Parenteral Nutrition–Associated Conjugated Hyperbilirubinemia in Hospitalized Infants

Abstract

Parenteral nutrition-associated conjugated hyperbilirubinemia (PNAC), commonly defined as direct bilirubin ≥2 mg/dL (34.2 μmol/L), is primarily a pediatric disease with premature infants being the most susceptible. Severe morbidity and increased mortality are associated with bilirubin >10 mg/dL (171.0 μmol/L). The lack of knowledge regarding the cause of PNAC has stymied development of prevention and treatment strategies. A systematic search of published reports was conducted to provide data on histopathology of PNAC and to review prospective, randomized, controlled trials in hospitalized infants. In experiments of young animals, parenteral nutrition (PN) with and without soy oil emulsion is directly linked to hyperbilirubinemia, and the effects are exaggerated by overfeeding. In infants, the most consistently reported risk factor for PNAC is the duration of PN. The only known effective modality is the transition to full enteral feeding and discontinuation of PN. Emerging clinical research is evaluating the role of lipid source (soy vs fish) and motility agents, such as erythromycin. Different trace element preparations are associated with varying severity of cholestasis, a finding that also deserves more study. This article reviews the prevalence, risk factors, clinical presentation, and treatment options for PNAC in neonatal intensive care units.