USPSTF: Benefits of Folic Acid in Pregnancy Still Substantial

pregnancy vitamins
pregnancy vitamins
The review found that there is substantial evidence that supports folic acid supplementation during pregnancy.

A statement published in JAMA by the US Preventive Services Task Force (USPSTF) indicates that the benefits of folic acid supplementation, first recommended in 1992 for the prevention of neural tube defects (NTDs) during pregnancy, are still substantial, and that current evidence shows minimal potential harm to the mother or fetus.1,2

The original USPSTF recommendation came in response to a finding from a 1991 study that showed that NTDs were reduced by more than 50% in women who took folic acid supplements prior to conception.3  The initial dose recommendation in 1992 was 400 μg/d, which was expanded in 2009 to 400 to 800 μg/d.4  According to an accompanying editorial in the same 2016 issue of JAMA by James Mills, MD, supplementation, when combined with the mandated fortification of all enriched cereal grains instituted in the United States in 1996, has resulted in significant reduction in NTD rates.5,6

The current revised evidence report and systematic review of literature conducted for the USPSTF1 evaluated 24 studies of folic acid supplementation published from 1984 to January of 2016. The reviewers identified 32 good-quality or fair-quality articles from a total of 5786 that provided results of primary studies or systematic reviews. 

Twenty publications demonstrated clear benefits of folic acid supplementation, capturing case-controlled data from 8 data sources that reported on births occurring from 1976 to 2007 (including the Hungarian trial,7-12,13 the Hungarian cohort,14 the National Birth Defects Prevention Study,15,16 the Slone Birth Defects Study,17-19 the National Institute of Child Health and Human Development [NICHD] Neural Tube Defects Study,20 the New England study,21,22 the California Birth Defects Monitoring Program,22 and the Texas Department of Health’s Neural Tube Defect Project23). One of the most significant randomized clinical trials was conducted in Hungary with 5453 women from 1984 to 1992. This study reported 6 cases of NTDs in women who had not taken supplementation compared with no cases in the group who did.7-11

The second issue opened to review was whether there was evidence of increased risk associated with folic acid supplementation. Both the Hungarian trial and one prospective cohort study demonstrated no statistically significant increase in the risk of twin births associated with supplementation.10,25 Other risks for asthma, wheezing, and allergy were evaluated in 3 studies that failed to show consistent evidence of a link to folic acid supplementation.26-28

The authors pointed out that a potential factor in the limited risk of harm from supplementation is that so few women exceed the upper limits of dosing; the 2015 Dietary Guideline Advisory Committee reported that less than 3% of women between the ages of 14 and 50 years had a daily intake of more than 1000 μg/d from combined food and supplementation sources.29

As neural tube defects appear by the 28th day of pregnancy (when the neural tube closes), the current updated USPSTF recommendations targeted women who are “planning or capable of pregnancy,” suggesting dosages of 400 to 800 μg/d.2 These recommendations were extended to all women of childbearing years. 2


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