Etiologies of conjugated hyperbilirubinemia in infancy: a systematic review of 1692 subjects

Background: The etiologies of conjugated hyperbilirubinemia in infancy are diverse. Objective: Determine the prevalence rates of the specific etiologies of conjugated hyperbilirubinemia in infancy. Data sources: EMBASE and Pubmed were searched electronically and the bibliographies of selected studies were search manually. The search was conducted independently by two authors. Study selection: (1) prospective or retrospective case series or cohort study with 10 or more subjects; (2) consecutive infants who presented with conjugated hyperbilirubinemia; (3) subjects underwent appropriate diagnostic work-up for conjugated hyperbilirubinemia; (4) no specific diagnoses were excluded in the studied cohort. Data extraction: Patient number, age range, country of origin, and categorical and specific etiologies. Results: From 237 studies identified, 17 studies encompassing 1692 infants were selected. Idiopathic neonatal hepatitis (INH) occurred in 26.0 % of cases; the most common specific etiologies were extrahepatic biliary atresia (EHBA) (25.89 %), infection (11.47 %), TPN-associated cholestasis (6.44 %), metabolic disease (4.37 %), alpha-1 anti-trypsin deficiency (4.14 %), and perinatal hypoxia/ischemia (3.66 %). CMV was the most common infection identified (31.51 %) and galactosemia (36.49 %) was the most common metabolic disease identified. Limitations: Major limitations are: (1) inconsistencies in the diagnostic evaluations among the different studies and (2) variations among the sample populations. Conclusions: INH is the most common diagnosis for conjugated hyperbilirubinemia in infancy while EHBA and infection are the most commonly identified etiologies. The present review is intended to be a guide to the differential diagnosis and evaluation of the infant presenting with conjugated hyperbilirubinemia.