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Folic Acid Supplementation for the Prevention of Neural Tube Defects

An Update of the Evidence for the U.S. Preventive Services Task Force

Evidence Syntheses, No. 70

Tracy Wolff, MD, MPH, Catherine Takacs Witkop, MD, MPH, Therese Miller, DrPH, and Shamsuzzoha B Syed, MD, MPH, DPH(Cantab).

Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services, 540 Gaither Road, Rockville, MD 20850
Rockville (MD): Agency for Healthcare Research and Quality (US); 2009 May.
Report No.: 09-05132-EF-1
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Structured Abstract

Background:

Neural tube defects (NTDs) are among the most common birth defects in the United States.

Purpose:

To update the evidence on folic acid supplementation in women of childbearing age for the prevention of neural tube defects in their offspring.

Data Sources:

MEDLINE and Cochrane Library searches (from January 1995 through November 2007), recent systematic reviews, reference lists of retrieved articles, and expert suggestions.

Study Selection:

English language studies were selected to answer the following two questions: Does folic acid supplementation in women of childbearing age reduce the risk of a pregnancy affected by a neural tube defect? Does folic acid supplementation in women of childbearing age increase the risk of any harmful outcomes for either the woman or the infant? The following study types were selected: for potential benefits of folic acid—randomized, controlled trials (RCTs), case-control studies, cohort studies, systematic reviews and meta-analyses; for potential harms of folic acid—RCTs, case-control studies, systematic reviews, meta-analyses, and large observational studies.

Data Extraction:

All studies were reviewed, abstracted, and rated for quality using predefined U.S. Preventive Services Task Force criteria.

Data Synthesis:

Four observational studies reported benefit, in reduction of risk of NTD associated with folic acid-containing supplements. Differences in study type and methods prevent the calculation of a summary of the reduction in risk. The one included study on harms reported that the association of twinning with folic acid intake disappeared after adjusting for in vitro fertilization and for underreporting of folic acid intake.

Limitations:

There is limited evidence on dose. We found no evidence on the potential harm of masking vitamin B12 deficiency in women of childbearing age. Our search focused on NTDs and therefore does not provide a comprehensive review of the effects of folic acid on all possible outcomes.

Conclusions:

New observational evidence supports previous RCT evidence that folic acid-containing supplements reduce the risk of NTD-affected pregnancies. The association of folic acid use with twin gestation may be confounded by fertility interventions including ovulation stimulation and in vitro fertilization.

Suggested citation:

Wolff T, Witkop CT, Miller T, Syed SB. Folic Acid Supplementation for the Prevention of Neural Tube Defects: An Update of the Evidence for the U.S. Preventive Services Task Force. Evidence Synthesis No. 70. AHRQ Publication No. 09-051132-EF-1. Rockville, Maryland: Agency for Healthcare Research and Quality. May 2009.

This report is based on research conducted by staff of the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD. The investigators involved have declared no conflicts of interest with objectively conducting this research. The findings and conclusions in this document are those of the authors, who are responsible for its content, and do not necessarily represent the views of AHRQ. No statement in this report should be construed as an official position of AHRQ or of the U.S. Department of Health and Human Services.

The information in this report is intended to help clinicians, employers, policymakers, and others make informed decisions about the provision of health care services. This report is intended as a reference and not as a substitute for clinical judgment.

This report may be used, in whole or in part, as the basis for the development of clinical practice guidelines and other quality enhancement tools, or as a basis for reimbursement and coverage policies. AHRQ or U.S. Department of Health and Human Services endorsement of such derivative products may not be stated or implied.

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