Hyperbilirubinemia/Jaundice — Differential Diagnosis — Clinical Pathway: All Settings

Neonates with Hyperbilirubinemia/Jaundice Clinical Pathway

Differential Diagnosis for Neonatal Jaundice

Unconjugated Hyperbilirubinemia
  • Physiologic Jaundice:
    • Alteration in neonatal bilirubin metabolism:
      • Increased RBC load, increased enterohepatic circulation
      • Immature uridine diphosphate glucuronosyltransferase
  • Suboptimal Intake Hyperbilirubinemia:
    • Formerly known as Breastfeeding jaundice attributed to suboptimal intake
    • Peak at 3-5 days
  • Breast Milk Jaundice Syndrome:
    • Prolonged elevated unconjugated hyperbilirubinemia
    • Persists with adequate milk intake that can last up to 3 months
    • Usually benign
  • Increased Bilirubin Production Due to Increased Red Blood Cell Breakdown:
    • Isoimmune mediated hemolysis (e.g., ABO or RH incompatibility)
    • Red blood cell membrane defects (e.g., Hereditary Spherocytosis)
    • Red blood cell enzymatic defects (e.g., G6PD, pyruvate kinase deficiency)
    • Polycythemia
    • Extravasation of blood (e.g., cephalohematoma)
  • Decreased Bilirubin Clearance:
    • Crigler-Najjar syndrome
    • Gilbert syndrome
  • Miscellaneous Causes:
    • Infant of diabetic mother
    • Hypothyroidism
    • Intestinal obstruction
    • Sepsis
    • Medications
Conjugated Hyperbilirubinemia

Conjugated
> 1.0 mg/dL

Prompt GI, Surgery Consultation
  • Anatomic with Obstruction of Flow:
    • Biliary atresia
    • Sclerosing cholangitis
    • Choledochal cyst
    • Cholelithiasis
  • Genetic:
    • Cystic fibrosis
    • Alpha-1 antitrypsin deficiency
    • Alagille syndrome
    • Galactosemia
    • Fructosemia
  • Infections:
    • CMV, HSV, HIV, rubella, syphilis, toxoplasmosis (TORCH)
    • Urinary tract infection
    • Sepsis
    • Hepatitis B
    • Neonatal hepatitis