingexchange levels Because the risks of exchange transfusion are significant the best management may bereviewed with an expert opinion from a neonatologist
Conclusions Hyperbilirubinemia in apparently healthy term newborn infants continues to hold the potential threat ofcomplications from bilirubin encephalopathy and kernicterus Careful assessment of risk factors judicious useof phototherapy appropriate laboratory monitoring and specific treatment of other disorders (eg sepsis) areessential for the optimal management of hyperbilirubinemia Appropriate laboratory facilities must be availableto measure bilirubin concentrations for out-patients in required clinical situations Readmission to hospital maybe required if phototherapy is necessary Guidelines for phototherapy are presented for term babies with andwithout identifiable risk factors
References
1 Fetus and Newborn Committee Canadian Paediatric Society Use of phototherapy for neonatalhyperbilirubinemia Can Med Assoc J 19861341237-45 2 American Academy of Pediatrics Practice parameter Management of hyperbilirubinemia in the healthy termnewborn Pediatrics 199494558-65 3 Hansen TWR Therapeutical approaches to neonatal jaundice an international survey Clin Pediatr199635309-16 4 Valaes T Koliopoulos C Koltsidopoulos A The impact of phototherapy in the management of neonatalhyperbilirubinemia comparison of historical cohorts Acta Paediatrica 199685273-6 5 Gustafson PA Boyle DW Bilirubin index a new standard for intervention Med Hypotheses 199545409-16 6 Torres-Torres M Tayaba R Weintraub A Holzman IR New perspectives on neonatal hyperbilirubinemiaMount Sinai J Med 199461424-8 7 Lazar L Litwin A Merlob P Phototherapy for neonatal nonhemolytic hyperbilirubinemia analysis ofrebound and indications for discontinuing therapy Clin Pediatr 199332264-7 8 Newman TB Maisels MJ Evaluation and treatment of jaundice in the term newborn Pediatrics 199289809-18 9 McMillan DD Lockyer JM Magnan L Akierman A Parboosingh JT Effect of educational program andinterview on adoption of guidelines for the management of neonatal hyperbilirubinemia Can Med Assoc J1991144707-12 10 Brown AK Johnson L Loss of concern about jaundice and the reemergence of kernicterus in full-terminfants in the era of managed care In Fanaroff AA Klaus MH eds The Year Book of Neonatal and PerinatalMedicine Philadelphia Mosby Yearbook 199617-28 11 Valaes T Bilirubin toxicity The problem was solved a generation ago Pediatrics 199289819-21 12 Wennberg RP Bilirubin recommendations present problems New guidelines simplistic and untestedPediatrics 199289821-2 13 Merenstein GB lsquoNewrsquo bilirubin recommendations questioned Pediatrics 199289822-3 14 Poland RL In search of a lsquogold standardrsquo for bilirubin toxicity Pediatrics 199289823-4 15 Brown AK Seidman DS Stevenson DK Jaundice in healthy term neonates Do we need new action levelsor new approaches Pediatrics 199289827-9 16 Johnson L Yet another expert opinion on bilirubin toxicity Pediatrics 199289829-31
Jaundice in the Healthy Term Newborn
April 2002 Page 16 of 20
17 MacDonald MG Hidden risks Early discharge and bilirubin toxicity due to glucose-6-phosphatedehydrogenase deficiency Pediatrics 199596734-8 18 Maisels MJ Newman TB Kernicterus in otherwise healthy breast-fed newborns Pediatrics 199596730-3 19 Vogl TP Phototherapy of neonatal hyperbilirubinemia bilirubin in unexposed areas of the skin J Pediatr197485707-1020 Rubaltelli FF Carli M The effect of light on cutaneous bilirubin Biol Neonate 197118457-62 21 Sisson TR Kendall N Shaw E et al Phototherapy of jaundice in the newborn infant 2 Effect of variouslight intensities J Pediatr 19738135-8 22 Bonta BW Warshaw JB Importance of radiant flux in the treatment of hyperbilirubinemia failure ofoverhead phototherapy units in intensive care units Pediatrics 197657502-5 23 Warshaw JB Gagliardi J Patel A A comparison of fluorescent and non-fluorescent light source forphototherapy Pediatrics 198065795-8 24 Ennever JF Blue light green light white light more light treatment of neonatal jaundice Clin Perinatol199017467-8125 Auerbach KG Gartner LM Breastfeeding and human milk their association with jaundice in the neonateClin Perinatol 