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Folic Acid for the Prevention of Neural Tube Defects, Preventive Medication, 2017

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Recommendations: Preventive Medication for Folic Acid for the Prevention of Neural Tube Defects

Clinical Consideration:

Patient Population Under Consideration

This recommendation applies to women who are planning or capable of pregnancy. It does not apply to women who have had a previous pregnancy affected by neural tube defects or who are at very high risk due to other factors (e.g., use of certain antiseizure medications or family history). These women may be advised to take higher doses of folic acid.

Assessment of Risk

Although all women of childbearing age are at risk of having a pregnancy affected by neural tube defects and should take folic acid supplementation, some factors increase their risk, including a personal or family history (first- or second-degree relative) of neural tube defects.1 Women with a personal history of an affected pregnancy require special care and are not within the scope of this recommendation statement. Other risk factors include the use of particular antiseizure medications (e.g., valproic acid or carbamazepine), maternal diabetes, obesity, and mutations in folate-related enzymes.1

Questions persist regarding increased risk of neural tube defects in some racial/ethnic groups. Birth prevalence rates are highest among Hispanic women, followed by non-Hispanic white and non-Hispanic black women.1 Genetic mutations in folate-related enzymes may vary by race/ethnicity. Dietary folate or folic acid intake differs by race/ethnicity. For example, Mexican American women may be at increased risk because of decreased consumption of fortified foods and greater intake of corn masa–based diets.1 Fewer Hispanic women (28%) report consuming 0.4 mg (400 µg) or more of folic acid daily through fortified food or supplements, compared with 39% of non-Hispanic white women.15


Half of all pregnancies in the United States are unplanned.6 Therefore, clinicians should advise all women who are capable of pregnancy to take daily folic acid supplements. The critical period for supplementation starts at least 1 month before conception and continues through the first 2 to 3 months of pregnancy.178


Trials and observational studies conducted in settings without food fortification suggest that supplementation with a multivitamin containing 0.4 to 0.8 mg (400 to 800 µg) of folic acid decreases the risk of neural tube defects.178  Evidence shows that most women in the United States are not consuming fortified foods in a quantity needed to demonstrate optimal benefit.8 An analysis of NHANES data found that 48% of respondents of childbearing age consumed the recommended amount of folic acid from mandatorily fortified foods only.19

According to the National Academy of Sciences Food and Nutrition Board, the tolerable upper intake level of folic acid in women 19 years and older is 1 mg/d (1000 µg/d) from supplements or fortified food (excluding naturally occurring folate) and 0.8 mg/d (800 µg/d) for those aged 14 to 18 years.10 Fewer than 3% of girls and women aged 14 to 50 years receive more than 1 mg/d (1000 µg/d) of folic acid from supplements or food.31112

Additional Approaches to Prevention

The Community Preventive Services Task Force recommends community-wide education campaigns to encourage women of childbearing age to take folic acid supplements.13

In 2016, the US Food and Drug Administration approved folic acid fortification of corn masa flour. This allows manufacturers to voluntarily add folic acid to corn masa flour at levels consistent with those found in other enriched cereal grains.14


Other Considerations

Research Needs and Gaps


Study results on the effectiveness of folic acid supplementation in reducing neural tube defects among Hispanic women compared with white or black women have been inconsistent. Future research should continue to evaluate differences in diverse populations.1

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