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

Sponsor
Unity Health Toronto (Other)
Overall Status
Completed
CT.gov ID
NCT02244684
Collaborator
(none)
368
1

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase

    Study Design

    Study Type:
    Observational
    Actual Enrollment :
    368 participants
    Observational Model:
    Cohort
    Time Perspective:
    Prospective
    Study Start Date :
    Sep 1, 2010
    Actual Primary Completion Date :
    Feb 1, 2013

    Arms and Interventions

    Arm Intervention/Treatment
    Pregnant women

    Outcome Measures

    Primary Outcome Measures

    1. Global CpG DNA methylation in umbilical cord blood lymphocytes determined by LC/MS-MS [Day 1]

      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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 45 Years
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    Yes
    Inclusion Criteria:
    • singleton pregnancy
    Exclusion Criteria:
    • celiac disease

    • Crohn's disease

    • irritable bowel disease (IBD)

    • gastric bypass surgery

    • use of antifolate medications

    • banking umbilical cord blood

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 St. Michael's Hospital Toronto Ontario Canada M5B 1W8

    Sponsors and Collaborators

    • Unity Health Toronto

    Investigators

    • Principal Investigator: Young-In Kim, MD, Unity Health Toronto
    • Principal Investigator: Deborah O'Connor, RD, PhD, The Hospital for Sick Children

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Young In Kim, Senior Scientist, Unity Health Toronto
    ClinicalTrials.gov Identifier:
    NCT02244684
    Other Study ID Numbers:
    • 10-246
    First Posted:
    Sep 19, 2014
    Last Update Posted:
    Sep 19, 2014
    Last Verified:
    Sep 1, 2014
    Keywords provided by Young In Kim, Senior Scientist, Unity Health Toronto

    Study Results

    No Results Posted as of Sep 19, 2014