19871489-108 26 Maisels MJ Jaundice in the newborn Pediatr Rev 19823305-20 27 Ahlfors CE Criteria for exchange transfusion in jaundiced newborns Pediatrics 199493488-94 28 Odell GB Storey GNB Rosenberg LA Studies in kernicterus III The saturation of serum protein withbilirubin during neonatal life and its relationship to brain damage at 5 years J Pediatr 19707612-21 29 Wirth FH Goldberg KE Lubchenco LO The neurologic outcome of infants evaluated for unboundbilirubin Pediatr Res 19759385-91 30 Haber BA Lake AM Cholestatic jaundice in the newborn Clin Perinatol 199017483-506 31 Maisels MJ Newman TB Jaundice in full-term and near-term babies who leave the hospital within 36hours The pediatricianrsquos nemesis Clin Perinatol 199825295-302 32 Fetus and Newborn Committee Canadian Paediatric Society and Society of Obstetricians andGynaecologists of Canada Facilitating discharge home following a normal term birth Paediatr Child Health19961165-8
Fetus and Newborn Committee Members Drs John Watts Department of Paediatrics Childrenrsquos Hospital ndash Hamilton Health Sciences CentreHamilton Ontario (director responsible) Douglas McMillan Department of Pediatrics Foothills HospitalCalgary Alberta (chair) Arne Ohlsson Department of Paediatrics Mount Sinai Hospital Toronto Ontario(co-chair) Deborah Davis Childrenrsquos Hospital of Eastern Ontario Ottawa Ontario Daniel Faucher RoyalVictoria Hospital Montreal Quebec (principal author) John Van Aerde Stollery Childrenrsquos Health CentreEdmonton Alberta Michael Vincer IWK-Grace Health Centre Halifax Nova ScotiaConsultant Dr Michael C Klein University of British Columbia Vancouver British Columbia (College ofFamily Physicians of Canada)Liaisons Drs James Lemon Riley Childrenrsquos Hospital Indiana University Medical Center IndianapolisIndiana (American Academy of Pediatrics) Saroj Saigal Department of Paediatrics McMaster UniversityMedical Centre Childrenrsquos Hospital ndash Hamilton Health Sciences Centre Hamilton Ontario (CPS Neonatal-Perinatal Medicine Section) Cheryl Levitt Department of Family Medicine Childrenrsquos Hospital ndash HamiltonHealth Sciences Centre Hamilton Ontario (College of Family Physicians of Canada) Catherine McCourtDirector Bureau of Reproductive amp Child Health Laboratory Centre for Disease Control Ottawa Ontario(Health Canada) Mrs Debbie Fraser-Askin Winnipeg Manitoba (Neonatal Nurses) Dr Line LeducDepartment of Obstetrics-Gynecology Hocircpital Sainte-Justine Montreal Quebec (Society of Obstetricians andGynaecologists of Canada)
Disclaimer The recommendations in this position statement do not indicate an exclusive course oftreatment or procedure to be followed Variations taking into account individual circumstances may beappropriate
Jaundice in the Healthy Term Newborn
April 2002 Page 17 of 20
APPENDIX 3Hyperbilirubinemia Risk Designation for Term and Near-Term Well Newborns
Jaundice in the Healthy Term Newborn
April 2002 Page 18 of 20
APPENDIX 4
American Academy of Pediatrics 1994 Practice parameter Management ofHyperbilirubinemia in the Healthy Term Newborn Pediatrics 94(4) 558-565
(Chart and Algorithm)
Jaundice in the Healthy Term Newborn
April 2002 Page 19 of 20
AlgorithmPediatric clinician evaluatesterm newborn with jaundice
Does the infant have signs of underlyingserious illness (lethargy apnea tachypneatemperature instability behavior changeshepatosplenomegaly persistant vomiting
or persistent feeding difficulty)
1
2
Exit this algorithm to individualizedclinical evaluation including
assessment of jaundice and underlyingdisease
Yes
3
No
Is the infant lt 37 weeks gestational age
4 Exit this algorithm to individualizedclinical evaluation including
assessment of jaundice in light ofprematurity
5
Yes
Is the mothersABO and Rh
blood typing andisoimmune
antibody screenstatus known
Is the mothersblood Rhpositive
Does themothers blood
have anyimmune
antibodies
Consider holding the infantscord blood in the blood bank incase future testing is necessary
6 7 8 9No
Yes Yes No
(Go to Box 10) (Go to Box 10) (Go to Box 10) (Go to Box 13)
No No Yes
Perform blood typing (ABO and Rh) and direct Coombs testingon the infants cord (preferably) or venous blood
10
Is the infantsblood direct
