NEONATAL JAUNDICE

FACULTY OF MEDICINE TRISAKTY UNIVERSITY

JAKARTA, JUNE 2011

Name: Ayuniza Harmayati

Student Number: 030.08.051

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PREFACE

Assalamu’alaikum Wr Wb,

I would like to thank God for his blessing all though my works so I could finish this paper in

time. This paper would not been possible without the continued interest and enthusiasm of my family,

my incredible friends and so many lecturer whom most grateful.

Thanks to lecturer Prof. dr. Muzief Munir, SpA (K) for her guidance and help on this paper.

This paper titled “Neonatal Jaundice” that I arranged in order to complete my English assignment for

subject Medical English 3rd in the Faculty of Medicine Trisakti University. And thanks to my friends

for their helps, without their helps and support I would not be able to finish this paper.

I apologize for all mistakes that I made in this paper. I hope this paper could be useful for its

reader.

Jakarta, June 2011

Ayuniza Harmayati

030.08.051

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CONTENT

Preface 1

Content 2

Abstract 3

Chapter I : Introduction 4

Chapter II : Discussion 5

Chapter III : Conclusion 16

Reference 17

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ABSTRACT

Jaundice is the most common reason for doing blood tests and starting therapy in

newborn infants. In some neonates serum bilirubin levels may become excessively high, and

in rare instances this may lead to brain damage (kernicterus). In such cases it is important to

start treatment quickly. We will discuss various approaches through which serum bilirubin

levels may be reduced, thus potentially preventing brain damage. Neonatal jaundice always

has a foundation in normal physiology. However, the degree of jaundice may be accentuated

by a number of pathological processes. These include hematomas and other occult

hemorrhage, AB0- and Rhesus incompatibility, and increased enterohepatic circulation of

bilirubin. In addition, genetic conditions such as galactosemia, hemolytic anemias, and

Gilbert and Crigler-Najjar syndromes can significantly increase jaundice in newborn infants.

Neonatal jaundice can be treated in several ways, including phototherapy, exchange

transfusion, breast milk substitutes, and drugs (e.g. intravenous immune globulin and

phenobarbital). By employing such therapies individually or in combination, it is possible to

achieve rapid reductions of dangerously high bilirubin levels, and thus reduce the risk of

sequelae. It is important to keep in mind that factors which may be unknown at the time of

discharge from hospital or birthing unit can contribute to significant increases in total serum

bilirubin levels after discharge. It is therefore important to evaluate an infant’s risk status

prior to discharge.

Key words: Newborn, jaundice, neonatal, therapy, phototherapy, pharmacology, intravenous

immune globulin

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CHAPTER I

INTRODUCTION

During the first week of life all newborns have increased bilirubin levels by adult

standards, with approximately 60% of term babies and 85% of preterm babies having visible

jaundice. Jaundice is the most common condition that requires medical attention in newborns.

The yellow coloration of the skin and sclera in newborns with jaundice is the result of

accumulation of unconjugated bilirubin. In most infants, unconjugated hyperbilirubinemia

reflects a normal transitional phenomenon. However, in some infants, serum bilirubin levels

may excessively rise, which can be cause for concern because unconjugated bilirubin is

neurotoxic and can cause death in newborns and lifelong neurologic sequelae in infants who

survive (kernicterus). For these reasons, the presence of neonatal jaundice frequently results

in diagnostic evaluation.

Incidence varies with ethnicity and geography. Incidence is higher in East Asians and

American Indians and lower in blacks. Kernicterus occurs in 1.5 of 100,000 births in the

United States. Death from physiologic neonatal jaundice per se should not occur. Death from

kernicterus may occur, particularly in countries with less developed medical care systems. In

one small study from rural Nigeria, 31% of infants with clinical jaundice tested had G-6-PD

deficiency, and 36% of the infants with G-6-PD deficiency died with presumed kernicterus

compared with only 3% of the infants with a normal G-6-PD screening test result.(7)

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CHAPTER II

DISCUSSION

JAUNDICE

Neonatal jaundice is jaundice that begins within the first few days after birth.

(Jaundice that is present at the time of birth suggests a more serious cause of the jaundice.) In

fact, bilirubin levels in the blood become elevated in almost all infants during the first few

days following birth, and jaundice occurs in more than half. For all but a few infants, the

elevation and jaundice represents a normal physiological phenomenon and does not cause

problems. (1)

Hyperbilirubinemia is a common and, in most cases, benign problem in neonates.

