1. Jaundice – neonatal, prolonged and beyond
Dr. KW So
Department of Paediatrics
The Chinese University of Hong Kong

2. Jaundice
Clinical diagnosis – yellow discoloration of skin due to hyperbilirubinemia
Commonest reason for admission in the neonatal unit
During neonatal period, most are benign but may cause irreversible brain damage
Beyond neonatal period, all have underlying causes

3. Classification Pre-hepatic Hepatic Post-hepatic
(Increase bilirubin load)
Increase breakdown of hemoglobin
Hepatic
(Reduce conjugation or excretion)
Reduce uridine diphosphate glucuronosyltransferase (UDPGT) activity
Hepatocellular dysfunction
Post-hepatic
(Reduce excretion outside the liver or increase reabsorption)
Biliary tract obstruction
Increase enterohepatic circulation

4. Diagnosis of Jaundice Clinical examination
Sclera Vs Skin
Transcutaneous bilirubinometer
Serum bilirubin

5. Early Neonatal Jaundice
Within 48 hour after delivery
Common or important causes:
Hemolysis
Blood group incompatibility
G6PD deficiency
Poor feeding / dehydration
Infection

6. Blood group incompatibility
ABO group incompatibility
Commonest cause of early neonatal jaundice in HK
Blood group A or B baby of group O mother
Rhesus Incompatibility
Rhesus +ve baby of sensitized Rhesus –ve mother
Minor blood group incompatibility

7. ABO Incompatibility Early onset jaundice – within 24 hour after birth
Baby blood group A or B, Mother blood group O
Direct Coomb’s test +ve
Blood smear show increase spherocytes
Usually can be controlled with phototherapy

8. Glucose-6-phosphate dehydrogenase deficiency
Incidence: male 4.4%, female 0.35% in HK
Essential for the converting oxidized haemoglobin back to haemoglobin
Oxidized Hb
GSH
NADP
G6P
G6PD
6GP Hb
GSSH
NADPH

9. G6PD deficiency Early or prolonged jaundice
Acute severe jaundice with precipitating factors
Massive intravascular haemolysis => free haemoglobin in urine (urine haemstix +ve but no red cell seen under microscopy)
Prone to bilirubin encephalopathy
May complicate with acute renal failure

10. Approach to Early Neonatal Jaundice
History
Age of onset
General well being
Maternal blood group
Screening result & family history of G6PD deficiency
Type & amount of feeding
Urine output & color
Body weight change

11. Approach to Early Neonatal Jaundice
Physical Examination
General condition
Hydration state
Clinical jaundice
Dermal zone
Feature of kernicterus
Dermal Zone
Bilirubin level (umol/L) 1 2 3 4 5
>250

12. Approach to Early Neonatal Jaundice
Investigations
Serum bilirubin
Blood group of mother & baby
G6PD screening result
Urine for haemstix, RBC

13. Neonatal Jaundice D3 to 1 week
Common causes
Physiological jaundice
Breast feed jaundice
G6PD deficiency
Increase red cell load
Cephalhaematoma
Polycythaemia
Blood group incompatibility

14. Physiological Jaundice
Transition from fetal to adult bilirubin metabolism
Start from D2 to D4
Reach maximum at D4 to D6
Back to normal from D5 to D7 (up to 2 week in preterm infants)
Clinically well except jaundice

15. Physiological Jaundice
Criteria that rule out physiological jaundice
Jaundice within the first 24 hours
Jaundice persist >1 week in term or >2 week in preterm infants
Velocity of rise of bilirubin > 100 umol/l/day
Bilirubin level > 250 umol/l
Conjugated bilirubin > 34 umol/l
Management : Reassurance and monitor SB

16. Breast feed jaundice Mx: Rehydration +/- phototherapy
Inadequate intake in the few few days
Wt lost > 8% of birth weight
Increase serum bilirubin
Increase serum sodium
Fever
Mx: Rehydration +/- phototherapy

17. Approach to jaundice D3 to 1 week
History
Age of onset
General well being
Type & amount of feeding
Body weight change
Urine output & color
Maternal blood group
Screening result of G6PD & Hypothyroidism

18. Approach to jaundice D3 to 1 week
Physical Examination
General condition
Body temperature
Hydration state
Clinical jaundice
Dermal zone
Feature of kernicterus

19. Approach to jaundice D3 to 1 week
Investigations
Serum bilirubin
Blood group of mother & baby
G6PD & TSH screening result
Urine for haemoglobin, RBC & WBC

20. Prolonged Neonatal Jaundice
Beyond 1 week in term infants
Beyond 2 week in preterm infants
Common & important causes
Breast milk jaundice
Obstructive jaundice
Neonatal hepatitis
Haemolysis
Metabolic - Hypothyroidism

21. Breast milk jaundice Breast milk Clinical presentation
Inhibits conjugation
Enhance hydrolysation of conjugated bilirubin
Enhance enterohepatic circulation
Clinical presentation
Prolonged jaundice beyond 1 week
Resolve in 3 to 12 weeks

22. Breast Milk Jaundice Management: Reassurance
Clinically asymptomatic except jaundice
No hepatosplenomegaly
Normal stool & urine
Normal liver function test (included conjugated bilirubin)
Other pathology e.g. haemolysis, hypothyroidism ruled out
Management: Reassurance

