Choline metabolome response to prenatal choline supplementation across pregnancy: A randomized controlled trial

Abstract

Pregnancy places a unique stress upon choline metabolism, requiring adaptations to support both maternal and fetal requirements. The impact of pregnancy and prenatal choline supplementation on choline and its metabolome in free-living, healthy adults is relatively uncharacterized. This study investigated the effect of prenatal choline supplementation on maternal and fetal biomarkers of choline metabolism among free-living pregnant persons consuming self-selected diets. Participants were randomized to supplemental choline (as choline chloride) intakes of 550 mg/d (500 mg/d d0-choline + 50 mg/d methyl-d9-choline; intervention) or 25 mg/d d9-choline (control) from gestational week (GW) 12-16 until Delivery. Fasting blood and 24-h urine samples were obtained at study Visit 1 (GW 12-16), Visit 2 (GW 20-24), and Visit 3 (GW 28-32). At Delivery, maternal and cord blood and placental tissue samples were collected. Participants randomized to 550 (vs. 25) mg supplemental choline/d achieved higher (p < .05) plasma concentrations of free choline, betaine, dimethylglycine, phosphatidylcholine (PC), and sphingomyelin at one or more study timepoint. Betaine was most responsive to prenatal choline supplementation with increases (p ≤ .001) in maternal plasma observed at Visit 2-Delivery (relative to Visit 1 and control), as well as in the placenta and cord plasma. Notably, greater plasma enrichments of d3-PC and LDL-C were observed in the intervention (vs. control) group, indicating enhanced PC synthesis through the de novo phosphatidylethanolamine N-methyltransferase pathway and lipid export. Overall, these data show that prenatal choline supplementation profoundly alters the choline metabolome, supporting pregnancy-related metabolic adaptations and revealing biomarkers for use in nutritional assessment and monitoring during pregnancy.

Keywords: PEMT pathway; choline metabolome; phosphatidylcholine; pregnancy; prenatal choline supplementation.

FIGURE 1

The Impact of Intervention on the Water- and Lipid-Soluble Choline Metabolome Across Pregnancy. Pregnant persons were randomized to 550 versus 25 mg of choline supplementation throughout the 2nd and 3rd trimester of pregnancy. Choline, betaine, dimethylglycine, methionine, TMAO, phosphatidylcholine, sphingomyelin and lysophosphatidylcholine were measured via liquid chromatography tandem mass spectrometry in fasting plasma samples taken at Visit 1 (GW 12–16), Visit 2 (GW 20–24), and Visit 3 (GW 28–32), and in Delivery blood samples obtained at parturition. Metabolites were analyzed using mixed linear models to assess the impact of intervention; statistically significant differences between intervention groups at each time point are indicated with a *(p < .05; following Tukey’s Post-hoc Adjustment)