Guideline for the Evaluation of Cholestatic Jaundice in Infants: Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition

For the primary care provider, cholestatic jaundice in infancy, defined as jaundice caused by an elevated conjugated bilirubin, is an uncommon but potentially serious problem that indicates hepatobiliary dysfunction. Early detection of cholestatic jaundice by the primary care physician and timely, accurate diagnosis by the pediatric gastroenterologist are important for successful treatment and a favorable prognosis. The Cholestasis Guideline Committee of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition has formulated a clinical practice guideline for the diagnostic evaluation of cholestatic jaundice in the infant. The Cholestasis Guideline Committee, consisting of a primary care pediatrician, a clinical epidemiologist (who also practices primary care pediatrics), and five pediatric gastroenterologists, based its recommendations on a comprehensive and systematic review of the medical literature integrated with expert opinion. Consensus was achieved through the Nominal Group Technique, a structured quantitative method. The Committee examined the value of diagnostic tests commonly used for the evaluation of cholestatic jaundice and how those interventions can be applied to clinical situations in the infant. The guideline provides recommendations for management by the primary care provider, indications for consultation by a pediatric gastroenterologist, and recommendations for management by the pediatric gastroenterologist. The Cholestasis Guideline Committee recommends that any infant noted to be jaundiced at 2 weeks of age be evaluated for cholestasis with measurement of total and direct serum bilirubin. However, breast-fed infants who can be reliably monitored and who have an otherwise normal history (no dark urine or light stools) and physical examination may be asked to return at 3 weeks of age and, if jaundice persists, have measurement of total and direct serum bilirubin at that time. This document represents the official recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition on the evaluation of cholestatic jaundice in infants. The American Academy of Pediatrics has also endorsed these recommendations. These recommendations are a general guideline and are not intended as a substitute for clinical judgment or as a protocol for the care of all patients with this problem. BACKGROUND Cholestatic jaundice, characterized by elevation of serum conjugated bilirubin, is an uncommon but potentially serious condition that indicates hepatobiliary dysfunction. Early detection of cholestatic jaundice by the primary care provider and timely, accurate diagnosis by the pediatric gastroenterologist are important for successful treatment and a favorable prognosis. In contrast, physiologic jaundice and breast milk jaundice, common causes of jaundice in the first weeks of life, are caused by an elevation of serum unconjugated bilirubin. Both are self-limited maturational disorders observed in many infants in the first weeks of life. Cholestatic jaundice affects approximately 1 in every 2,500 infants (1,2), and is thus infrequently seen by most providers of medical care to infants. However, distinguishing jaundice caused by cholestasis from noncholestatic conditions is critical because cholestatic jaundice is much more likely to have a serious etiology that needs prompt diagnosis and therapy. The most common causes of cholestatic jaundice in the first months of life are biliary atresia and neonatal hepatitis, which account for most cases. Neonatal hepatitis has referred to a histologic appearance of widespread giant cell transformation. Although giant cell transformation is recognized to be nonspecific and may be associated with infectious, metabolic, and syndromic disorders, this term is used to be consistent with the older literature reviewed for this guideline. Alpha-1 antitrypsin deficiency causes another 5% to 15% of cases (1,2). The remaining cases are caused by a variety of other disorders, including extrahepatic obstruction from common duct gallstone or choledochal cyst; metabolic disorders such as tyrosinemia, galactosemia, and hypothyroidism; inborn errors of bile acid metabolism; Alagille syndrome; infection; and other rare disorders (Table 1). Infants with cholestatic jaundice caused by bacterial sepsis, galactosemia, hypopituitarism, or gallstone often appear acutely ill. These disorders require early diagnosis and urgent treatment. However, many infants with cholestatic jaundice appear otherwise healthy and grow normally. The benign appearance of such an infant may lull the parents or physician into believing that the jaundice is physiologic or caused by breast-feeding, when in fact it may be caused by biliary atresia. Biliary atresia occurs in 1 in 10,000 to 19,000 infants (3–6) (Elliott EJ, Australian Pediatric Surveillance Unit, Extra-hepatic Biliary Atresia Study Group, personal communication, Journal of Pediatric Gastroenterology and Nutrition 39:115–128 © August 2004 Lippincott Williams & Wilkins, Philadelphia