General Overview

  • Usually due to hyperbilirubinemia (Bili >2xULN)
    • If jaundiced but normal bilirubin, consider carotenemia
  • Mostly unconjugated

DDx Unconjugated Bilirubin

  • Overproduction (hemolysis)
  • Impaired hepatic uptake (reduced blood flow, drugs)
  • Impaired conjugated (Gilber or Crigler-Najjar)

Risk for Severe Hyperbilirubinemia

  • Jaundice in first 24h of life (always pathologic)
  • Positive direct antiglobulin test (DAT/Coombs)
  • Known hemolytic disease (G6PD)
  • Premature
  • Previous sibling with severe hyperbilirubinemia/phototherapy
  • Bleeding/bruising (cephalohematoma)
  • East Asian
  • Exclusive breastfeeding


  • Prenatal, antenatal, postnatal/neonatal course
  • Family History

Physical Exam

  • Vitals r/o sepsis, r/o anemia
  • Weight, and % weight loss from BW
  • Hydration/feeding status
  • Sclerae most sensitive (if sclerae unaffected, consider carotenemia)
  • Signs of bleeding, bruising, hematoma (hemolysis)
  • Abdominal exam (hepatosplenomegaly)


  • Rule out sepsis
  • Phototherapy as indicated
  • Investigations
    • CBC (hemoglobin)
      • If no anemia, rule out liver disease
    • Total bilirubin
      • If conjugated, requires different work-up
      • Serum bilirubin q4h until decreasing then q12h until normal
    • Neonatal blood type
    • Coombs test (r/o autoimmune hemolysis)
    • Smear
    • Consider G6PD in severe hyperbilirubinemia or high risk population/family history

Hyperbilirubinemia in Infants

  • Mothers screened for ABO, Rh(D), RBC Ab
    • If mother not tested, consider blood group and DAT (Coombs test)
  • Follow-up weight (and compare to birth weight), intake, voiding, stooling, jaundice
  • TcB (Transcutaneous) screen at 72h of life and prior to discharge
    • Add TcB to 95% confidence interval to estimate maximum probably TSB concentration
    • Total serum bilirubin if abnormal TcB or clinical jaundice