HO SIEW CHOK HUI

DefinitionYellow discolouration of the

skin ,sclerae or mucous membrane due to elevation of serum bilirubin

It is usually become mores apparent at a total serum bilirubin level of 5 mg/dl

Jaundice is observed during the 1st wk

in approximately 60% of term infant

and 80% of preterm infant.

Hyperbilirubinemia can be toxic, with

high levels resulting in an

encephalopathy known as kerni-cterus

Increased production in neonate due to larger red cell volume, which produces bilirubin as cells are broken down and shorter RBC life span, so broken down faster.

Heme is catabolized within the reticuloendothelial system by heme oxygenase to form biliverdin.

Biliverdin is metabolized to bilirubin in the presence of biliverdin reductase

Ligandins responsible for transport from plasma membrane to endoplasmic reticulum.

Bilirubin conjugated in presence of UDPGT (uridine diphosphate glucuronyl transferase) to mono and diglucoronides, which are then excreted into bile canaliculi.

Benign Physiologic Breast Milk Breastfeeding

Pathologic Many causes

Icterus neonatorum (physiology jaundice)The most common form of indirect jaundice

in infants under 14 days of age between 24-72 hours of age, peaks by 4-5 days in term and 7th day in

preterm neonates and disappears by 10-14days of life.

It is predominantly unconjugated and levels usually do not exceed 15 mg/dl.

caused by increased bilirubin production with transient limited conjugation abilities

Increased rbc’s

Shortened rbc lifespan

Immature hepatic uptake & conjugation

Increased enterohepaticCirculation

Breast Milk jaundice develops after the first 4-7 days of life

Increased enterohepatic circulation of bilirubin due to (1) increased content of beta glucuronidase activity in breast

A diagnosis of breast milk jaundice should be considered if the serum bilirubin is predominantly unconjugated, other causes of prolonged jaundice have been excluded and the infant is in good health, vigorous and feeding well and gaining weight adequately

Breast feeding jaundice Occures in the first week of life and is

caused by insufficient production or intake of breast milk.

Jaundice in breast-fed babies usually appearsbetween 24-72 hours of age, peaks by 5-15 days of life and disappears by the third weekof life.

Pathologic jaundice Appearance of jaundice within 24 hours, increase in serum bilirubin beyond 5

mg/dl/day, peak levels above the expected normal

range, presence of clinical jaundice beyond 2

weeks and conjugated bilirubin (dark urine staining the clothes)

Features Jaundice in 1st 24 hrs Rapidly rising TSB (> 5

mg/dL per day) TSB > 17 mg/dL

Categories Increased bilirubin load Decreased conjugation Impaired bilirubin

excretion

Hemolytic Disease Features: elevated reticulocytes,

decreased Hgb Coomb’s + Rh incompatibility, ABO

incompatibility, minor antigens Coomb’s - G6PD, spherocytosis,

pyrovate kinase deficiency

Non-hemolytic Disease normal reticulocytes Extravascular sources – I.e.

cephalohematoma Polycythemia Exaggerated enterohepatic circulation –

I.e. CF, GI obstruction

Elevated unconjugated bilirubinGenetic Disorders

Crigler-Najjar▪ 2 types▪ Severe hyperbilirubinemia

Gilbert Syndrome▪ Mild hyperbilirubinemia

Hypothyroidism

Crigler-Najjar syndrome is elicited by a lack or deficiency of the enzyme uridine diphosphate glycosyltransferase (UGT).

Type 1 Crigler-Najjar syndrome is associated with an almost complete absence of the enzyme, which results in very high levels of unconjugated hyperbilirubinemia (up to 50 mg/dL) at birth.

