Combined choline and DHA supplementation: a randomized controlled trial

Abstract

Objective Choline and docosahexaenoic acid (DHA) are essential nutrients for preterm infant development. They are metabolically linked via phosphatidylcholine (PC), a constitutive plasma membrane lipid and the major transport form of DHA in plasma. Plasma choline and DHA-PC concentrations rapidly decline after preterm birth. To improve preterm infant nutrition, we evaluated combined compared to exclusive choline and DHA supplementation, and standard feeding. Design Randomized partially blinded single-center trial. Setting Neonatal tertiary referral center in Tübingen, Germany. Patients 24 inborn preterm infants\u2009<\u200932 week postmenstrual age. Interventions Standard nutrition (control) or, additionally, enteral choline (30\xa0mg/kg/day), DHA (60\xa0mg/kg/day), or both for 10\xa0days. Single enteral administration of 3.6\xa0mg/kg [methyl-D 9 -] choline chloride as a tracer at 7.5\xa0days. Main outcome measures Primary outcome variable was plasma choline following 7 days of supplementation. Deuterated and unlabeled choline metabolites, DHA-PC, and other PC species were secondary outcome variables. Results Choline supplementation increased plasma choline to near-fetal concentrations [35.4 (32.8–41.7)\xa0µmol/L vs. 17.8 (16.1–22.4) µmol/L, p \u2009<\u20090.01] and decreased D 9 -choline enrichment of PC. Single DHA treatment decreased DHA in PC relative to total lipid [66 (60–68)% vs. 78 (74–80)%; p \u2009<\u20090.01], which was prevented by choline. DHA alone increased DHA-PC only by 35 (26–45)%, but combined treatment by 63 (49–74)% ( p \u2009<\u20090.001). D 9 -choline enrichment showed preferential synthesis of PC containing linoleic acid. PC synthesis via phosphatidylethanolamine methylation resulted in preferential synthesis of DHA-containing D 3 -PC, which was increased by choline supplementation. Conclusions 30\xa0mg/kg/day additional choline supplementation increases plasma choline to near-fetal concentrations, dilutes the D 9 -choline tracer via increased precursor concentrations and improves DHA homeostasis in preterm infants. Trial registration clinicaltrials.gov. Identifier: NCT02509728.