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Approach to evaluation of cholestasis in neonates and young infants

Kathleen M Loomes, MD
Jessi Erlichman, MPH
Section Editors
Steven A Abrams, MD
Elizabeth B Rand, MD
Deputy Editor
Alison G Hoppin, MD


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 – 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 [3]. (See "Clinical aspects of serum bilirubin determination", section on 'Measurement of serum bilirubin'.)

If direct bilirubin is measured, it is considered elevated if it is 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). If conjugated bilirubin is measured, the upper limit of normal is about 0.5 mg/dL (8.6 micromol/L). An elevation above these levels is an abnormal finding and requires additional evaluation [4].

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Literature review current through: Dec 2017. | This topic last updated: Oct 17, 2017.
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