Nonetheless, untreated, severe indirect hyperbilirubinemia is potentially neurotoxic, and

conjugated-direct hyperbilirubinemia often signifies a serious hepatic or systemic illness.

Jaundice is observed during the 1st week of life in approximately 60% of term infants and

80% of preterm infants.

ETIOLOGY

A newborn infant's metabolism of bilirubin is in transition from the fetal stage, during

which the placenta is the principal route of elimination of the lipid-soluble bilirubin,to the

adult stage, during which the water-soluble conjugated form is excreted from hepatic cells

into the biliary system and then into the gastrointestinal tract. (2)

Unconjugated hyperbilirubinemia may be caused or increased by any factors :

increases the load of bilirubin to be metabolized by the liver (hemolytic anemias,

polycythemia, shortened red cell life as a result of immaturity or transfused cells, increased

enterohepatic circulation, infection), Damages or reduces the activity of the transferase

enzyme (genetic deficiency, hypoxia, infection, possibly hypothermia and thyroid

deficiency), Competes for or blocks the transferase enzyme (drugs and other substances

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requiring glucuronic acid conjugation for excretion), Leads to an absence or decreased

amounts of the enzyme or to reduction of bilirubin uptake by liver cells (genetic defect,

prematurity). (2)

PATHOPHYSIOLOGY

Bilirubin is largely formed by the destruction of red blood cells and the catabolism of

heme proteins. Heme is converted to biliverdin, which is converted to bilirubin by biliverdin

reductase. Bilirubin is transported to the liver, where it undergoes enzymatic-mediated

conversion from an insoluble unconjugated form to a water-soluble conjugate. The

conjugating enzyme is uridine diphosphate glucuronosyltransferase (UGT), which is

markedly diminished in the newborn infant. The soluble form of bilirubin is indirect reacting,

the-water soluble form direct reacting. After conjugation, bilirubin is excreted in the bile and

from there into the intestinal tract. In the intestinal tract, some of the conjugated bilirubin is

reconverted to the unconjugated variety by beta glucuronidase. This allows its reabsorption

into the enterohepatic circulation.(3)

At elevated levels, the unconjugated form is potentially neurotoxic in the newborn.

Bilirubin enters the brain if it is unbound to albumin, unconjugated, or if the blood-brain

barrier has been disrupted from a number of causes, including sepsis, acidosis, and

prematurity. The concentration of bilirubin in the brain and the duration of exposure are

important determinants of neurotoxicity.(3)

The newborn is especially vulnerable to hyperbilirubinemia for several reasons.

Increased hemolysis secondary to shortened red blood cell survival time or fetal-maternal

blood group incompatibility can result in increased formation of bilirubin. Impaired hepatic

uptake and inadequately developed enzymes delay its conjugation, and increased

enterohepatic circulation results in inefficient excretion. At any given time after birth, the

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serum bilirubin reflects a combination of bilirubin production, conjugation and enterohepatic

circulation.(3)

DIFFERENTIAL DIAGNOSIS

Jaundice, consisting of either indirect or direct bilirubin, that is present at birth or

appears within the 1st 24 hour of life requires immediate attention and may be due to

erythroblastosis fetalis, concealed hemorrhage, sepsis, or intrauterine infections, including

syphilis, cytomegalic inclusion disease, rubella, and congenital toxoplasmosis.(2)

Jaundice that first appears on the 2nd or 3rd day is usually “physiologic” but may

represent a more severe form. Jaundice that is noted initially after the 1st week of life

suggests breast milk jaundice, septicemia, congenital atresia or paucity of the bile ducts,

hepatitis, galactosemia hypothyroidism, CF, congenital hemolytic anemia (spherocytosis), or

hemolytic anemia related to drugs (as in congenital deficiencies of the enzymes glucose-6-

phosphate dehydrogenase [G6PD] or glutathione synthetase, reductase, or peroxidase).(2)

Low-risk jaundiced infants who are full term and asymptomatic may be evaluated by

monitoring serum total bilirubin levels. Regardless of the gestational age or time of

appearance of jaundice, those with significant hyperbilirubinemia and all patients with

symptoms or signs require a complete diagnostic evaluation, which should include

determination of the direct and indirect bilirubin fractions, hemoglobin, reticulocyte count,

and blood type, a Coombs test, and examination of a peripheral blood smear. Indirect-

reacting bilirubinemia, reticulocytosis, and a smear demonstrating evidence of red blood cell

destruction suggest hemolysis; in the absence of blood group incompatibility, non-

immunologically induced hemolysis should be considered. If direct-reacting

hyperbilirubinemia is present, hepatitis, congenital bile duct disorders (atresia, paucity, Byler

disease), cholestasis, inborn errors of metabolism, CF, and sepsis are diagnostic possibilities.

