Approach to evaluation of cholestasis in neonates and young infants
- Kathleen M Loomes, MD
Kathleen M Loomes, MD
- Associate Professor of Pediatrics
- Perelman School of Medicine at the University of Pennsylvania
- Jessi Erlichman, MPH
Jessi Erlichman, MPH
- Research Coordinator
- Children's Hospital of Philadelphia
- Section Editors
- Steven A Abrams, MD
Steven A Abrams, MD
- Section Editor — Neonatology
- Professor, Department of Pediatrics
- Dell Medical School at the University of Texas at Austin
- Elizabeth B Rand, MD
Elizabeth B Rand, MD
- Section Editor — Pediatric Hepatology
- Professor of Pediatrics
- University of Pennsylvania School of Medicine
Neonatal cholestasis is generally defined as conjugated hyperbilirubinemia that occurs in the newborn period or shortly thereafter. Cholestasis results from diminished bile formation and/or excretion, which can be caused by a number of disorders. Neonatal cholestasis lasting more than two weeks affects approximately 1 in 2500 births (excluding infants with intestinal failure-associated liver disease), but estimates vary depending on the definition used to define cholestasis [1,2].
This topic review provides an approach to patients with neonatal cholestasis. The pathogenesis and management of neonatal unconjugated hyperbilirubinemia and common causes of neonatal cholestasis are discussed separately. (See "Pathogenesis and etiology of unconjugated hyperbilirubinemia in the newborn" and "Treatment of unconjugated hyperbilirubinemia in term and late preterm infants" and "Causes of cholestasis in neonates and young infants".)
●Cholestasis – Cholestasis is defined as an impairment in the excretion of bile, which can be caused by defects in intrahepatic production of bile, transmembrane transport of bile, or mechanical obstruction to bile flow. The biochemical features of cholestasis reflect the retention of components of bile in the serum (eg, bilirubin, bile acids, and/or cholesterol). The pattern and severity of each of these abnormalities varies with the underlying disorder. Elevated conjugated bilirubin is the predominant characteristic in most of the causes of neonatal cholestasis.
●Conjugated hyperbilirubinemia – Conjugated hyperbilirubinemia in a neonate is defined as a serum conjugated bilirubin concentration greater than 1.0 mg/dL (17.1 micromol/L) if the total serum bilirubin is <5.0 mg/dL (85.5 micromol/L) or greater than 20 percent of the total serum bilirubin if the total serum bilirubin is >5.0 mg/dL (85.5 micromol/L). An elevated conjugated bilirubin is an abnormal finding and requires additional evaluation . The threshold is somewhat higher, usually a serum conjugated bilirubin greater than 2.0 mg/dL (34.2 micromol/L), for defining clinically significant hyperbilirubinemia in infants with intestinal failure-associated liver disease (which is also known as parenteral nutrition-associated liver disease). (See "Intestinal failure-associated liver disease in infants", section on 'Definition'.)
The terms "conjugated bilirubin" and "direct bilirubin" are often used interchangeably because conjugated bilirubin can be estimated by the "direct" reaction with a diazo reagent (van den Bergh reaction). However, direct-reacting bilirubin includes both the conjugated bilirubin and the delta fraction, which represents bilirubin covalently bound to albumin . (See "Clinical aspects of serum bilirubin determination", section on 'Measurement of serum bilirubin'.)
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- Initial screening
- Stages of evaluation
- PHYSICAL EXAMINATION
- LABORATORY STUDIES
- Initial tests
- Other laboratory tests
- IMAGING STUDIES
- ADDITIONAL TESTS
- Liver biopsy
- - Open cholangiogram
- - ERCP
- SUMMARY AND RECOMMENDATIONS