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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.

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