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If the reticulocyte count, Coombs test, and direct bilirubin are normal, physiologic or

pathologic indirect hyperbilirubinemia may be present.(2)

Physiologic Jaundice (Icterus Neonatorum)

The most common cause of unconjugated hyperbilirubinemia in the neonatal period is

physiologic jaundice. It is thought to result primarily from a six fold increase in bilirubin load

and a marked deficiency in uridine diphosphate glucurono-syltransferase (UGT) activity. In

addition, the hepatic uptake and excretion of bilirubin is transiently impaired.(3)

Under normal circumstances, the level of indirect-reacting bilirubin in umbilical cord

serum is 1–3 mg/dL and rises at a rate of less than 5 mg/dL/24 hour; thus, jaundice becomes

visible on the 2nd–3rd day, usually peaking between the 2nd and 4th days at 5–6 mg/dL and

decreasing to below 2mg/dL between the 5th and 7th days of life. Physiologic Jaundice is

believed to be the result of increased bilirubin production after the breakdown of fetal red

blood cells combined with transient limitation in the conjugation of bilirubin by the liver.(2)

In premature infants, jaundice both peaks and resolves somewhat later, and peak

levels can reach 12 mg/dL. Lower levels of bilirubin may be associated with kernicterus in

low-birth-weight, high-risk infants; therefore, any degree of jaundice in a premature infants

must be taken seriously. Physiologic jaundice is a non pathologic condition, with no

neurologic sequele. In premature infants, the rise in serum bilirubin tends to be the same or a

little slower than that in term infants, but it is of longer duration, which generally results in

higher levels, the peak being reached between the 4th and 7th days; the pattern depends on

the time required for the development of mature mechanisms for the metabolism and

excretion of bilirubin. (2)

The diagnosis of physiologic jaundice in term or preterm infants can be established

only by precluding known causes of jaundice on the basis of the history and clinical and

laboratory findings.(2)

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In general, a search to determine the cause of jaundice should be made if (2) :

1) it appears in the 1st 24–36 hour of life

2) serum bilirubin is rising at a rate faster than 0,5 mg/dL/24 hour

3) serum bilirubin is greater than 12 mg/dL in full-term (especially in the absence of risk

factors) or 10–14 mg/dL in preterm infants

4) Jaundice persists after 10–14 days of life

5) Direct-reacting bilirubin is greater than 2 mg/dL at any time.

Breast Milk Jaundice

In general, jaundice is more common in breast-fed infants than it is in bottle-fed

infants. The early –onset jaundice is referred to as breast-feeding jaundice, which is akin to a

relative starvation state, putting infants at risk for dehydration and increased enterohepatic

reuptake of bilirubin. Effective early lactation is the key to its prevention. Breast milk

jaundice typically occurs after the first 3 or 5 days of life and can persist for several weeks to

a few months. This may be due in part to substances contained in breast milk that antagonize

the conjugation and excretion of bilirubin. Rarely, breast-fed infants can develop elevation of

unconjugated bilirubin starting in the first week of life, which can reach 15 to 27 mg per 100

ml by the second or third week. The hyperbilirubinemia resolves with the cessation of breast

feeding and does not recommended in all infants, but rather is reserved for infants with

bilirubin levels that place the newborn at risk for kernicterus. A diagnosis of breast milk

jaundice assumes that other pathologic causes of hyperbilirubinemia have been considered

and eliminated. It is important to note that although 50 % of breast-fed infants develop

jaundice, less than 1% develop bilirubin levels that are of concern.(3)

Pathologic Hyperbilirubinemia

Jaundice and its underlying hyperbilirubinemia are considered pathologic if their time

of appearance, duration, or pattern of serially determined serum bilirubin concentrations

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varies significantly from that of physiologic jaundice or if the course is compatible with

physiologic jaundice but other reasons exist to suspect that the infant is at special risk from

the neurotoxicity of unconjugated bilirubin. The combination of G6PD deficiency and a

mutation of the promoter region of UDP-glucuronyl transferase 1 produce indirect

hyperbilirubinemia in the absence of signs of hemolysis. Nonphysiologic hyperbilirubinemia

may also be caused by mutations in the gene for bilirubin UDP-glucuronyl transferase.(2)

Hemolytic disease of the newborn may be secondary to ABO or Rh incompatibilities.

