Your next patient is a 17 day old presenting for follow-up. During the visit you note that the baby’s eyes and skin are yellow.  Labs show a total bilirubin of 7 mg/dL, with direct component being 5mg/dl. What are your next steps?

What is Jaundice?

  • A yellowish discoloration of the skin and sclera due to elevated bilirubin levels in the blood.
    • Associated findings include: pale stool, dark urine
    • Becomes clinically apparent at total levels >2.5mg/dL (Fawaz  et al, 2016)
  • Very common finding; found in up 15% of infants at 2 week visit (Kelly et al, 1995)

What is Bilirubin?

  • Breakdown product of heme metabolism
  • Conjugated in the Liver
  • Excreted in feces (majority) and urine

Approach to A Jaundiced Neonate (adapted from NASPGHAN guidelines; Moyer et al, 2004)

Step 1: Is the baby sick?
  • Differential includes: infection (especially urinary tract), inborn errors of metabolism, acute hemolysis, etc
  • Most important: manage acute illness
Step 2:  What type of hyperbilirubinemia?
  1. Direct
    • Defined as a serum conjugated bilirubin >1.0mg/dl if serum total bilirubin is <5.0 mg/dl or >20% of total bilirubin if >5 mg/dL. (Shulman et al, 2016)

Figure 1: Most Common Etiologies of Neonatal Cholestasis

Etiology Number of Cases (Total: 1692) % of Cases
Idiopathic Neonatal Hepatitis 440 26
Extrahepatic Biliary Atresia 438 25.9
Infection 194 11.5
Metabolic Disease 74 4.4

Adapted from Gottesman et al, 2015

    2.) Indirect Hyperbilirubinemia

  • Most commonly due breast milk jaundice, though larger differential exists. Will not be discussed during this post.
Step 3: Other Labs and Studies
  1. Important Imaging Studies
    • Ultrasound- wide estimates of sensitivity
      • 73-100% for absent gallbladder and 83-100% for “triangular cord” sign depending on study cited.
  2. Other labs/blood to obtain
    • Review Newborn Screen: Congenital hypothyroidism and galactosemia can present with cholestasis.
    • GGTP, LFTs, CBC, Coags
    • α-1 antitrypsin (If low, order Pi Typing)
 Next Steps
  • Next steps largely depend on findings of workup listed above
  • As biliary atresia (BA) can cause neonatal cholestasis, this MUST be ruled out
    • Outcome of patients diagnosed with biliary atresia is inversely correlated with age of diagnosis (specifically the age at which they undergo the Kasai hepatoportoenterostomy (Balistreri et al, 1996)
    • If ultrasound non-diagnostic, hepatobiliary scintigrapy (HDS), magnetic resonance cholangiopancreatography (MRCP), liver biopsy may need to be undertaken to rule out BA
      • Note: Gold standard is intra-op cholangiogram (Shulman et al, 2016)
Faculty Reviewer: Jason Shapiro, MD
Resident Reviewer: Meg Gibson, MD


  • Balistreri WF et al. “Biliary Atresia: Current Concepts and Research Directions.” Hepatology. 1996;23(6)1682-1692.
  • Fawaz R et al. “Guideline for the Evaluation of Cholestatic Jaundice in Infants: Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition.” Journal of Pediatric Gastroenterology and Nutrition. 2016; (Published ahead of print)
  • Gottesman LE, Del Vecchio MT, Aronoff SC. “Etiologies of conjugated hyperbilirubinemia in infancy: A systematic review of 1692 subjects.” BMC Pediatrics 2015; 15:192
  • Kelly DA et al. “Jaundice in Babies: Implications for Community Screening for Biliary Atresia.” The British Medical Journal. 1995;310(6988)1172-1173.
  • Moyer M et al. “Guideline for the Evaluation of Cholestatic Jaundice in Infants: Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition.”Journal of Pediatric Gastroenterology and Nutrition. 2004;39(2)115-128
  • Shulman RJ et al. “Approach to Neonatal Cholestasis.” Accessed July 5th, 2016.