Combined choline and DHA supplementation: a randomized controlled trial. 
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.  Randomized partially blinded single-center trial.  Neonatal tertiary referral center in Tübingen, Germany.  24 inborn preterm infants < 32 week postmenstrual age.  Standard nutrition (control) or, additionally, enteral choline (30 mg/kg/day), DHA (60 mg/kg/day), or both for 10 days.  Single enteral administration of 3.6 mg/kg [methyl-D9-] choline chloride as a tracer at 7.5 days.  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.  Choline supplementation increased plasma choline to near-fetal concentrations [35.4 (32.8-41.7) µmol/L vs. 17.8 (16.1-22.4) µmol/L, p < 0.01] and decreased D9-choline enrichment of PC.  Single DHA treatment decreased DHA in PC relative to total lipid [66 (60-68)% vs. 78 (74-80)%; p < 0.01], which was prevented by choline.  DHA alone increased DHA-PC only by 35 (26-45)%, but combined treatment by 63 (49-74)% (p < 0.001).  D9-choline enrichment showed preferential synthesis of PC containing linoleic acid.  PC synthesis via phosphatidylethanolamine methylation resulted in preferential synthesis of DHA-containing D3-PC, which was increased by choline supplementation.  30 mg/kg/day additional choline supplementation increases plasma choline to near-fetal concentrations, dilutes the D9-choline tracer via increased precursor concentrations and improves DHA homeostasis in preterm infants.  clinicaltrials.gov.  Identifier: NCT02509728.