When the incompatibility results from the Rh antigen, the condition is more serious and

without treatment may result in erythroblastosis fetalis or death. ABO problems occur much

more frequently but are less serious. Both result from RBCs from the fetus passing into the

mother’s circulation and when different from the mother’s, maternal production of antibodies

against the fetal RBCs.(4)

ABO incompatibility occurs in about 20 % of pregnancies. Almost half the American

population has O+ blood, which contains both anti-A and anti-B antibodies. The manner in

which these antibodies are produced from RBCs without A and B antigens is unknown. The

second most common blood type, A, occurs in 40 % of the population and contains

antibodies to b. Blood type B occurs in 11 % of the population and has anti-A antibodies; the

last common blood type, AB, occurs in only 4 % of the population and is without either

antibody. It is thought that these antibodies are weaker than the Rh ones and therefore, may

persist for as long as 3 months, but it does not usually cause kernicterus. The bilirubin

generally stays below 15 mg/dL, except in a rare condition, the lucey-driscoll syndrome,

which may occur in the first few days and is associated with high levels of indirect

bilirubinemia and kernicterus.(4)

Direct bilirubinemia usually develops in newborns 2 weeks of age or older. This type

of jaundice may result from problems within the liver as well as extra hepatic ones. The most

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common intrahepatic causes include neonatal hepatitis or viral hepatitis. Most of the cases of

neonatal hepatitis (50 % - 60 %) are unrecognized, and the second most common cause are

the pathogens responsible for infections in newborns : TORCH, hepatitis B virus, varicella,

adenovirus and other infection agents. (4)

TREATMENT

The clinical course in most cases of neonatal jaundice defines the problem as benign

and self-limited. Unless the infant has clear evidence of a hemolytic anemia or some other

significant perinatal or postnatal abnormality, most cases of “physiologic hyperbilirubinemia”

can be managed with observation, serial bilirubin measurements, and reassurance. Despite an

extensive differential diagnosis for neonatal jaundice, the majority of cases are attributable to

a small number of causes that are usually detectable by serial bilirubin determinations,

examination of the patient, and review of maternal and neonatal blood type and antibody

studies.(5)

Pharmacologic agents

Pharmacologic agents have been used in the management of hyperbilirubinemia to

stimulate the induction of hepatic enzymes and carrier proteins, to interfere with heme

degradation, or to bind bilirubin in the intestines to decrease enterohepatic reabsorption.

Intravenous immunoglobulin has been used with infants with severe Rh and ABO

incompatibility to suppress isoimmune hemolysis and decrease the number of exchange

transfusion.(6)

PHOTOTHERAPY

Clinical jaundice and indirect hyperbilirubinemia are reduced on exposure to a high

intensity of light in the visible spectrum. Bilirubin absorbs light maximally in the blue range

(420–470 nm). Nonetheless, broad-spectrum white, blue, special narrow-spectrum (super)

blue, and less often, green lights have been effective in reducing bilirubin levels. Bilirubin in

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the skin absorbs light energy, which by photo-isomerization converts the toxic native

unconjugated 4Z,15Z-bilirubin into the unconjugated configurational isomer 4Z,15E-

bilirubin. The latter is the product of a reversible reaction and is excreted in bile without any

need for conjugation. Phototherapy also converts native bilirubin, by an irreversible reaction,

to the structural isomer lumirubin, which is excreted by the kidneys in the unconjugated state.

(2)

Phototherapy is indicated only after the presence of pathologic hyperbilirubinemia has

been established. The basic cause or causes of the jaundice should be treated concomitantly.

