Neonatal Jaundice

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Neonatal Jaundice : 

Neonatal Jaundice Dr. Samarnath Sen Staff Grade Paediatrician Doncaster Royal Infirmary

A case of neonatal jaundice I : 

2/12/2010 Neonatal Jaundice/Dr.Samarnath Sen 2 A case of neonatal jaundice I Born 37/40, well, no jaundice First child of non-consanguineous parents Discharged day 1, breast fed Re-admitted to local DGH on day 5 - total bilirubin 361 mmol/L Fractionated bilirubin: ‘ Direct ’ 73 mmol/L Given Phototherapy

A case of neonatal jaundice II : 

2/12/2010 Neonatal Jaundice/Dr.Samarnath Sen 3 A case of neonatal jaundice II 8/7 - total 251 mmol/L, ‘direct’ 70 mmol/L Stools “touch” pigmented, pale urine For OP review 5/52 - total 124 mmol/L, ‘direct’ 70 mmol/L Thyroid function - normal 6.5/52 - total 124 mmol/L, ‘direct’ 81 mmol/L Observations: mild jaundice, soft liver edge, alert and active, fixing and following

A case of neonatal jaundice III : 

2/12/2010 Neonatal Jaundice/Dr.Samarnath Sen 4 A case of neonatal jaundice III Categories to consider: Physiological versus pathological jaundice Unconjugated versus conjugated hyperbilirubinaemia Early versus prolonged jaundice Determine differential diagnosis and select further investigations

A case of neonatal jaundice IV : 

2/12/2010 Neonatal Jaundice/Dr.Samarnath Sen 5 A case of neonatal jaundice IV Prolonged conjugated hyperbilirubinaemia Differential diagnosis: infection inherited metabolic disorder biliary tree abnormality Referred to BCH for assessment of prolonged jaundice

A case of neonatal jaundice V : 

2/12/2010 Neonatal Jaundice/Dr.Samarnath Sen 6 A case of neonatal jaundice V

A case of neonatal jaundice VI : 

2/12/2010 Neonatal Jaundice/Dr.Samarnath Sen 7 A case of neonatal jaundice VI

A case of neonatal jaundice VII : 

2/12/2010 Neonatal Jaundice/Dr.Samarnath Sen 8 A case of neonatal jaundice VII Final diagnosis Extra-hepatic biliary atresia Management Surgery - Kasai hepatoportoenterostomy Drug therapy - low dose oral antibiotics - bile acid supplement Nutritional support - fat soluble vitamins

A case of neonatal jaundice VIII : 

2/12/2010 Neonatal Jaundice/Dr.Samarnath Sen 9 A case of neonatal jaundice VIII Follow up two admissions - jaundice and evidence of increasingly severe hepatocellular and canalicular cholestasis. Found to have proliferating bile ductules and thickened bile. results consistent with biliary cirrhosis secondary to EHBA and consistent with a failed Kasai operation. Liver transplant at 7.5 months of age.

Physiological vs Pathological Neonatal Jaundice : 

2/12/2010 Neonatal Jaundice/Dr.Samarnath Sen 10 Physiological vs Pathological Neonatal Jaundice Physiological jaundice Up to 50% of normal babies Occurs 2 - 10 days (peak 3 - 4 days) Total bilirubin < 200 mmol/L (pre-term higher) Conjugated bilirubin < 20 mmol/L Normal by 7 - 10 days Baby well and thriving May be associated with bruising/birth trauma, prematurity, breast feeding, and/or dehydration

Physiological vs Pathological Neonatal Jaundice : 

2/12/2010 Neonatal Jaundice/Dr.Samarnath Sen 11 Physiological vs Pathological Neonatal Jaundice Pathological jaundice Early jaundice - within first 24 hours Jaundice in a sick neonate Total bilirubin high - >300 mmol/L Rapid increase - >100 mmol/L in 24 hours Prolonged - present after 14 days Conjugated - > 20 mmol/L Associated pathologies - isoimmunisation, infection, hypothyroidism, biliary atresia, metabolic disorders

Early jaundice I : 

2/12/2010 Neonatal Jaundice/Dr.Samarnath Sen 12 Early jaundice I Haemolytic disorders Excessive breakdown of RBC Presents as early unconjugated jaundice or, if severe, anaemia Blood group incompatibility Intrinstic red cell abnormalities Spherocytosis Glucose-6-phosphate dehydrogenase deficiency Pyruvate kinase deficiency Bruising/Haemorrhage

Early jaundice II : 

2/12/2010 Neonatal Jaundice/Dr.Samarnath Sen 13 Early jaundice II Infection (intrauterine & perinatal) Infections Unconjugated/conjugated hyperbilirubinaemia in sick infant Hepatitis with bilirubinuria, pale stools and liver enzymes Inherited disorders of bilirubin metabolism Generally very rare inherited defects - Gilberts, CNI, CNII Should only be considered after exclusion of commoner causes unless family history

Inherited disorders of bilirubin metabolism : 

2/12/2010 Neonatal Jaundice/Dr.Samarnath Sen 14 Inherited disorders of bilirubin metabolism

Investigation of early jaundice : 

2/12/2010 Neonatal Jaundice/Dr.Samarnath Sen 15 Investigation of early jaundice Total and fractionated bilirubin concentrations Haematology Hb Blood group FBC including reticulocytes Coombs Test Film Glucose - 6 - phosphate dehydrogenase screen ? Other red cell enzymes Infection screen - TORCH, urine culture

Prolonged Jaundice : 

2/12/2010 Neonatal Jaundice/Dr.Samarnath Sen 16 Prolonged Jaundice Prematurity (U) Breast feeding (U) Congenital infections/immune disorders (U/C) Parenteral nutrition (C) Endocrine disorders (U/C) Genetic disorders (U/C) Bilirubin transport defects (C)

Signs of liver dysfunction : 

2/12/2010 Neonatal Jaundice/Dr.Samarnath Sen 17 Signs of liver dysfunction Conjugated bilirubin >20 mmol/L Pale stools Bilirubin in urine Bleeding/ prolonged clotting FTT Hypoglycaemia Abnormal LFTs

Endocrine disorders presenting with jaundice : 

2/12/2010 Neonatal Jaundice/Dr.Samarnath Sen 18 Endocrine disorders presenting with jaundice Hypothyroidism Infrequently  unconjugated hyperbilirubinaemia ?Neonatal screening TSH/FT4 Hypopituitarism Infrequently  usually conjugated hyperbilirubinaemia ? Hypoglycaemia Cortisol

Genetic disorders presenting with jaundice : 

2/12/2010 Neonatal Jaundice/Dr.Samarnath Sen 19 Genetic disorders presenting with jaundice Red cell enzyme defects (G6PD & PK deficiency) (U) Bilirubin metabolism defects (U) Alpha-1-antitrypsin deficiency (C) Galactosaemia/fructosaemia (C) Tyrosinaemia type I (C) Cystic fibrosis (C) Bilirubin transport defects (C) Lysosomal storage disorders (C) Peroxisomal disorders (Zellwegers) (C)

Bilirubin transport defects : 

2/12/2010 Neonatal Jaundice/Dr.Samarnath Sen 20 Bilirubin transport defects Biliary atresia Extra-hepatic loss of biliary tree Alagille’s Syndrome Intrahepatic biliary hypoplasia Bile salt transport defects Congenital cholestasis with conjugated hyperbilirubinaemia

Investigation of prolonged jaundice I : 

2/12/2010 Neonatal Jaundice/Dr.Samarnath Sen 21 Investigation of prolonged jaundice I Total and fractionated bilirubin concentrations LFTs, haematology, infection screen Thyroid function tests - ? neonatal screening test G6PD - ? at risk/ screening Alpha-1-antitrypsin concentration & phenotype Sweat test / IRT Plasma cortisol Urine sugars / red cell galactose-1-phosphate uridyl transferase Amino acids (urine & plasma) Organic acids (urine) Acylcarnitines

Investigation of prolonged jaundice II : 

2/12/2010 Neonatal Jaundice/Dr.Samarnath Sen 22 Investigation of prolonged jaundice II Ultra sound Isotope scan Liver biopsy Bile acids VLCFA - peroxisomal function Lysosomal enzymes DNA for bile salt transporter defects

Extra-hepatic biliary atresia I : 

2/12/2010 Neonatal Jaundice/Dr.Samarnath Sen 23 Extra-hepatic biliary atresia I Epidemiology Incidence in UK ~ 1 in 10,000 - 1 in 15,000 live births Significant cause of neonatal liver disease & the main indication for Tx Aetiology unclear Rarely family history Presentation Present at birth Conjugated hyperbilirubinaemia shortly after birth Pale stools and increased urinary bilirubin Hepatomegaly - early feature Slow weight gain

Extra-hepatic biliary atresia II : 

2/12/2010 Neonatal Jaundice/Dr.Samarnath Sen 24 Extra-hepatic biliary atresia II Pathology Extra-hepatic loss of biliary tree Biochemistry Conjugated bilirubin:total bilirubin >20% Elevated aminotranferases (cf neonatal hepatitis) Elevated ALP and g GT Diagnosis visualisation of gall bladder and biliary tree on US radio-isotope excretion scan (T-BIDA scan) liver histology cholangiogram

Extra-hepatic biliary atresia III : 

2/12/2010 Neonatal Jaundice/Dr.Samarnath Sen 25 Extra-hepatic biliary atresia III Management Surgery - Kasai hepatoportoenterostomy Drug therapy - low dose oral antibiotics Nutritional support - calories & fat soluble vitamins Family support

Extra Hepatic Biliary atresia : 

2/12/2010 Neonatal Jaundice/Dr.Samarnath Sen 26 Extra Hepatic Biliary atresia Prognosis Complications inc. recurrent ascending cholangitis, progressive biliary cirrhosis and portal hypertension. Malnutrition secondary to malabsorption Progression to cirrhosis and portal hypertension inevitable If surgery unsuccessful - liver Tx within 1 year Liver transplant Require specialist follow up

Take home message : 

2/12/2010 Neonatal Jaundice/Dr.Samarnath Sen 27 Take home message Investigate a neonate with prolonged jaundice promptly. Measure bilirubin fractions to determine the nature of the hyperbilirubinaemia. Exclude, where possible, other causes of conjugated hyperbilirubinaemia. Be aware that the Kasai operation for biliary atresia is less likely to be successful after the infant is 8 weeks old.