Coombs testpositive
Exit this algorithm to individualized clinical evaluationincluding assessment of jaundice and isoimmune
hemolytic disease
11 12
Yes
Are any of the following risk factors present tosuggest that nonisoimmune hemolytic disease
is possible in this infant(1) Family history of hemolytic anemia
OR(2) Family history of early or severe jaundice
OR(3) Ethnicity or geographic originassociated with hemolytic anemia
OR(4) Early or severe jaundice
Perform appropriate laboratoryassessment of infant including
(but not limited to consideration of)(1) Complete blood count differentialsmear reticulocyte count(2) G6PD screen(3) Hemoglobin electrophoresis
1314
No
No
No
(Go to Box 16)
Does the evaluation suggesthemolytic disease
15
Yes
(Go to Box 17)(Go to Box 16)
No
Jaundice in the Healthy Term Newborn
April 2002 Page 20 of 20
AlgorithmIs the infant
jaundiced andlt 24 hours of
age
Exit this algorithm to individualizedclinical evaluation includingassessment of jaundice and
nonisoimmune hemolytic disease
Is jaundiceclinicallysignificant by medical
judgment
(1) Measure infantstotal serum bilirubin(2) Go to Box 27
Healthy term infant with jaundice not clinicallysignificant by medical judgment
Follow infant in routine clinical supervision
1617
18 19
20
21
(Go to Box 22)
Yes
Yes
No
No
Is jaundicepersisting
gt 2 weeks
Does this infant haveabnormal physicalexam results dark
urine or light stools
Is jaundice persistinggt 3 weeks
Perform appropriate physical andlaboratory assessment of theinfant including possibility of
cholestatic jaundice
Provide routine carerecommend routine
feeding and follow-up Table 2 Management of Hyperbilirubinemia in the Healthy Term NewbornAgehours TSB Level mgdL (umolL)
Consider Phototherapy Exchange ExchangePhototherapy Transfusion Transfusion
if Intensive and IntensivePhototherapy PhototherapyFails
lt24 25-48 gt 12 (170) gt15 (260) gt 20 (340) gt 25 (430)49-72 gt 15 (260) gt 18 (310) gt 25 (430) gt 30 (510)gt 72 gt 17 (290) gt 20 (340) gt 25 (430) gt 30 (510)
TSB indicates total serum bilirubinPhototherapy at these TSB levels is a clinical option meaning that the intervention is availableand may be used on the basis of individual clinical judgement For a more detailed descriptionof phototherapy see the AppendixIntensive phototherapy (Appendix) should produce a decline of TSB of 1 to 2 mgdL within 4 to 6hours and the TSB level should continue to fall and remain below the threshold level for exchangetransfusion If this does not occur it is considered a failure of phototherapyTerm infants who are clinically jaundiced at lt 24 hours old are not considered healthy andrequire further evaluation (see text)
22 23
24
25
26
YesYes
No
YesNo
No 27
Algorithm Management of hyperbilirubinemia inthe healthy term infant
(From Box 19)
Jaundice in the Healthy Term Newborn
April 2002 Page 16 of 20
17 MacDonald MG Hidden risks Early discharge and bilirubin toxicity due to glucose-6-phosphatedehydrogenase deficiency Pediatrics 199596734-8 18 Maisels MJ Newman TB Kernicterus in otherwise healthy breast-fed newborns Pediatrics 199596730-3 19 Vogl TP Phototherapy of neonatal hyperbilirubinemia bilirubin in unexposed areas of the skin J Pediatr197485707-1020 Rubaltelli FF Carli M The effect of light on cutaneous bilirubin Biol Neonate 197118457-62 21 Sisson TR Kendall N Shaw E et al Phototherapy of jaundice in the newborn infant 2 Effect of variouslight intensities J Pediatr 19738135-8 22 Bonta BW Warshaw JB Importance of radiant flux in the treatment of hyperbilirubinemia failure ofoverhead phototherapy units in intensive care units Pediatrics 197657502-5 23 Warshaw JB Gagliardi J Patel A A comparison of fluorescent and non-fluorescent light source forphototherapy Pediatrics 198065795-8 24 Ennever JF Blue light green light white light more light treatment of neonatal jaundice Clin Perinatol199017467-8125 Auerbach KG Gartner LM Breastfeeding and human milk their association with jaundice in the neonateClin Perinatol 19871489-108 26 Maisels MJ Jaundice in the newborn Pediatr Rev 19823305-20 27 Ahlfors CE Criteria for exchange transfusion in jaundiced newborns Pediatrics 199493488-94 28 Odell GB Storey GNB Rosenberg LA Studies