Lower levels of serum bilirubin (up to 20 mg/dL) and markedly depressed activity of hepatic UGT are characteristic of type 2 Crigler-Najjar syndrome

Elevated unconjugated and conjugated bilirubin (> 2 mg/dL or > 20% of TSB)

Biliary Obstruction Structural defects – I.e. biliary atresia Genetic defects – Rotor’s & Dubin-Johnson

syndromes Infection – sepsis, TORCH Metabolic Disorders – I.e. alpha1 antitrypsin

deficiency Chromosomal Abnormalities – Turner’s

syndrome Drugs – I.e. ASA, sulfa, erythromycin

Prolonged jaundiceCauses1)Unconjugated HyperbilirubinemiaHypothyroidismHaemolysis (G6PD/ cogenital

spherocytosis)GalactosemiaGilbert syndromeSepsis / UTIBreast milk Jaundice

Conjugated hyperbilirubinemiaBiliary tree abnormalitiesBiliary atresiaCholedochal cystPaucity of bile ducts (Alagille syndrome )Idiopathic neonatal hepatits syndromeTORCHESMetabolic disease (Citrin

deficiency,galactosemia , PFIC , alpha1 antitrypsin deficiency )

TPNSepsis / UTI

ASPHYXIA TRAUMA Metabolic disorder (acidosis ,

hypoglycemia) Sepsis Prematurity Intestinal obstruction Enzyme deficiency : G6PD deficiency Hypothyroidism

Close surveillance of these patient will ensure of early detection of severe jaundice and effective treatment

Jaundice below umbilicus, corresponding to serum bilirubin of 12-15 mg/dl (200-250 mmol/L).

Jaundice up to level of the sole of the feet - likely to need exchange transfusion.

Jaundice within 24 hours of life. Rapid rise of serum bilirubin of more than 8.5

mmol/L/hour (>0.5 mg/dl/hour). Prolonged jaundice of more than 14 days - other

causes/conditions need to be excluded e.g. neonatal hepatitis, biliary atresia.

Family history of significant haemolytic disease or kernicterus

Clinical symptoms/signs suggestive of other diseases e.g. sepsis.

Prenatal/Perinatal : Pregnancy complications Gestation age Maternal blood type/Rh Infections Drug use Delivery method/Delivery intervention Birth weight Previous miscarriages Previous infants with NNJ, kernicterus,

neonatal death, G6PD deficiency

HPI Onset of jaundice Rate of progress of jaundice Appropriate weight gain Trauma Evidence of bleeding /bruising Presence of symptoms such as

apnoea, difficulty in feeding, feed intolerance

and temperature instability.

Diet history :Breast and /or formula fed , length of

time on each breast. Latch strength

Family history :Bleeding disorder, perinatal deaths ,

endocrinopathies

General condition–whether ill-looking or lethargic, presence of hypotonia, or

abdominal distension.Level of jaundicePallor? Cephalohaematoma/subaponeurotic

haematoma,

Look for signs of sepsisPresence of lethargy, poor feeding, failure to thrive, hepato-splenomegaly, temperature

instability or apnea may be a marker of an underlying serious disease.

Look for signs of intrauterine infection –rashes ,Hepatosplenomegaly , SGA

Look for any signs of kernicterus

When a neonate is jaundiced, the yellow discoloration of skin first appears on the face

and it progresses to the trunk, to the palm of the hand, and then the sole of the feet-ie cephalo-caudal progression.

The intensity of yellow discoloration correspondingly increases from the face caudally as the severity of jaundice increases.

Jaundice can be detected by blanching the skin of the neonate with digital pressure exposing the colour of the underlying skin.

The severity of neonatal jaundice is assessed clinically using Kramer’s chart based on dermal zones of neonatal jaundice, where the levels of serum bilirubin correlate with the area of skin that is jaundiced, as indicated in the table

This is applicable to full term infants with jaundice not due to all hemolytic conditions

included Rh incompatibility.

