Definition (Pediatr Rev 2011;32:341; Pediatr Rev 2007;28:83)
• Neonatal Hyperbili (>35 wk): TSB >95th %ile for hrs of age on Bhutani nomogram
• Visible on exam at TSB 4–5 mg/dL, progressing from head down
• Older children/adults: Generally TSB >2–3 mg/dL with yellow sclera +/− skin
• Direct hyperbilirubinemia: >2 mg/dL or >20% of TSB; marker of cholestasis
Pathogenesis
• Heme catabolism in liver and spleen results in unconj bili bound to albumin in blood
• Circulating bili travels to hepatocytes → conjugated (UGT) and excreted in bile via biliary sys to small intestine → majority excreted, some (more in neonates) deconjugated by gut bacteria and reabsorbed/recycled (enterohepatic circulation)
Differential and Evaluation
• Neonatal unconjugated (indirect) bilirubin excess can be a result of:
• Increased production: Isoimmune-mediated hemolysis, hereditary RBC abn (hereditary spherocytosis [HS]/elliptocytosis [HE]), G6PDD, PKD, polycythemia, resorbing cephalohematoma, sepsis/UTI
• Decreased clearance: Normally dec in neonate, Crigler–Najjar I and II, Gilbert
• Increased enterohepatic circulation: Breast-feeding, breast milk, SBO
• Evaluation: Based on response to light therapy and adequate fluid intake
• H&P, CBC w/ diff, retic count, periph blood smear, type, Coombs, f/u NBS
• Consider UA/Ucx, blood cx given presentation, risk factors
• Neonatal conjugated (direct) hyperbilirubinemia (Pediatr Rev 2004;25:388)
• Obstruction: Biliary atresia (30%), Alagille syndrome, choledochal cyst
• Infection: Sepsis, TORCH (5%; Toxo, syphilis, HBV, CMV, HSV, rubella) parvo
• Metabolic/genetic (30%): Alpha-1-antitrypsin def (10%), galactosemia, tyrosinemia, Rotor, Dubin–Johnson, CF
• Misc: Idiopathic neonatal hepatitis, hypopituitarism, hypothyroidism
• Turner, Trisomy 18, Trisomy 21
• Toxin mediated, TPN cholestasis
• Evaluation: Focused w/u based on maternal screening/risks, H&P, need to r/o emergencies, sepsis, biliary atresia, galactosemia
• LFTs w/ GGT, albumin, PT, ammonia, CMP, CBC, TSH/T4 (newborn screen), alpha-1-AT, urine reducing substances (galactosemia)
• RPR, HSV serology, blood and urine cx, UA, serum bile acids, iron studies, transferrin, serum AA, urine OA (tyrosinemia), sweat chloride
• Stool color cards effective screen for biliary atresia (Pediatrics 2011;128:e1209)
• Abdominal U/S, HIDA scan (pretreat with phenobarbital)
• Liver biopsy
• Children/adolescent with unconjugated bilirubin excess (Pediatr Rev 2001;22:219)
• Overproduction: Hemolysis (PKD, G6PDD, HS, HE, autoimmune hemolysis), sickle cell or thalassemia, resorption of hematoma
• Impaired conjugation: Gilbert (AR), Crigler–Najjar (AR)
• Eval: H&P, CBC diff, bilis, periph smear, Coombs, haptoglobin and retic count, G6PD level, Hgb electropheresis
• Children/adolesc w/ conjugated (direct) bilirubin excess (Pediatr Rev 2001;22:219)
• Extrahepatic cholestasis: Biliary tract disorders (cholelithiasis, cholecystitis, TPN)
• Intrahepatic cholestasis: Rotor, Dubin–Johnson
• Hepatocellular injury: See Hepatitis, viral, metabolic, autoimmune, drugs, toxin
• Eval: Focused by H&P, risk factors; LFTs, synthetic labs (PT, albumin), abd U/S +/− Doppler (? Budd–Chiari), hep serologies, alpha-1-antitrypsin level, ceruloplasmin, 24-hr urine copper, ANA, ASMA, antiLKM Ab, liver bx
• Red flags: Encephalopathy, ↑ing Cr, vit K resistant ↑ PT, bili >18 mg/dL, hypoglycemia