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I. PROBLEM

An infant’s direct (conjugated) serum bilirubin level is elevated at 3 mg/dL. Conjugated bilirubin is the fraction of bilirubin that is conjugated with glucuronic acid in the liver to form bilirubin diglucuronide. It is a biochemical marker of cholestasis. Neonatal cholestasis is conjugated hyperbilirubinemia in the newborn period and is an accumulation of bile substances in the liver. It is secondary to decreased bile secretion from the liver to the duodenum and usually signifies an underlying hepatobiliary or metabolic dysfunction. Cholestasis can be extrahepatic/obstructive (most commonly biliary atresia, other causes include choledochal/biliary cyst, inspissated bile syndrome, obstructive tumors, gallstones) or intrahepatic/nonobstructive (idiopathic, infectious, metabolic/genetic, autoimmune, or toxic). This chapter incorporates recommendations from the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN), the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN), and the American Academy of Pediatrics (AAP) on the management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. NASPGHAN defines an abnormal direct bilirubin as >1 mg/dL. The AAP defines an abnormal direct bilirubin as >1 mg/dL if the total serum bilirubin (TSB) level is ≤5 mg/dL. If the TSB level is >5 mg/dL, a direct bilirubin >20% of the TSB is abnormal. The majority of prolonged physiologic jaundice is secondary to breast milk jaundice, but it is important not to misdiagnose cholestasis as physiologic jaundice because this will delay the early diagnosis that is essential for treatment. Conjugated hyperbilirubinemia is never normal or physiologic and indicates hepatobiliary dysfunction. It occurs in 1 in every 2500 term infants, and common causes in the newborn infant are biliary atresia (25%–40%), monogenic disorders (25%), and multifactorial or unknown etiologies. The more common causes in premature infants are prolonged parenteral nutrition and sepsis. Timely diagnosis is critical for successful treatment and optimal prognosis, in particular for biliary atresia. Kasai hepatic portoenterostomy should be done as soon as possible to establish bile flow and is best performed within the first 60 days of life (approximately 70% with bile flow vs <25% with bile flow at >90 days). See also Chapter 98 for additional discussion on conjugated hyperbilirubinemia management.

II. IMMEDIATE QUESTIONS

  1. What is the stool and urine color?

    1. Dark urine. The presence of dark urine is a nonspecific indicator of increased conjugated bilirubin.

    2. Stool color. A stool examination is vital to the workup of every infant with cholestasis. A persistent pale or clay-colored stool suggests an extrahepatic obstruction/biliary obstruction. When bile flow decreases, the stool starts to lose its normal pigmentation. One or 2 pale stools usually do not indicate disease, and infants with biliary atresia can have normal stools.

      1. Pale/clay/depigmented stool with increased serum bilirubin can be associated with biliary atresia, choledochal/biliary cyst, biliary sludge (inspissated bile syndrome), Alagille syndrome, neonatal sclerosing cholangitis, cystic fibrosis, and α1-antitrypsin deficiency.

      2. Normal stool with increased serum bilirubin: Consider infection, hypothyroidism, panhypopituitarism, cystic fibrosis, α1-antitrypsin, progressive familial intrahepatic cholestasis ...

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