23. Obstructive jaundice Common causes Clinical features Biliary atresia
Choledochal cyst
Clinical features
Prolonged jaundice
Pale stool & tea color urine
Elevated direct bilirubin, g-GTP
Normal or mildly elevated liver enzymes

24. Obstructive Jaundice US Biliary tract E-Hida Scan Liver Biopsy
Diagnose choledochal cyst & other anatomical obstruction
E-Hida Scan
Radioisotope excrete via the CBD to doudenum
Liver Biopsy
Histological diagnosis of biliary atresia & hepatitis
Intra-operative Cholangiogram
Cannulation & inject contrast into CBD under direct vision

25. Neonatal hepatitis Congenital infection Acquired infection
TORCH
Acquired infection
Hepatitis viruses
Cytomegalovirus (CMV)
Epstein-Barr virus (EBV)
Neonatal hepatitis without organism identified
Autoimmune
Idiopathic

26. Neonatal Hepatitis Elevated serum bilirubin Elevated liver enzymes
both direct & indirect
Elevated liver enzymes
US – mild hepatomegaly
E-Hida: normal (may have false positive due to cholestasis)
Viral titre – Hepatisis viruses, TORCH, CMV, EBV
Urine – CMV isolation

27. Haemolysis cause prolonged jaundice
G6PD deficiency
RBC Membrane defect
Hereditary spherocytosis
Haemoglobinopathy
a-thalassaemia
Usually present with anaemia rather than jaundice

28. Hypothyroidism Common in HK (1 in 4,000)
Clinical features like coarse face, macroglossia, constipation & abdominal distention all develop after 2 ~ 3 months of age
Prolong jaundice may be the only early sign
Check Hypothyroid screening result can prevent irreversible brain damage

29. Approach to prolonged neonatal jaundice
History
Antenatal history suggested congenital infection
Onset & progress of jaundice
Type of feeding
Urine & Stool colour
Newborn cord blood screening result
Family history of jaundice

30. Approach to prolonged neonatal jaundice
Physical Examination
General well being
Rash or petechiae
Hepatosplenomegaly
Features suggest hypothyroidism
Examine stool & urine

31. Approach to prolonged neonatal jaundice
Investigation
Serum bilirubin – direct & indirect, liver enzymes, g-GTP
Urine for bile & urobilinogen
Conjugated hyperbilirubinaemia
Viral titre & urine for CMV
US biliary tract +/- E-Hida scan
Unconjugated hyperbilirubinaemia
CBC, Blood smear if unconjugated hyperbilirubinaemia

32. Jaundice beyond neonatal period
Heterogenous etiologies
Common or important causes
Pre-hepatic
Hemolysis: Hereditary spherocytosis, Thalassaemia, G6PD deficiency
Hepatic
Infective hepatitis
Drug induced hepatitis
Hepatocellular failure: cirrhosis, malignancy
Metabolic: Wilson’s disease, a-1-antitrypsin deficiency
Obstructive
Biliary stones
Cystic fibrosis

33. Approach History Onset & progress of jaundice Associated symptoms
Fever, abdominal pain
Urine colour
Stool colour
Drug history
Neonatal screening of G6PD status
Family history of jaundice

34. Physical Examination Jaundice – Sclera Pallor
Stigmata of chronic liver disease
Abdominal Examination
Hepatomegaly – tender liver
Splenomegaly
Ascite

35. Investigation Direct & Total bilirubin Liver enzymes
Viral titre for hepatitis
HAV, HBV, EBV
Urine for bile, urobilinogen
CBC, blood smear
Hb pattern, reticulocyte count if indicated
US Abdomen if indicated

36. Phototherapy
converting bilirubin to lumirubin that bypass liver conjugating system
Effectiveness depends on
light irradiance
exposed body area
wavelength of light, best 450nm i.e. blue light

37. Side effects of Phototherapy
Ý body temp & fluid lost due to radiant heat
loose stool : photodegradation products
retinal damage : eye shield
photo rash : UV light induced mast cell damage
bronze baby syndrome : phototherapy in obstructive jaundice, ? accumulation of lumirubin under skin

38. Exchange Transfusion Mechanism Type of blood used Remove bilirubin
Remove antibodies
Type of blood used
citrate phosphate dextrose (CPD) banked blood
freshly collected < 5 days
compatible with baby & mother’s blood group
Rh-ve in case of Rh incompatibility

39. Exchange Transfusion Volume of exchange transfusion Method
2 times blood volume
remove 87% of total bilirubin theoretically
45% of original level may still remain & rebound to 60% due to redistribution
Method
Umbilical vein catheterization
peripheral artery & vein

40. Push & Pull Vs Isovolumetric technique
Blood Volume
Time

41. Complication of Exchange Transfusion
umbilical catheterization: embolism, portal vein thrombosis
peripheral artery : ischaemia of extremity
haemodynamic distrubance : hypotension, arrhythmia
coagulation : thrombocytopenia
metabolic : hyperkalemia, hypocalcemia, hypoglycemia
infection : HIV, CMV, Hepatitis viruses