Folic acid supplementation for the prevention of neural tube defects: an update of the evidence for the U.S. Preventive Services Task Force

Ann Intern Med. 2009 May 5;150(9):632-9. doi: 10.7326/0003-4819-150-9-200905050-00010.


Background: Neural tube defects (NTDs) are among the most common birth defects in the United States. In 1996, the U.S. Preventive Services Task Force (USPSTF) recommended that all women planning a pregnancy or capable of conception take a supplement containing folic acid to reduce the risk for NTDs.

Purpose: To search for new evidence published since 1996 on the benefits and harms of folic acid supplementation for women of childbearing age to prevent neural tube defects in offspring, to inform an updated USPSTF recommendation.

Data sources: MEDLINE and Cochrane Central Register of Controlled Trials searches from January 1995 through December 2008, recent systematic reviews, reference lists of retrieved articles, and expert suggestions.

Study selection: English-language randomized, controlled trials; cohort studies; case-control studies; systematic reviews; and meta-analyses were selected if they provided information on the benefits and harms of folic acid supplementation in women of childbearing age to reduce NTDs in offspring.

Data extraction: All studies were reviewed, abstracted, and rated for quality by using predefined USPSTF criteria.

Data synthesis: Four observational studies reported benefit of reduction of risk for NTDs 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 adjustment for in vitro fertilization and underreporting of folic acid intake.

Limitations: The evidence on dose was limited. No evidence was found on the potential harm of masking vitamin B(12) deficiency in women of childbearing age. The search focused on the association of NTDs with supplementation only and therefore does not provide a comprehensive review of the effects of folic acid on all possible outcomes or of the effects of dietary intake of folic acid.

Conclusion: New observational evidence supports previous evidence from a randomized, controlled trial that folic acid-containing supplements reduce the risk for NTD-affected pregnancies. The association of folic acid use with twin gestation may be confounded by fertility interventions.

Publication types

  • Review

MeSH terms

  • Dietary Supplements* / adverse effects
  • Evidence-Based Medicine
  • Female
  • Folic Acid / administration & dosage*
  • Folic Acid / adverse effects
  • Humans
  • Neural Tube Defects / prevention & control*
  • Pregnancy
  • Risk Assessment
  • Vitamins / administration & dosage


  • Vitamins
  • Folic Acid