Effects of Maternal Folate and Folic Acid Supplementation on DNA Methylation in the Newborn Infant

NCT02244684 | Completed

• 1 other identifier: 10-246
• Study Type: observational
• Target: 368
• Locations: 1 country
• Sites: 1

Brief Summary

An overwhelming body of evidence of the protective effect of folic acid supplementation on neural tube defect affected pregnancies led to mandatory folic acid fortification in Canada in 1998. Folate is an important co-factor in the transfer of one-carbon units essential in DNA synthesis, repair, and methylation reactions, aberrations of which have been implicated in the pathogenesis of several chronic diseases including cancer. Epigenetic reprogramming occurs in utero and has the potential to be modulated by the methyl donor supply of which folate is a contributor. Animal studies have shown maternal folate exposure can modulate epigenetic changes in the offspring, however, there is limited evidence of this relationship in humans. The aim of this research is to determine the effects of maternal dietary folate and supplemental folic acid intake during the periconceptional and in utero periods on global and gene-specific DNA methylation in human infants. This is a prospective observational study involving 368 Canadian mother-child pairs recruited from St. Michael's Hospital in Toronto, Ontario. Dietary and demographical information was collected from consenting pregnant women at study baseline (12-16 weeks gestation) and in the third trimester (34-37 weeks gestation). Maternal blood samples were obtained at baseline and prior to delivery and a sample of umbilical cord blood was collected at parturition to measure levels of folate status. Global and gene-specific DNA methylation in umbilical cord blood will be correlated with cord and maternal folate status. The data will be analyzed using separate ordinary least squares (OLS) regressions. Results from this study will contribute to a better understanding of how maternal folate and folic acid intake can modulate epigenetic modifications in the offspring and potentially have an effect on disease susceptibility later in life.

Conditions

Pregnancy; Maternal Nutrition; Fetal Health; Epigenetics; Maternal B Vitamins

Keywords

Folate; Folic Acid; One-Carbon Nutrients; Epigenetics; Pregnancy; Fetal Health

Outcome Measures

Primary Outcomes (1)

• Global CpG DNA methylation in umbilical cord blood lymphocytes determined by LC/MS-MS

  Maternal dietary intake and supplemental use and blood levels of folate/folic acid and other one carbon nutrients in early and late pregnancy will be correlated with global CpG DNA methylation in umbilical cord blood lymphocytes

  Day 1

Study Arms (1)

Pregnant women

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Pregnant women were recruited from obstetrics clinics at St Michael's Hospital, a tertiary teaching hospital affiliated with the University of Toronto.

You may qualify if:

• singleton pregnancy

You may not qualify if:

• celiac disease
• Crohn's disease
• irritable bowel disease (IBD)
• gastric bypass surgery
• use of antifolate medications
• banking umbilical cord blood

Sponsors & Collaborators

• Unity Health Toronto: lead

Study Sites (1)

St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

Related Publications (5)

• Plumptre L, Tammen SA, Sohn KJ, Masih SP, Visentin CE, Aufreiter S, Malysheva O, Schroder TH, Ly A, Berger H, Croxford R, Lamers Y, Caudill MA, Choi SW, O'Connor DL, Kim YI. Maternal and Cord Blood Folate Concentrations Are Inversely Associated with Fetal DNA Hydroxymethylation, but Not DNA Methylation, in a Cohort of Pregnant Canadian Women. J Nutr. 2020 Feb 1;150(2):202-211. doi: 10.1093/jn/nxz232.

  PMID: 31562504 DERIVED

• Visentin CE, Masih SP, Plumptre L, Schroder TH, Sohn KJ, Ly A, Lausman AY, Berger H, Croxford R, Lamers Y, Kim YI, O'Connor DL. Low Serum Vitamin B-12 Concentrations Are Prevalent in a Cohort of Pregnant Canadian Women. J Nutr. 2016 May;146(5):1035-42. doi: 10.3945/jn.115.226845. Epub 2016 Apr 13.

  PMID: 27075906 DERIVED

• Plumptre L, Masih SP, Ly A, Aufreiter S, Sohn KJ, Croxford R, Lausman AY, Berger H, O'Connor DL, Kim YI. High concentrations of folate and unmetabolized folic acid in a cohort of pregnant Canadian women and umbilical cord blood. Am J Clin Nutr. 2015 Oct;102(4):848-57. doi: 10.3945/ajcn.115.110783. Epub 2015 Aug 12.

  PMID: 26269367 DERIVED

• Masih SP, Plumptre L, Ly A, Berger H, Lausman AY, Croxford R, Kim YI, O'Connor DL. Pregnant Canadian Women Achieve Recommended Intakes of One-Carbon Nutrients through Prenatal Supplementation but the Supplement Composition, Including Choline, Requires Reconsideration. J Nutr. 2015 Aug;145(8):1824-34. doi: 10.3945/jn.115.211300. Epub 2015 Jun 10.

  PMID: 26063067 DERIVED

• Visentin CE, Masih S, Plumptre L, Malysheva O, Nielsen DE, Sohn KJ, Ly A, Lausman AY, Berger H, Croxford R, El-Sohemy A, Caudill MA, O'Connor DL, Kim YI. Maternal Choline Status, but Not Fetal Genotype, Influences Cord Plasma Choline Metabolite Concentrations. J Nutr. 2015 Jul;145(7):1491-7. doi: 10.3945/jn.115.211136. Epub 2015 May 13.

  PMID: 25972528 DERIVED

Study Officials

• Young-In Kim, MD

  Unity Health Toronto

  PRINCIPAL INVESTIGATOR

• Deborah O'Connor, RD, PhD

  The Hospital for Sick Children

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Scientist

Study Record Dates

• First Submitted: September 2, 2014
• First Posted: September 19, 2014
• Study Start: September 1, 2010
• Primary Completion: February 1, 2013
• Last Updated: September 19, 2014

Record last verified: 2014-09

Locations

CA (1)