Case:

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

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

References

• 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.” http://www.uptodate.com/contents/approach-to-neonatal-cholestasis. Accessed July 5th, 2016.