Jaundice – neonatal, prolonged and beyond

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 (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

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

26. Neonatal Hepatitis • Elevated serum bilirubin • 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 • 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 • 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 VsIsovolumetric 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