PregnancyNCT02244684
Effects of Maternal Folate and Folic Acid Supplementation on DNA Methylation in the Newborn Infant
An observational study of Pregnancy and Maternal Nutrition, run by Unity Health Toronto at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 45 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Pregnancy, Maternal Nutrition, Fetal Health
- How many people
- 368 participants
- Where
- 1 siteCanada
- Study dates
- Sep 2010to Feb 2013
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Women only
- Healthy volunteers accepted
- Adult
Study population: Pregnant women were recruited from obstetrics clinics at St Michael's Hospital, a tertiary teaching hospital affiliated with the University of Toronto.
Who may be able to join
- singleton pregnancy
Who cannot join
- celiac disease
- Crohn's disease
- irritable bowel disease (IBD)
- gastric bypass surgery
- use of antifolate medications
- banking umbilical cord blood
Trial locations and contacts
1 site in 1 country.
About this study
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
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Pregnant women | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2014 (estimated)
- Study startSep 2010
- Primary completionFeb 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for PregnancyStudies of the same condition, open and under way.
- More trials run by Unity Health TorontoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 368 participants (actual)
Sponsor and investigators
- Lead sponsor
- Unity Health Toronto
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Young In Kim, Unity Health Toronto
- Investigators
- Young-In Kim, MD, Principal investigator, Unity Health TorontoDeborah O'Connor, RD, PhD, Principal investigator, The Hospital for Sick Children
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02244684
- Sponsor's protocol ID
- 10-246
- Status last verified
- Sep 2014
- First submitted
- 2 Sep 2014
- Last updated
- 19 Sep 2014
- Results posted
- No
Publications
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.
PubMed 31562504Visentin 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.
PubMed 27075906Plumptre 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.
PubMed 26269367Masih 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.
PubMed 26063067Visentin 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.
PubMed 25972528
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Maternal Folate and Folic Acid Supplementation on DNA Methylation in the Newborn Infant
- ClinicalTrials.gov ID
- NCT02244684
- Acronym / sponsor ID
- 10-246
- Conditions
- Pregnancy, Maternal Nutrition, Fetal Health, Epigenetics, Maternal B Vitamins
- Keywords
- Folate, Folic Acid, One-Carbon Nutrients, Epigenetics, Pregnancy, Fetal Health
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 368 participants (actual)
- Lead sponsor
- Unity Health TorontoUniversity, hospital or other
- Study start
- Sep 2010
- Primary completion
- Feb 2013 (actual)
- First posted
- 19 Sep 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pregnant women | – | – |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- Pregnant women were recruited from obstetrics clinics at St Michael's Hospital, a tertiary teaching hospital affiliated with the University of Toronto.
Key inclusion criteria (1 listed)
- singleton pregnancy
Key exclusion criteria (6 listed)
- celiac disease
- Crohn's disease
- irritable bowel disease (IBD)
- gastric bypass surgery
- use of antifolate medications
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Global CpG DNA methylation in umbilical cord blood lymphocytes determined by LC/MS-MS
Time frame: 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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2014.
- Derived from this study: PubMed 31562504Plumptre 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.
- Derived from this study: PubMed 27075906Visentin 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.
- Derived from this study: PubMed 26269367Plumptre 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.
- Derived from this study: PubMed 26063067Masih 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.
- Derived from this study: PubMed 25972528Visentin 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Young-In Kim, MD principal investigator
Unity Health Toronto
Deborah O'Connor, RD, PhD principal investigator
The Hospital for Sick Children
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Pregnancy and Maternal Nutrition, run by Unity Health Toronto at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Sep 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Global CpG DNA methylation in umbilical cord blood lymphocytes determined by LC/MS-MS (time frame: Day 1). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02244684, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2014.