Zone 1 2 3 4 5

SB(umol/L)

100 150 200 250 >250

Kramer drew attention to the observation that jaundice starts on the head, and extends towards the feet as the level rises. This is useful in deciding whether or not a baby needs to have the SB measured. Kramer divided the infant into 5 zones, the SBR range associated with progression to the zones is as follows:

Table 1: correlation between levels of serum bilirubin with the area of skin that is Jaundiced

Area of body Range of indirect bilirubin mg/dl(mmol/L)

Head & neck 4-8 (68-135) Upper trunk 5-12 (85-204) Lower trunk and thigh 8-16 (136-272) Arms & lower legs 11-18 (187-306) Palms and soles >18 (>306)

(NB: It may be difficult to assess jaundice in dark skinned infants).

Principles :Do TSB stat. Estimates of TSB based solely on clinical examination are not reliable

Admit & investigate :Babies who are UNWELL regardless of the TSB levelBabies with jaundice onset< 24 hrs of lifeBabies requiring phototherapy

Total serum bilirubin - sufficient in most cases Unconjugated & conjugated fractions in

specific conditions eg prolonged NNJ Infant’s blood group, maternal blood group Direct Coomb’s test G6PD status (if not already known) Full blood count Reticulocyte count Peripheral blood film (if hereditary

spherocytosis suspected) Blood culture, Urine microscopy and culture

(if infection is suspected)

Copyright ©2004 American Academy of Pediatrics

Subcommittee on Hyperbilirubinemia, Pediatrics 2004;114:297-316

Nomogram for designation of risk in 2840 well newborns at 36 or more weeks' gestational age with birth weight of 2000 g or more or 35 or more weeks' gestational age and birth weight of 2500 g or more based on the hour-specific serum bilirubin

values

Copyright ©2004 American Academy of Pediatrics

Subcommittee on Hyperbilirubinemia, Pediatrics 2004;114:297-316

Algorithm for the management of jaundice in the newborn nursery

Copyright ©2004 American Academy of Pediatrics

Subcommittee on Hyperbilirubinemia, Pediatrics 2004;114:297-316

Guidelines for phototherapy in hospitalized infants of 35 or more weeks' gestation

Advise for physiological jaundice: The parents should be explained about

the benign nature of jaundice. Encourage more frequent

breastfeeding to stimulate the gut and hence increase excretion of bilirubin via the stool

DO NOT encourage or allow supplementary fluids like glucose or water as it will prolong the jaundice.

Pathologic jaundice baby’s blood group, Rh typing and DCT

(if mother is Rh negative or O group);FBC

packed cell volume (PCV); peripheral blood smear (PBS) for hemolysis and red blood cell morphology; reticulocyte count ; RP ; LFT

Do TSB 6 hrly Phototherapy / ET

If a child has near exchange transfusion or higher TSB level but no signs of kernicterus and is well :

Prepare for exchange transfusion Double phototherapy Put up an IV line and maintainence

fluids Continue breastfeeding Rpt SB at 4 hrs If SB cont’ to rise , proceed with ET

Prolonged jaundice beyond 2 weeks: The common causes include breast milk jaundice,

extravasated blood (cephalhematoma), hemolytic disease, G-6PD deficiency and hypothyroidism.

One should rule out cholestasis by noting the urine color and checking the level of direct bilirubin.

Investigations to rule out cholestasis (stool color, urine color, direct and indirect bilirubin levels)

Investigations to rule out ongoing hemolysis, G-6PD screen

Investigations to rule out hypothyroidism Investigations to rule out urinary tract infection.

InvestigationFBC , PBFRP , LFTHep B, Hep C screenTORCHES Urine Feme and C+SUrine reducing sugar , Ferric chlorideG6PD status , TFTMother & baby blood groupCoombs test

If unconjugated hyperbilirubinemiaAdmit if patient is unwellInvestigationExclude UTI and hypothyrodismBreast milk jaundice is diagnosis of

exclusionChild must be well, ,gaining weight

appropriately ,breastfeed well and stool is yellow

Management is continue breast feeding

If conjugated hyperbilirubinaemiaAdmit and observe colour of stool for 3

consecutive daysStart phenobarbitone on admission at

5mg/kg OD for 5 days to prime the liver for HIDA scan if eventually required

Further IX : LFT , Hep B &C status, TORCHES ,VDRL test , alfa-1 antitrypsin and IEM screen

Consider Alagille syndrome

Alagille syndrome is an autosomal dominant disorder with variable expression.

