Neonatal cholestasis is generally defined as prolonged conjugated hyperbilirubinemia that occurs in the newborn period. It results from diminished bile flow 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 parenteral nutrition-associated cholestasis), 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 neonatal cholestasis".)
Cholestasis is defined as an impairment in the excretion of bile, which can be caused by defects in intrahepatic production or 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 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 parenteral nutrition-associated liver disease. (See "Parenteral nutrition-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 overestimates conjugated bilirubin, particularly when the concentrations of total serum bilirubin are high . (See "Clinical aspects of serum bilirubin determination", section on 'Measurement of serum bilirubin'.)