Prophylactic phototherapy in very low birth weight (VLBW) infants may prevent

hyperbilirubinemia and may reduce the incidence of exchange transfusions. VLBW infants

receiving phototherapy for 1–3 days have peak serum bilirubin concentrations about half

those of untreated infants. In premature infants without significant hemolysis, serum bilirubin

usually declines 1–3 mg/dL after 12–24 hour of conventional phototherapy, and peak levels

may be decreased by 3–6 mg/dL. The therapeutic effect depends on the light energy emitted

in the effective range of wavelengths, the distance between the lights and the infant, and the

amount of skin exposed, as well as the rate of hemolysis and in vivo metabolism and

excretion of bilirubin. The commercial phototherapy units available vary considerably in

spectral output and the intensity of radiation emitted; therefore, the dose can be accurately

measured only at the skin surface. Dark skin does not reduce the efficacy of phototherapy.(2)

Conventional phototherapy is applied continuously, and the infant is turned frequently

for maximal skin exposure. It should be discontinued as soon as the indirect bilirubin

concentration has been reduced to levels considered safe in view of the infant's age and

condition. Serum bilirubin levels and hematocrit should be monitored every 4–8 hour in

infants with hemolytic disease or those with bilirubin levels near the range considered toxic

for the individual infant. Others, particularly older infants, may be monitored at 12–24 hour

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intervals. Monitoring should continue for at least 24 hour after cessation of phototherapy in

patients with hemolytic disease because unexpected rises in serum bilirubin sometimes occur

and require further treatment. Skin color cannot be relied on for evaluating the effectiveness

of phototherapy; the skin of babies exposed to light may appear to be almost without jaundice

in the presence of marked hyperbilirubinemia.(2)

The infant's eyes should be closed and adequately covered to prevent exposure to

light. Excessive pressure from an eye bandage may injure the closed eyes, or the corneas may

be excoriated if the eyes can be opened under the bandage. Body temperature should be

monitored, and the infant should be shielded from bulb breakage. If feasible, irradiance

should be measured directly and details of the exposure recorded (type and age of the bulbs,

duration of exposure, distance from the light source to the infant, and so forth). In infants

with hemolytic disease, care must be taken to not overlook developing anemia, which may

require transfusion.(2)

Complications of phototherapy include loose stools, erythematous macular rash, a

purpuric rash associated with transient porphyrinemia, overheating and dehydration

(increased insensible water loss, diarrhea), chilling from exposure of the infant, and bronze

baby syndrome. Phototherapy is contraindicated in the presence of porphyria. Eye injury and

nasal occlusion from the bandages are uncommon.(2)

Wide clinical experience suggests that long-term adverse biologic effects of

phototherapy are absent, minimal, or unrecognized. However, those using phototherapy

should remain alert to these possibilities and avoid any unnecessary use because untoward

effects on DNA have been demonstrated in vitro.(2)

EXCHANGE TRANSFUSION

Exchange transfusion is performed if intensive phototherapy has failed to reduce

bilirubin levels to a safe range and if the risk of kernicterus exceeds the risk of the procedure

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or the infant has signs of kernicterus. Potential complications from exchange transfusion are

not trivial and include acidosis, electrolyte abnormalities, hypoglycemia, thrombocytopenia,

volume overload, arrhythmias, NEC, infection and death.(2)

Various factors may affect the decision to perform an exchange transfusion in an

individual patient. The appearance of clinical signs suggesting kernicterus is an indication for

exchange transfusion at any level of serum bilirubin. A healthy full-term infant with

physiologic or breast milk jaundice may tolerate a concentration slightly higher than 25

mg/dL with no apparent ill effect, whereas kernicterus may develop in a sick premature infant

at a significantly lower level. A level approaching that considered critical for the individual

infant may be an indication for exchange transfusion during the 1st day or two of life when a

further rise is anticipated, but not on the 4th day in term infants or on the 7th day in

premature infants, when an imminent fall may be anticipated as the hepatic conjugating

mechanism becomes more effective.(2)

Tabel : Treatment of Jaundice based on Bilirubin Total

AGEPHOTOTHERAPY EXCHANGE TRANSFUSION

Health infant Risk factor Health infant Risk factormg/dL µmol/L mg/dL µmol/L mg/dL µmol/L mg/dL µmol/L

1st day All visible icterus 15 260 13 2202nd day 15 260 13 220 25 425 15 2603rd day 18 310 16 270 30 510 20 340> 4th day 20 340 17 290 30 510 20 340

COMPLICATIONS

Acute bilirubin encephalopathy. Bilirubin is toxic to cells of the brain. If a baby has severe

jaundice, there's a risk of bilirubin passing into the brain, a condition called acute bilirubin

encephalopathy. Prompt treatment may prevent significant permanent damage. The following

signs may indicate acute bilirubin encephalopathy in a baby with jaundice such as listless,

sick or difficult to wake, high-pitched crying, poor sucking or feeding, backward arching of

the neck and body, fever and vomiting. (8)