in kernicterus III The saturation of serum protein withbilirubin during neonatal life and its relationship to brain damage at 5 years J Pediatr 19707612-21 29 Wirth FH Goldberg KE Lubchenco LO The neurologic outcome of infants evaluated for unboundbilirubin Pediatr Res 19759385-91 30 Haber BA Lake AM Cholestatic jaundice in the newborn Clin Perinatol 199017483-506 31 Maisels MJ Newman TB Jaundice in full-term and near-term babies who leave the hospital within 36hours The pediatricianrsquos nemesis Clin Perinatol 199825295-302 32 Fetus and Newborn Committee Canadian Paediatric Society and Society of Obstetricians andGynaecologists of Canada Facilitating discharge home following a normal term birth Paediatr Child Health19961165-8
Fetus and Newborn Committee Members Drs John Watts Department of Paediatrics Childrenrsquos Hospital ndash Hamilton Health Sciences CentreHamilton Ontario (director responsible) Douglas McMillan Department of Pediatrics Foothills HospitalCalgary Alberta (chair) Arne Ohlsson Department of Paediatrics Mount Sinai Hospital Toronto Ontario(co-chair) Deborah Davis Childrenrsquos Hospital of Eastern Ontario Ottawa Ontario Daniel Faucher RoyalVictoria Hospital Montreal Quebec (principal author) John Van Aerde Stollery Childrenrsquos Health CentreEdmonton Alberta Michael Vincer IWK-Grace Health Centre Halifax Nova ScotiaConsultant Dr Michael C Klein University of British Columbia Vancouver British Columbia (College ofFamily Physicians of Canada)Liaisons Drs James Lemon Riley Childrenrsquos Hospital Indiana University Medical Center IndianapolisIndiana (American Academy of Pediatrics) Saroj Saigal Department of Paediatrics McMaster UniversityMedical Centre Childrenrsquos Hospital ndash Hamilton Health Sciences Centre Hamilton Ontario (CPS Neonatal-Perinatal Medicine Section) Cheryl Levitt Department of Family Medicine Childrenrsquos Hospital ndash HamiltonHealth Sciences Centre Hamilton Ontario (College of Family Physicians of Canada) Catherine McCourtDirector Bureau of Reproductive amp Child Health Laboratory Centre for Disease Control Ottawa Ontario(Health Canada) Mrs Debbie Fraser-Askin Winnipeg Manitoba (Neonatal Nurses) Dr Line LeducDepartment of Obstetrics-Gynecology Hocircpital Sainte-Justine Montreal Quebec (Society of Obstetricians andGynaecologists of Canada)
Disclaimer The recommendations in this position statement do not indicate an exclusive course oftreatment or procedure to be followed Variations taking into account individual circumstances may beappropriate
Jaundice in the Healthy Term Newborn
April 2002 Page 17 of 20
APPENDIX 3Hyperbilirubinemia Risk Designation for Term and Near-Term Well Newborns
Jaundice in the Healthy Term Newborn
April 2002 Page 18 of 20
APPENDIX 4
American Academy of Pediatrics 1994 Practice parameter Management ofHyperbilirubinemia in the Healthy Term Newborn Pediatrics 94(4) 558-565
(Chart and Algorithm)
Jaundice in the Healthy Term Newborn
April 2002 Page 19 of 20
AlgorithmPediatric clinician evaluatesterm newborn with jaundice
Does the infant have signs of underlyingserious illness (lethargy apnea tachypneatemperature instability behavior changeshepatosplenomegaly persistant vomiting
or persistent feeding difficulty)
1
2
Exit this algorithm to individualizedclinical evaluation including
assessment of jaundice and underlyingdisease
Yes
3
No
Is the infant lt 37 weeks gestational age
4 Exit this algorithm to individualizedclinical evaluation including
assessment of jaundice in light ofprematurity
5
Yes
Is the mothersABO and Rh
blood typing andisoimmune
antibody screenstatus known
Is the mothersblood Rhpositive
Does themothers blood
have anyimmune
antibodies
Consider holding the infantscord blood in the blood bank incase future testing is necessary
6 7 8 9No
Yes Yes No
(Go to Box 10) (Go to Box 10) (Go to Box 10) (Go to Box 13)
No No Yes
Perform blood typing (ABO and Rh) and direct Coombs testingon the infants cord (preferably) or venous blood
10
Is the infantsblood direct
Coombs testpositive
Exit this algorithm to individualized clinical evaluationincluding assessment of jaundice and isoimmune
hemolytic disease
11 12
Yes
Are any of the following risk factors present tosuggest that nonisoimmune hemolytic disease
