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

Study Overview
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Brief Summary
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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
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Pregnancy, Maternal Nutrition, Fetal Health, Epigenetics, Maternal B Vitamins

Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Pregnant women<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Folate, Folic Acid, One-Carbon Nutrients, Epigenetics, Pregnancy, Fetal Health