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

Abstract

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.

Fluorescence Sensor for the Quantification of Unbound Bilirubin Concentrations

“…Neonatal HSA concentrations depend on gestational age, ranging from 280 to 470 mol/L (30 ). In neonates receiving Intralipid, FFA concentrations increase severalfold, resulting in substantial displacement of bilirubin from HSA and, therefore, large increases in B f concentrations (23,26,27 ). This variability in bilirubin-binding capacity can result in patients having similar plasma B T but different B f .…”

“…The adult-neonate difference in rate constants is still unexplained but might be related to FFA-albumin interactions (33 ). Neonates have higher plasma FFA concentrations than adults, and this may promote bilirubin dissociation leading to increased B f (19,22,23,27 ). Infusion of intralipid may reduce the 375-nm excitation intensity through increased light scattering and might yield erroneously high B f values by BL22P1B11 but not BL22P1B11-Rh.…”

Postnatal serum concentrations of endogenous free fatty acids in newborns admitted to the neonatal intensive care unit: effects on unbound bilirubin

“…31,32 Although the impact of endogenous FFA has not been assessed directly, increased FFA has bilirubin displacing effects, especially in premature newborns receiving intravenous lipid supplementation for nutrition and growth. 7,9,10,28,33 At an FFA/Alb ratio 54, FFAs compete with bilirubin at the bilirubin binding site, resulting in the displacement of bilirubin. 7,8,10,27,28 We found that endogenous FFAs did not affect Alb binding of bilirubin, resulting in elevations of UB, since none of the sera, from both term and preterm infants, had FFA/Alb ratios 54.…”

“…[1][2][3][4][5] Serum UB concentrations depend not only on serum TB and Alb concentrations, but on the bilirubin-albumin binding affinity and the presence of displacers like free fatty acids (FFAs). [6][7][8][9][10] FFAs affect bilirubin-albumin binding. Briefly, Alb contains a primary high-affinity site for bilirubin and a secondary low-affinity site.…”

“…11,12 Indeed, intralipid therapy, which increases serum FFA concentrations, also increases serum UB concentrations in premature newborns of gestational age (GA) 4 28 weeks. 9,10 Serum FFAs can be increased not only by exogenous lipid emulsions, but by endogenous fasting and stress conditions. [13][14][15][16] The neonatal intensive care unit (NICU) admits sick newborns, including those with asphyxia and respiratory diseases, with stress during the early postnatal period.…”