is possible in this infant(1) Family history of hemolytic anemia
OR(2) Family history of early or severe jaundice
OR(3) Ethnicity or geographic originassociated with hemolytic anemia
OR(4) Early or severe jaundice
Perform appropriate laboratoryassessment of infant including
(but not limited to consideration of)(1) Complete blood count differentialsmear reticulocyte count(2) G6PD screen(3) Hemoglobin electrophoresis
1314
No
No
No
(Go to Box 16)
Does the evaluation suggesthemolytic disease
15
Yes
(Go to Box 17)(Go to Box 16)
No
Jaundice in the Healthy Term Newborn
April 2002 Page 20 of 20
AlgorithmIs the infant
jaundiced andlt 24 hours of
age
Exit this algorithm to individualizedclinical evaluation includingassessment of jaundice and
nonisoimmune hemolytic disease
Is jaundiceclinicallysignificant by medical
judgment
(1) Measure infantstotal serum bilirubin(2) Go to Box 27
Healthy term infant with jaundice not clinicallysignificant by medical judgment
Follow infant in routine clinical supervision
1617
18 19
20
21
(Go to Box 22)
Yes
Yes
No
No
Is jaundicepersisting
gt 2 weeks
Does this infant haveabnormal physicalexam results dark
urine or light stools
Is jaundice persistinggt 3 weeks
Perform appropriate physical andlaboratory assessment of theinfant including possibility of
cholestatic jaundice
Provide routine carerecommend routine
feeding and follow-up Table 2 Management of Hyperbilirubinemia in the Healthy Term NewbornAgehours TSB Level mgdL (umolL)
Consider Phototherapy Exchange ExchangePhototherapy Transfusion Transfusion
if Intensive and IntensivePhototherapy PhototherapyFails
lt24 25-48 gt 12 (170) gt15 (260) gt 20 (340) gt 25 (430)49-72 gt 15 (260) gt 18 (310) gt 25 (430) gt 30 (510)gt 72 gt 17 (290) gt 20 (340) gt 25 (430) gt 30 (510)
TSB indicates total serum bilirubinPhototherapy at these TSB levels is a clinical option meaning that the intervention is availableand may be used on the basis of individual clinical judgement For a more detailed descriptionof phototherapy see the AppendixIntensive phototherapy (Appendix) should produce a decline of TSB of 1 to 2 mgdL within 4 to 6hours and the TSB level should continue to fall and remain below the threshold level for exchangetransfusion If this does not occur it is considered a failure of phototherapyTerm infants who are clinically jaundiced at lt 24 hours old are not considered healthy andrequire further evaluation (see text)
22 23
24
25
26
YesYes
No
YesNo
No 27
Algorithm Management of hyperbilirubinemia inthe healthy term infant
(From Box 19)
Jaundice in the Healthy Term Newborn
April 2002 Page 17 of 20
APPENDIX 3Hyperbilirubinemia Risk Designation for Term and Near-Term Well Newborns
Jaundice in the Healthy Term Newborn
April 2002 Page 18 of 20
APPENDIX 4
American Academy of Pediatrics 1994 Practice parameter Management ofHyperbilirubinemia in the Healthy Term Newborn Pediatrics 94(4) 558-565
(Chart and Algorithm)
Jaundice in the Healthy Term Newborn
April 2002 Page 19 of 20
AlgorithmPediatric clinician evaluatesterm newborn with jaundice
Does the infant have signs of underlyingserious illness (lethargy apnea tachypneatemperature instability behavior changeshepatosplenomegaly persistant vomiting
or persistent feeding difficulty)
1
2
Exit this algorithm to individualizedclinical evaluation including
assessment of jaundice and underlyingdisease
Yes
3
No
Is the infant lt 37 weeks gestational age
4 Exit this algorithm to individualizedclinical evaluation including
assessment of jaundice in light ofprematurity
5
Yes
Is the mothersABO and Rh
blood typing andisoimmune
antibody screenstatus known
Is the mothersblood Rhpositive
Does themothers blood
have anyimmune
antibodies
Consider holding the infantscord blood in the blood bank incase future testing is necessary
6 7 8 9No
Yes Yes No
(Go to Box 10) (Go to Box 10) (Go to Box 10) (Go to Box 13)
No No Yes
Perform blood typing (ABO and Rh) and direct Coombs testingon the infants cord (preferably) or venous blood
10
Is the infantsblood direct
Coombs testpositive
Exit this algorithm to individualized clinical evaluationincluding assessment of jaundice and isoimmune
hemolytic disease
11 12
Yes
