Phototherapy Alters the Plasma Metabolite Profile in Infants Born Preterm with Hyperbilirubinemia

Abstract

To investigate the effects of gestational age (GA) and phototherapy on the plasma metabolite profile of preterm infants with neonatal hyperbilirubinemia (NHB). From a cohort of prospectively enrolled infants born preterm (n=92), plasma samples of very preterm (VPT; GA, 28+0 to 31+6weeks, n=27) and moderate/late preterm (M/LPT; GA, 32+0 to 35+6weeks, n=33) infants requiring phototherapy for NHB were collected prior to the initiation of phototherapy and 24hours after starting phototherapy. An additional sample was collected 48hours after starting phototherapy in a randomly selected subset (n=30; VPT n=15; M/LPT n=15). Metabolite profiles were determined using ultraperformance liquid chromatography tandem mass spectroscopy. Two-way ANCOVA was used to identify metabolites that differed between GA groups and timepoints after adjusting for total serum bilirubin levels (false discovery rate q-value < 0.05). Top impacted pathways were identified using pathway over-representation analysis. Phototherapy was initiated at lower total serum bilirubin (mean±SD mg/dL) levels in VPT compared with M/LPT infants (7.3±1.4 vs 9.9±1.9, P<.01). We identified 664 metabolites that were significant for a phototherapy effect, 191 metabolites significant for GA, and 46 metabolites significant for GA×phototherapy interaction (false discovery rate q-value < 0.05). Longer duration phototherapy had a larger mean effect size (24hours postphototherapy: d=0.36; 48hours postphototherapy: d=0.43). Top pathways affected by phototherapy included membrane lipid metabolism, one-carbon metabolism, creatine biosynthesis, and oligodendrocyte differentiation. Phototherapy alters the plasma metabolite profile more than GA in preterm infants with NHB, affecting pathways related to lipid and one-carbon metabolism, energy biosynthesis, and oligodendrocyte differentiation.