Effect of Free Fatty Acids on Bilirubin-Albumin Binding Affinity and Unbound Bilirubin in Premature Infants

Background: The author has previously shown that intravenous lipid intake may be associated with an increase in unbound bilirubin in infants <= 28 weeks gestational age. The objective of this study was to evaluate whether this increase in unbound bilirubin is mediated by free fatty acids and to examine the secondary effect of free fatty acids on bilirubin-albumin binding affinity. Methods: A prospective study was conducted to include 26 infants <= 32 weeks gestational age with indirect hyperbilirubinemia and receiving intravenous lipids during the first 10 postnatal days. Blood samples were collected for unbound bilirubin, binding affinity, and free fatty acid measurement at varying intravenous lipid intakes (1-3 g/kg/d). Regression analyses were performed to evaluate the roles of free fatty acids and binding affinity as mediators. Results: Intravenous lipid intake was significantly associated with an increase in free fatty acids and unbound bilirubin in infants <= 28 weeks but not > 28 weeks gestational age. In infants <= 28 weeks gestational age, each unit increase in free fatty acids was significantly associated with a decrease in binding affinity, which was significantly associated with an increase in unbound bilirubin. Conclusions: In infants <= 28 weeks gestational age, intravenous lipid intake may be associated with an increase in unbound bilirubin, and this is mediated by an increase in free fatty acids and a secondary decrease in binding affinity. In infants > 28 weeks gestational age, higher intravenous lipid intake may be used because it is unassociated with increases in free fatty acids and unbound bilirubin. (JPEN J Parenter Enteral Nutr. 2010; 34: 414-420)