Are any of the following risk factors present tosuggest that nonisoimmune hemolytic disease
is possible in this infant(1) Family history of hemolytic anemia
OR(2) Family history of early or severe jaundice
OR(3) Ethnicity or geographic originassociated with hemolytic anemia
OR(4) Early or severe jaundice
Perform appropriate laboratoryassessment of infant including
(but not limited to consideration of)(1) Complete blood count differentialsmear reticulocyte count(2) G6PD screen(3) Hemoglobin electrophoresis
1314
No
No
No
(Go to Box 16)
Does the evaluation suggesthemolytic disease
15
Yes
(Go to Box 17)(Go to Box 16)
No
Jaundice in the Healthy Term Newborn
April 2002 Page 20 of 20
AlgorithmIs the infant
jaundiced andlt 24 hours of
age
Exit this algorithm to individualizedclinical evaluation includingassessment of jaundice and
nonisoimmune hemolytic disease
Is jaundiceclinicallysignificant by medical
judgment
(1) Measure infantstotal serum bilirubin(2) Go to Box 27
Healthy term infant with jaundice not clinicallysignificant by medical judgment
Follow infant in routine clinical supervision
1617
18 19
20
21
(Go to Box 22)
Yes
Yes
No
No
Is jaundicepersisting
gt 2 weeks
Does this infant haveabnormal physicalexam results dark
urine or light stools
Is jaundice persistinggt 3 weeks
Perform appropriate physical andlaboratory assessment of theinfant including possibility of
cholestatic jaundice
Provide routine carerecommend routine
feeding and follow-up Table 2 Management of Hyperbilirubinemia in the Healthy Term NewbornAgehours TSB Level mgdL (umolL)
Consider Phototherapy Exchange ExchangePhototherapy Transfusion Transfusion
if Intensive and IntensivePhototherapy PhototherapyFails
lt24 25-48 gt 12 (170) gt15 (260) gt 20 (340) gt 25 (430)49-72 gt 15 (260) gt 18 (310) gt 25 (430) gt 30 (510)gt 72 gt 17 (290) gt 20 (340) gt 25 (430) gt 30 (510)
TSB indicates total serum bilirubinPhototherapy at these TSB levels is a clinical option meaning that the intervention is availableand may be used on the basis of individual clinical judgement For a more detailed descriptionof phototherapy see the AppendixIntensive phototherapy (Appendix) should produce a decline of TSB of 1 to 2 mgdL within 4 to 6hours and the TSB level should continue to fall and remain below the threshold level for exchangetransfusion If this does not occur it is considered a failure of phototherapyTerm infants who are clinically jaundiced at lt 24 hours old are not considered healthy andrequire further evaluation (see text)
22 23
24
25
26
YesYes
No
YesNo
No 27
Algorithm Management of hyperbilirubinemia inthe healthy term infant
(From Box 19)
Jaundice in the Healthy Term Newborn
April 2002 Page 18 of 20
APPENDIX 4
American Academy of Pediatrics 1994 Practice parameter Management ofHyperbilirubinemia in the Healthy Term Newborn Pediatrics 94(4) 558-565
(Chart and Algorithm)
Jaundice in the Healthy Term Newborn
April 2002 Page 19 of 20
AlgorithmPediatric clinician evaluatesterm newborn with jaundice
Does the infant have signs of underlyingserious illness (lethargy apnea tachypneatemperature instability behavior changeshepatosplenomegaly persistant vomiting
or persistent feeding difficulty)
1
2
Exit this algorithm to individualizedclinical evaluation including
assessment of jaundice and underlyingdisease
Yes
3
No
Is the infant lt 37 weeks gestational age
4 Exit this algorithm to individualizedclinical evaluation including
assessment of jaundice in light ofprematurity
5
Yes
Is the mothersABO and Rh
blood typing andisoimmune
antibody screenstatus known
Is the mothersblood Rhpositive
Does themothers blood
have anyimmune
antibodies
Consider holding the infantscord blood in the blood bank incase future testing is necessary
6 7 8 9No
Yes Yes No
(Go to Box 10) (Go to Box 10) (Go to Box 10) (Go to Box 13)
No No Yes
Perform blood typing (ABO and Rh) and direct Coombs testingon the infants cord (preferably) or venous blood
10
Is the infantsblood direct
Coombs testpositive
Exit this algorithm to individualized clinical evaluationincluding assessment of jaundice and isoimmune
hemolytic disease
11 12
Yes
Are any of the following risk factors present tosuggest that nonisoimmune hemolytic disease