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Kernicterus. Kernicterus is the syndrome that occurs if acute bilirubin encephalopathy

causes permanent damage to the brain. Kernicterus may result in involuntary and

uncontrolled movements (athetoid cerebral palsy), permanent upward gaze, hearing loss,

intellectual impairment.(8)

PREVENTION

Prevention has focused on early initiation of feedings and frequent breastfeeding to decrease

enterohepatic shunting, promote establishment of normal bacterial flora and stimulate

intestinal activity.(6) Encourage all mothers to breastfeed their babies 8 - 12 times a day in the

first 2 - 3 days of life. Test all pregnant women for ABO, Rh (D) blood types and red cell

antibodies, during pregnancy. If the mother has red blood cell antibodies noted antenatally

then send cord blood for blood group including Rhesus type, direct antibody test (DAT) also

known as Coombs test, FBC for haemoglobin and haematoctrit, total serum bilirubin and

albumin. Encourage the ingestion of colostrum to increase stooling which prevents

reabsorption of bilirubin. Educate parents regarding signs of adequate hydration, feeding and

signs of jaundice. (9)

PROGNOSIS

Prognosis is excellent if the patient receives treatment according to accepted guidelines.

Brain damage due to kernicterus remains a true risk, and the apparent increased incidence of

kernicterus in recent years may be due to the misconception that jaundice in the healthy full

term infant is not dangerous and can be disregarded. (7)

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CHAPTER II

CONCLUSION

Most jaundice in newborn babies is a normal event and is not serious. In most cases,

this jaundice will disappear after a few days, often without any special treatment. Also, once

this type of jaundice disappears, there is no evidence that it will appear again or that it has

any lasting effects on the baby. Premature infants are more likely to develop jaundice than

full-term babies.

Extreme jaundice requires emergency intervention in order to prevent lasting

neurological damage. The first step is always phototherapy, which can be expected to be

more effective the higher the total serum bilirubin, and will result in biliary and urinary

excretion of polar bilirubin isomers. A breast milk substitute should probably be given

routinely in extreme jaundice, as long as there are no direct contraindications to enteral

nutrition. This will reduce enterohepatic circulation. The family and case histories need to be

explored for hereditary or metabolic conditions which increase the risk of hyperbilirubinemia

(hemolytic anemias, Gilbert syndrome, Crigler-Najjar syndrome, galactos-emia).

Parents should be educated about neonatal jaundice and receive written information

prior to discharge from the birth hospital. The parent information leaflet should preferably be

available in several languages. Prognosis Dependent on the underlying cause, but otherwise

excellent with prompt diagnosis and treatment.

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Reference

1. __________________. Jaundice. Available at :

http://www.medicinenet.com/jaundice/discussion-100.htm. Accessed June 9, 2011

2. Stoll B. J, Kliegman R. M. Digestive System Disorder – Jaundice and

Hyperbilirubinemia in newborn. In : Behrman, Kliegman, Jenson. Nelson Textbook of

Pediatrics 17th edition. Elsevier - Health Sciences Division; 2007. p. 593-599

3. Singh A, Abrens W.R. Jaundice. In : Strange G. R, Ahrens W. R, Schafermeyer R. W.

Pediatric Emergency Medicine: Third Edition. USA; McGraw-Hill Companies; 2009.

p. 85-89

4. Muma R.D. Neonatal Jaundice. In : Patient education: a practical approach. Library of

congress cataloging-in-publication data; 1996. p. 233

5. Cashore W.J. Neonatal Hyberbilirubinemia. In : McMillan J.A, Feigin R.D,

DeAngelis C. Oski's pediatrics: principles & practice third edition. Philadelphia;

Lippincott Williams & Walkins; 2006. p. 235-248

6. Bilirubin Metabolism. In : Blackburn S. T . Maternal, fetal, & neonatal physiology: a

clinical perspective third edition. USA; Saunders Elsevier; 2007. p. 654-656

7. Hansen T.W.R. Neonatal Jaundice [ 7 January 2011]. Available at :

http://emedicine.medscape.com/article/974786-overview. Accessed June 9, 2011

8. Mayo Clinic Staff. Infant Jaundice. Available at :

http://www.mayoclinic.com/health/infant-jaundice/DS00107. Accessed June 9, 2011

9. Statewide Maternity and Neonatal Clinical Guidelines Program. Neonatal jaundice:

prevention, assessment and management. Available at :

http://www.health.qld.gov.au/cpic/resources/mat_guidelines.asp. Accessed June 10,

2011

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