Associated abnormalities include those of the liver, heart, eye, skeleton, and kidneys and characteristic facial features.

Mild-to-moderate mental retardation also may be present.

Typical facial features of Alagille syndrome. Note broad forehead, deep-set eyes and pointed chin

If the stool is pale over 3 consecutive days, suspect biliary atresia and inform Paediatric surgeon and plan for

1)US of liver2)HIDA scan3)Liver biopsy4)Operative cholangiogram

US of hepatobiliary system- Done after4 hrs of fasting- Dilated intrahepatic bile ducts and

absent gall bladder – raises the suspicious of extrahepatic biliary atresia

HIDA scan after 5 days of phenobarbitone

-Low uptake with normal excretion : neonatal hepatitis syndrome- Normal uptake with absent excretion

: Extrahepatic biliary atresia

Liver biopsy- Ensure PT and APTT normal- If not give Vit K 1 mg IV- Platlet count > 40,000

Biliary atresia -Kasai procedure -must be performed within 2 months of life

Neonatal Hepatitis Syndrome- Followup with LFT fortnightly- Watch out for liver failure and

bleeding tendency (Vit K deficiency)- Repeat Hep B and C screening at 6

weeks- Most infants with neonatal hepatitis

made a complete recovery

To prevent potentially dangerous bilirubin levels

and to decrease the need for exchange transfusion, since phototherapy changes bilirubin into more soluble forms to be excreted in the bile or urine (lumirubin )

The minimum irradiance is 6-12 μW/cm2/nm the distance of the light source from the

baby, the optimum distance being 35 - 50 cm

Expose infant appropriately Baby must be completely naked for full

exposure Eye must be covered Beware of hypo/hyperthermia Ensure adequate hydration Turn off photolights during feeding /blood

taking

COMPLICATIONS Tanning and bronze baby Diarrhea Skin rash or burns Dehydration Haemolysis Hyperthermia/ hypothermia

Purpose1)To lower the SB level and reduce

risk of kernicterus2)To remove the infant’s sensitised

RBC and the circulating ab and reduce the degree of red cell destruction

3)To control the blood volume and relieve potential heart failure

Blood vol to exchange 160ml/kg body weight 1 ml of 4.2 % NaHCo3 given for every 100mls

of blood exchanged 1 ml of 10% calcium gluconate given for

every 160mls of blood exchanged Rate of exchange 3min /cycle and total

exchange should be about 90 min Exchange start with removal of blood If child anaemic (hb< 15) ,give an extra

aliquot vol of blood at the end , leaving +ve balance

Always discard the serum & last portion of blood in the tube to avoid electrolyte imbalance

Feed after3 hrs If initial SB is 25mg % , do not remove the

UVC as ET may need to be repeated

IxPre exchange (1st vol of blood removal ) Blood C+S TSB VDRL , HIV ,Hep B and Hep C screening DCT , HbPost exchange (last vol of blood removed ) TSB FBC blood sugar BUSE, calcium

4- 6 hour post exchange : TSB

Complication

Catheter relatedInfection, Haemorrhage, NEC , Air embolism ,Portal and splenic vein thrombosis

Haemodynamic problemsOverload cardiac failurehypovolemic shockArrhythmia

Electrolyte imbalanceHyperkalemia , hypocalcemiahyper/hypo-glycemiametabolic acidosis / alkalosis

FollowupReview TSB at nearest PKK 2 days

after d/cFollowup for 2 years and d/c if

normalLook for signs of deafness , cerebral

palsy and mental retardationFor hearing and neurodevelopmental

assessment

Management of jaundice in healthy newborns , MOH Clinical practice guidelines

Paediatric Protocol for Hospital in SarawakThird edition

Paediatric Protocols for Malaysian Hospital 2nd edition 2008

American Academy of Pediatrics, Subcommittee on Hyperbilirubinemia. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation