Neonatal Cholestasis
Neonatal cholestasis is conjugated hyperbilirubinaemia, defined as a conjugated bilirubin over 17 micromol/L (1 mg/dL) when total bilirubin is under 85 micromol/L (5 mg/dL), or over 20% of total bilirubin when total is over 85 micromol/L. Any infant jaundiced beyond 14 days (21 days if preterm) needs fractionated bilirubin.
It affects about 1 in 2500 live births. Biliary atresia accounts for about 25 to 35% of cases, and is the most urgent cause because survival with the native liver depends on early surgery.
Causes, roughly by frequency, are:
- Biliary atresia and idiopathic neonatal hepatitis.
- Infection: cytomegalovirus, urinary tract infection and sepsis, syphilis, toxoplasmosis, hepatitis B.
- Metabolic and genetic: alpha-1 antitrypsin deficiency, galactosaemia, tyrosinaemia type 1, Alagille syndrome, progressive familial intrahepatic cholestasis, bile acid synthesis defects, cystic fibrosis, citrin deficiency and mitochondrial disease.
- Endocrine: hypothyroidism and hypopituitarism.
- Parenteral nutrition associated cholestasis and gestational alloimmune liver disease.
Pathophysiology.
Impaired bile formation or bile flow causes retention of bile acids, bilirubin and cholesterol in hepatocytes and the biliary tree. This injures hepatocytes and bile ducts and leads to fibrosis.
Reduced bile acid in the gut causes fat and fat soluble vitamin malabsorption, with coagulopathy, rickets and growth failure.
