title: Maternal Choline Status, but Not Fetal Genotype, Influences Cord Plasma Choline Metabolite Concentrations.
abstract: BACKGROUND
  Choline deficiency during pregnancy can lead to adverse birth outcomes, including impaired neurodevelopment and birth defects. Genetic variants of choline and one-carbon metabolism may also influence birth outcomes by altering plasma choline concentrations. The effects of maternal ad libitum choline intake during pregnancy and fetal genetic variants on maternal and cord concentrations of choline and its metabolites are unknown.
  
  
  OBJECTIVE
  This prospective study sought to assess the effect of 1) maternal dietary choline intake on maternal and cord plasma concentrations of choline and its metabolites, and 2) fetal genetic polymorphisms on cord plasma concentrations.
  
  
  METHODS
  The dietary choline intake of 368 pregnant Canadian women was assessed in early (0-16 wk) and late (23-37 wk) pregnancy with the use of a food frequency questionnaire. Plasma concentrations of free choline and its metabolites were measured in maternal samples at recruitment and delivery, and in the cord blood. Ten fetal genetic variants in choline and one-carbon metabolism were assessed for their association with cord plasma concentrations of free choline and its metabolites.
  
  
  RESULTS
  Mean maternal plasma free choline, dimethylglycine, and trimethylamine N-oxide (TMAO) concentrations increased during pregnancy by 49%, 17%, and 13%, respectively (P < 0.005), whereas betaine concentrations decreased by 21% (P < 0.005). Cord plasma concentrations of free choline, betaine, dimethylglycine, and TMAO were 3.2, 2.0, 1.3, and 0.88 times corresponding maternal concentrations at delivery, respectively (all P < 0.005). Maternal plasma concentrations of betaine, dimethylglycine, and TMAO (r(2) = 0.19-0.51; P < 0.0001) at delivery were moderately strong, whereas maternal concentrations of free choline were not significant (r(2) = 0.12; P = 0.06), predictors of cord plasma concentrations of these metabolites. Neither maternal dietary intake nor fetal genetic variants predicted maternal or cord plasma concentrations of choline and its metabolites.
  
  
  CONCLUSIONS
  These data collectively indicate that maternal choline status, but not fetal genotype, influences cord plasma concentrations of choline metabolites. This trial was registered at clinicaltrials.gov as NCT02244684.
authors.affiliation: Department of Nutritional Sciences, University of Toronto, Toronto, Canada; Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, Canada;
authors.forename: Carly E
authors.initials: CE
authors.lastname: Visentin
authors.affiliation: Department of Nutritional Sciences, University of Toronto, Toronto, Canada; Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, Canada;
authors.forename: Shannon
authors.initials: S
authors.lastname: Masih
authors.affiliation: Department of Nutritional Sciences, University of Toronto, Toronto, Canada; Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, Canada;
authors.forename: Lesley
authors.initials: L
authors.lastname: Plumptre
authors.affiliation: Division of Nutritional Sciences, College of Human Ecology, Cornell University, Ithaca, NY; and.
authors.forename: Olga
authors.initials: O
authors.lastname: Malysheva
authors.affiliation: Department of Nutritional Sciences, University of Toronto, Toronto, Canada;
authors.forename: Daiva E
authors.initials: DE
authors.lastname: Nielsen
authors.affiliation: Departments of Medicine and Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, Canada;
authors.forename: Kyoung-Jin
authors.initials: KJ
authors.lastname: Sohn
authors.affiliation: Departments of Medicine and Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, Canada;
authors.forename: Anna
authors.initials: A
authors.lastname: Ly
authors.affiliation: Obstetrics and Gynecology, St. Michael's Hospital and University of Toronto, Toronto, Canada;
authors.forename: Andrea Y
authors.initials: AY
authors.lastname: Lausman
authors.affiliation: Obstetrics and Gynecology, St. Michael's Hospital and University of Toronto, Toronto, Canada;
authors.forename: Howard
authors.initials: H
authors.lastname: Berger
authors.affiliation: freelance statistics consultant, Toronto, Canada.
authors.forename: Ruth
authors.initials: R
authors.lastname: Croxford
authors.affiliation: Department of Nutritional Sciences, University of Toronto, Toronto, Canada;
authors.forename: Ahmed
authors.initials: A
authors.lastname: El-Sohemy
authors.affiliation: Division of Nutritional Sciences, College of Human Ecology, Cornell University, Ithaca, NY; and.
authors.forename: Marie A
authors.initials: MA
authors.lastname: Caudill
authors.affiliation: Department of Nutritional Sciences, University of Toronto, Toronto, Canada; Research Institute, the Hospital for Sick Children, Toronto, Canada;
authors.forename: Deborah L
authors.initials: DL
authors.lastname: O'Connor
authors.affiliation: Department of Nutritional Sciences, University of Toronto, Toronto, Canada; Departments of Medicine and Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, Canada; youngin.kim@utoronto.ca.
authors.forename: Young-In
authors.initials: YI
authors.lastname: Kim
mesh_terms: D000293:Adolescent; D000328:Adult; D001622:Betaine / Q000097:blood; D002170:Canada; D002794:Choline / Q000097:blood*; D005260:Female; D005312:Fetal Blood / Q000737:chemistry*; D005333:Fetus; D005838:Genotype; D064368:Healthy Volunteers; D006801:Humans; D039382:Maternal Nutritional Physiological Phenomena; D008744:Methylamines / Q000097:blood; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011446:Prospective Studies; D012521:Sarcosine / Q000031:analogs & derivatives / Q000097:blood; D011795:Surveys and Questionnaires; D055815:Young Adult
chemical_list: D008744:Methylamines; D001622:Betaine; C025138:dimethylglycine; C005855:trimethyloxamine; D002794:Choline; D012521:Sarcosine
keywords: betaine; choline; dimethylglycine; fetal genotype; maternal diet; pregnancy; trimethylamine N-oxide