Understanding Effects of Folic Acid on the Methylosome and Transcriptome of Women With Spina Bifida Affected Pregnancies

Study Overview
=================
Brief Summary
-----------------
Folic acid is currently considered to be the standard of care for primary and secondary prevention of spina bifida, but the mechanisms underlying folic acid's benefits are unknown. One hypothesis is that folic acid changes DNA methylation and transcription of genes important in neural tube closure. In this study, the investigators will evaluate how DNA methylation of genes associated with neural tube closure changes after a short course of standard-of-care folic acid supplementation. In addition, the investigators will assess whether environmental arsenic exposure modifies the effects of folic acid on the methylosome.

Detailed Description
-----------------
The investigators will encourage women who have recently had a pregnancy affected by spina bifida to take daily folic acid supplements for three months. Folic acid supplementation is considered standard of care for primary and secondary prevention of spina bifida. The investigators will compare DNA methylation in blood and folate levels before and after folic acid use.

Official Title
-----------------
Understanding Effects of Folic Acid on the Methylosome and Transcriptome of Women With Spina Bifida Affected Pregnancies

Conditions
-----------------
Pregnancy; Spina Bifida, Fetal, Environmental Exposure

Intervention / Treatment
-----------------
* Dietary Supplement: Folic Acid Tablet


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Women (18+) with a prior pregnancy affected by spina bifida Available for required study visits Exclusion Criteria: Personal history of diabetes or gestational diabetes Current anticonvulsant medication use History of pregnancy affected by identified genetic syndrome associated with neural tube defect such as Trisomy 18 Current pregnancy Abnormal peripheral blood film results (suggestive of megaloblastic anemia/B12 deficiency.)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Folic Acid<br>5 mg folic acid supplement by mouth once a day for 12 weeks | Dietary Supplement: Folic Acid Tablet<br>* 5 mg folic acid supplement<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in DNA Methylation patterns | The investigators will use DNA methylation arrays to compare methylation patterns before and after course of folic acid. | Week 1 and Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in serum folate concentration | Chemiluminescent Microparticle Immunoassay will be used to measure folate concentration. The investigators will assess changes in serum folate concentration before and after folic acid use. | Week 1 and Week 12 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Spina Bifida, Folic Acid, DNA Methylation, arsenic