is possible in this infant(1) Family history of hemolytic anemia
OR(2) Family history of early or severe jaundice
OR(3) Ethnicity or geographic originassociated with hemolytic anemia
OR(4) Early or severe jaundice
Perform appropriate laboratoryassessment of infant including
(but not limited to consideration of)(1) Complete blood count differentialsmear reticulocyte count(2) G6PD screen(3) Hemoglobin electrophoresis
1314
No
No
No
(Go to Box 16)
Does the evaluation suggesthemolytic disease
15
Yes
(Go to Box 17)(Go to Box 16)
No
Jaundice in the Healthy Term Newborn
April 2002 Page 20 of 20
AlgorithmIs the infant
jaundiced andlt 24 hours of
age
Exit this algorithm to individualizedclinical evaluation includingassessment of jaundice and
nonisoimmune hemolytic disease
Is jaundiceclinicallysignificant by medical
judgment
(1) Measure infantstotal serum bilirubin(2) Go to Box 27
Healthy term infant with jaundice not clinicallysignificant by medical judgment
Follow infant in routine clinical supervision
1617
18 19
20
21
(Go to Box 22)
Yes
Yes
No
No
Is jaundicepersisting
gt 2 weeks
Does this infant haveabnormal physicalexam results dark
urine or light stools
Is jaundice persistinggt 3 weeks
Perform appropriate physical andlaboratory assessment of theinfant including possibility of
cholestatic jaundice
Provide routine carerecommend routine
feeding and follow-up Table 2 Management of Hyperbilirubinemia in the Healthy Term NewbornAgehours TSB Level mgdL (umolL)
Consider Phototherapy Exchange ExchangePhototherapy Transfusion Transfusion
if Intensive and IntensivePhototherapy PhototherapyFails
lt24 25-48 gt 12 (170) gt15 (260) gt 20 (340) gt 25 (430)49-72 gt 15 (260) gt 18 (310) gt 25 (430) gt 30 (510)gt 72 gt 17 (290) gt 20 (340) gt 25 (430) gt 30 (510)
TSB indicates total serum bilirubinPhototherapy at these TSB levels is a clinical option meaning that the intervention is availableand may be used on the basis of individual clinical judgement For a more detailed descriptionof phototherapy see the AppendixIntensive phototherapy (Appendix) should produce a decline of TSB of 1 to 2 mgdL within 4 to 6hours and the TSB level should continue to fall and remain below the threshold level for exchangetransfusion If this does not occur it is considered a failure of phototherapyTerm infants who are clinically jaundiced at lt 24 hours old are not considered healthy andrequire further evaluation (see text)
22 23
24
25
26
YesYes
No
YesNo
No 27
Algorithm Management of hyperbilirubinemia inthe healthy term infant
(From Box 19)
Jaundice in the Healthy Term Newborn
April 2002 Page 19 of 20
AlgorithmPediatric clinician evaluatesterm newborn with jaundice
Does the infant have signs of underlyingserious illness (lethargy apnea tachypneatemperature instability behavior changeshepatosplenomegaly persistant vomiting
or persistent feeding difficulty)
1
2
Exit this algorithm to individualizedclinical evaluation including
assessment of jaundice and underlyingdisease
Yes
3
No
Is the infant lt 37 weeks gestational age
4 Exit this algorithm to individualizedclinical evaluation including
assessment of jaundice in light ofprematurity
5
Yes
Is the mothersABO and Rh
blood typing andisoimmune
antibody screenstatus known
Is the mothersblood Rhpositive
Does themothers blood
have anyimmune
antibodies
Consider holding the infantscord blood in the blood bank incase future testing is necessary
6 7 8 9No
Yes Yes No
(Go to Box 10) (Go to Box 10) (Go to Box 10) (Go to Box 13)
No No Yes
Perform blood typing (ABO and Rh) and direct Coombs testingon the infants cord (preferably) or venous blood
10
Is the infantsblood direct
Coombs testpositive
Exit this algorithm to individualized clinical evaluationincluding assessment of jaundice and isoimmune
hemolytic disease
11 12
Yes
Are any of the following risk factors present tosuggest that nonisoimmune hemolytic disease
is possible in this infant(1) Family history of hemolytic anemia
OR(2) Family history of early or severe jaundice
OR(3) Ethnicity or geographic originassociated with hemolytic anemia
OR(4) Early or severe jaundice
Perform appropriate laboratoryassessment of infant including
