Pregnancy alters choline dynamics: results of a randomized trial using stable isotope methodology in pregnant and nonpregnant women

Am J Clin Nutr. 2013 Dec;98(6):1459-67. doi: 10.3945/ajcn.113.066092. Epub 2013 Oct 16.


Background: Although biomarkers of choline metabolism are altered by pregnancy, little is known about the influence of human pregnancy on the dynamics of choline-related metabolic processes.

Objective: This study used stable isotope methodology to examine the effects of pregnancy on choline partitioning and the metabolic activity of choline-related pathways.

Design: Healthy third-trimester pregnant (n = 26; initially week 27 of gestation) and nonpregnant (n = 21) women consumed 22% of their total choline intake (480 or 930 mg/d) as methyl-d9-choline for the final 6 wk of a 12-wk feeding study.

Results: Plasma d9-betaine:d9-phosphatidylcholine (PC) was lower (P ≤ 0.04) in pregnant than in nonpregnant women, suggesting greater partitioning of choline into the cytidine diphosphate-choline (CDP-choline) PC biosynthetic pathway relative to betaine synthesis during pregnancy. Pregnant women also used more choline-derived methyl groups for PC synthesis via phosphatidylethanolamine N-methyltransferase (PEMT) as indicated by comparable increases in PEMT-PC enrichment in pregnant and nonpregnant women despite unequal (pregnant > nonpregnant; P < 0.001) PC pool sizes. Pregnancy enhanced the hydrolysis of PEMT-PC to free choline as shown by greater (P < 0.001) plasma d3-choline:d3-PC. Notably, d3-PC enrichment increased (P ≤ 0.011) incrementally from maternal to placental to fetal compartments, signifying the selective transfer of PEMT-PC to the fetus.

Conclusions: The enhanced use of choline for PC production via both the CDP-choline and PEMT pathways shows the substantial demand for choline during late pregnancy. Selective partitioning of PEMT-PC to the fetal compartment may imply a unique requirement of PEMT-PC by the developing fetus.

Trial registration: NCT01127022.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Betaine / blood
  • Choline / administration & dosage
  • Choline / analogs & derivatives
  • Choline / blood
  • Choline / metabolism*
  • Deuterium
  • Diet*
  • Dietary Supplements*
  • Female
  • Fetal Blood
  • Humans
  • Hydrolysis
  • Maternal Nutritional Physiological Phenomena*
  • Maternal-Fetal Exchange*
  • Methylation
  • Phosphatidylcholines / blood
  • Phosphatidylethanolamine N-Methyltransferase / metabolism
  • Placenta / metabolism
  • Pregnancy / blood
  • Pregnancy / metabolism*
  • Pregnancy Trimester, Third
  • Young Adult


  • Phosphatidylcholines
  • methylcholine
  • Betaine
  • Deuterium
  • Phosphatidylethanolamine N-Methyltransferase
  • Choline

Associated data