Recommendation Reaffirmed for Folic Acid Supplementation to Prevent Birth Defects

Folic acid is a dietary supplement that contains a form of folate (vitamin B9).[1] Persons planning to or who could become pregnant and who do not consume adequate amounts of folate are at risk of having babies with congenital neural tube defects. These defects entail malformations of the brain, skull, spine or overlying tissues (such as spina bifida, a condition in which part of the spinal cord protrudes through an opening in the back).

Prevention of neural tube defects is important because they tend to be severe, and their treatment usually is limited.[2] These defects also can cause death or varying degrees of disability (including weakness or paralysis, and bladder or bowel problems) among affected babies and children.

In 2009 and 2017, the U.S. Preventive Services Task Force (USPSTF) — a federally funded, independent, voluntary panel of experts that makes evidence-based recommendations about the effectiveness of specific preventive-care services for patients — recommended that all women who are planning or capable of pregnancy take a daily folic acid supplement.[3]

After commissioning an updated evidence review of the benefits and risks of folic acid supplementation for reducing the risk of neural tube defects in the babies of persons who are capable of becoming pregnant, the USPSTF reaffirmed this recommendation.[4],[5] The USPSTF recommendation statement and evidence review were published in JAMA in August 2023.

About folate[6]

All body cells need folate to make DNA and other genetic material. Folate is naturally present in beef liver and many foods, such as vegetables (especially asparagus, brussels sprouts and dark green leafy vegetables [including spinach and mustard green]), fruits and fruit juices (especially oranges and orange juice), nuts, beans and peas. People who regularly consume a variety of these natural foods can get enough folate from them.

Additionally, food manufacturers add folic acid — a type of folate — to enriched breads, cereals, corn meals, flours, pastas, rice and other grain, as required by the Food and Drug Administration.

The recommended daily intake for folate varies by life stage and is the highest during pregnancy (see Table for details).

Table: Average Recommended Daily Folate Intakes

Abbreviations: mcg DFE, micrograms of dietary folate equivalents
Source: National Institutes of Health, Office of Dietary Supplements, Folate Fact Sheets for Consumers

The updated USPSTF evidence review and recommendation[7],[8]

In 2017, the USPSTF found convincing evidence supporting the benefits of folic acid supplementation among women who are planning or capable of pregnancy to prevent neural tube defects in their offspring. For example, a 1992 Hungarian randomized clinical trial assigned approximately 4,700 women without a history of pregnancy affected by neural tube defects to receive either a vitamin supplement that contained folic acid or a trace-element supplement in the periconceptional period.[9] This trial found no cases of neural tube defects in the offspring of the folic acid treated women compared with six cases in the other group, a difference that was statistically significant.

The USPSTF also found adequate evidence in 2017 that folic acid supplementation at usual doses in women who are planning or capable of pregnancy is not associated with serious harms. Therefore, the USPSTF concluded with high certainty that the benefit of folic acid supplementation to prevent neural tube defects substantially outweighs the harms.

In its review of new evidence since 2017, the USPSTF identified three observational studies that provided additional support for the benefit of folic acid supplementation before or during pregnancy to prevent neural tube defects in the offspring. It also found nine new observational studies that showed no significant harm associated with folic acid supplementation in terms of autism among offspring, cancer in pregnant persons or multiple gestation (pregnancy with more than one baby at a time).

Therefore, the USPSTF reaffirmed its previous recommendation, with high certainty, that all persons who are planning to or could become pregnant take a daily supplement containing 400 to 800 micrograms (mcg) of folic acid starting at least one month before conception and continuing through the end of the first trimester of pregnancy.

The reason that consuming folic acid supplementation should start at least one month before conception is because the neural plate in the fetus completes its formation early during pregnancy (usually 26 to 28 days after conception). Therefore, supplementation at this time is critical to decrease the risk of neural tube defects.

Unfortunately, survey studies show that, at best, 40% of recently pregnant women or those trying to get pregnant reported taking folic acid supplements during the period from before conception to early pregnancy, as applicable.[10] Also, women who had an unintended pregnancy are up to five times less likely to have taken a folic acid supplement. Therefore, wide-scale implementation of the USPSTF recommendation in these persons will be critical to lowering the rate of neural tube defects in the U.S.

What You Can Do

If you are planning to or capable of becoming pregnant, take a 400 to 800 mcg folic acid supplement, starting at least one month prior to conception until the end of the first trimester of pregnancy.[11] Generally, these folic acid doses are included in prenatal multivitamins.

Discuss with your clinician if you are at a high risk of conceiving a baby with neural tube defects due to certain factors — such as if you had a previous pregnancy affected by neural tube defects, have a family history of neural tube defects or if you are taking certain medications that block folate action in the body — because you may need to take high folic acid doses. Examples of the medications that block folic acid action include methotrexate (JYLAMVO, OTREXUP, RASUVO, REDITREX, TREXALL, XATMEP, and generics), which is used to treat the autoimmune diseases rheumatoid arthritis and psoriasis, and seizure medications (such as phenytoin [DILANTIN, PHENYTEK, and generics]).

Also, if you have a condition that affects absorption of nutrients, such as celiac disease or inflammatory bowel disease, you may need a higher dose of folic acid.

It is important to consume a well-balanced nutritious diet or take a prenatal multivitamin supplement to ensure that you obtain adequate amounts of various essential nutrients, not just folic acid.
 

References

[1] National Institutes of Health, Office of Dietary Supplements. Folate fact sheet for consumers. Updated November 1, 2022. https://ods.od.nih.gov/factsheets/Folate-Consumer. Accessed November 27, 2023.

[2] Jin J. Folic acid to prevent neural tube defects. JAMA. 2023;330(5):480.

[3] US Preventive Services Task Force. Folic acid supplementation for the prevention of neural tube defects: US Preventive Services Task Force recommendation statement. JAMA. 2017;317(2):183-189.

[4] US Preventive Services Task Force. Folic acid supplementation to prevent neural tube defects: US Preventive Services Task Force reaffirmation recommendation statement. JAMA. 2023;330(5):454-459.

[5] Viswanathan M, Urrutia RP, Hudson KN, et al. Folic acid supplementation to prevent neural tube defects: Updated evidence report and systematic review for the US Preventive Services Task Force. JAMA. 2023;330(5):460-466.

[6] National Institutes of Health, Office of Dietary Supplements. Folate fact sheet for consumers. Updated November 1, 2022. https://ods.od.nih.gov/factsheets/Folate-Consumer. Accessed November 27, 2023.

[7] Viswanathan M, Urrutia RP, Hudson KN, et al. Folic acid supplementation to prevent neural tube defects: Updated evidence report and systematic review for the US Preventive Services Task Force. JAMA. 2023;330(5):460-466.

[8] US Preventive Services Task Force. Folic acid supplementation to prevent neural tube defects: US Preventive Services Task Force reaffirmation recommendation statement. JAMA. 2023;330(5):454-459.

[9] Czeizel AE, Dudás I. Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. N Engl J Med. 1992;327(26):1832-1835.

[10] Viswanathan M, Urrutia RP, Hudson KN, et al. Folic acid supplementation to prevent neural tube defects: A limited systematic review update for the US Preventive Services Task Force. Evidence synthesis No. 230. Agency for Healthcare Research and Quality;2023. AHRQ publication 22-05302-EF-1

[11] Jin J. Folic acid to prevent neural tube defects. JAMA. 2023;330(5):480.