(but not limited to consideration of)(1) Complete blood count differentialsmear reticulocyte count(2) G6PD screen(3) Hemoglobin electrophoresis
1314
No
No
No
(Go to Box 16)
Does the evaluation suggesthemolytic disease
15
Yes
(Go to Box 17)(Go to Box 16)
No
Jaundice in the Healthy Term Newborn
April 2002 Page 20 of 20
AlgorithmIs the infant
jaundiced andlt 24 hours of
age
Exit this algorithm to individualizedclinical evaluation includingassessment of jaundice and
nonisoimmune hemolytic disease
Is jaundiceclinicallysignificant by medical
judgment
(1) Measure infantstotal serum bilirubin(2) Go to Box 27
Healthy term infant with jaundice not clinicallysignificant by medical judgment
Follow infant in routine clinical supervision
1617
18 19
20
21
(Go to Box 22)
Yes
Yes
No
No
Is jaundicepersisting
gt 2 weeks
Does this infant haveabnormal physicalexam results dark
urine or light stools
Is jaundice persistinggt 3 weeks
Perform appropriate physical andlaboratory assessment of theinfant including possibility of
cholestatic jaundice
Provide routine carerecommend routine
feeding and follow-up Table 2 Management of Hyperbilirubinemia in the Healthy Term NewbornAgehours TSB Level mgdL (umolL)
Consider Phototherapy Exchange ExchangePhototherapy Transfusion Transfusion
if Intensive and IntensivePhototherapy PhototherapyFails
lt24 25-48 gt 12 (170) gt15 (260) gt 20 (340) gt 25 (430)49-72 gt 15 (260) gt 18 (310) gt 25 (430) gt 30 (510)gt 72 gt 17 (290) gt 20 (340) gt 25 (430) gt 30 (510)
TSB indicates total serum bilirubinPhototherapy at these TSB levels is a clinical option meaning that the intervention is availableand may be used on the basis of individual clinical judgement For a more detailed descriptionof phototherapy see the AppendixIntensive phototherapy (Appendix) should produce a decline of TSB of 1 to 2 mgdL within 4 to 6hours and the TSB level should continue to fall and remain below the threshold level for exchangetransfusion If this does not occur it is considered a failure of phototherapyTerm infants who are clinically jaundiced at lt 24 hours old are not considered healthy andrequire further evaluation (see text)
22 23
24
25
26
YesYes
No
YesNo
No 27
Algorithm Management of hyperbilirubinemia inthe healthy term infant
(From Box 19)
Jaundice in the Healthy Term Newborn
April 2002 Page 20 of 20
AlgorithmIs the infant
jaundiced andlt 24 hours of
age
Exit this algorithm to individualizedclinical evaluation includingassessment of jaundice and
nonisoimmune hemolytic disease
Is jaundiceclinicallysignificant by medical
judgment
(1) Measure infantstotal serum bilirubin(2) Go to Box 27
Healthy term infant with jaundice not clinicallysignificant by medical judgment
Follow infant in routine clinical supervision
1617
18 19
20
21
(Go to Box 22)
Yes
Yes
No
No
Is jaundicepersisting
gt 2 weeks
Does this infant haveabnormal physicalexam results dark
urine or light stools
Is jaundice persistinggt 3 weeks
Perform appropriate physical andlaboratory assessment of theinfant including possibility of
cholestatic jaundice
Provide routine carerecommend routine
feeding and follow-up Table 2 Management of Hyperbilirubinemia in the Healthy Term NewbornAgehours TSB Level mgdL (umolL)
Consider Phototherapy Exchange ExchangePhototherapy Transfusion Transfusion
if Intensive and IntensivePhototherapy PhototherapyFails
lt24 25-48 gt 12 (170) gt15 (260) gt 20 (340) gt 25 (430)49-72 gt 15 (260) gt 18 (310) gt 25 (430) gt 30 (510)gt 72 gt 17 (290) gt 20 (340) gt 25 (430) gt 30 (510)
TSB indicates total serum bilirubinPhototherapy at these TSB levels is a clinical option meaning that the intervention is availableand may be used on the basis of individual clinical judgement For a more detailed descriptionof phototherapy see the AppendixIntensive phototherapy (Appendix) should produce a decline of TSB of 1 to 2 mgdL within 4 to 6hours and the TSB level should continue to fall and remain below the threshold level for exchangetransfusion If this does not occur it is considered a failure of phototherapyTerm infants who are clinically jaundiced at lt 24 hours old are not considered healthy andrequire further evaluation (see text)
22 23
24
25
26
YesYes
No
YesNo
No 27
Algorithm Management of hyperbilirubinemia inthe healthy term infant
(From Box 19)