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

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

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

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

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

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

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

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

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

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

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 70 - 130 2 90 - 200 3 130 - 280 4 190 - 300 5 >250

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Push & Pull Vs Isovolumetric technique Blood Volume Time

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