In This article

• There is strong evidence supporting the periconceptual use of folic acid to prevent neural tube defects.
• Folic acid supplementation should begin before conception, ideally at least one month before pregnancy, because neural tube development occurs very early in pregnancy.
• Because half of all pregnancies are unplanned, the USPSTF recommends 400–800 micrograms of folic acid daily for any person who could become pregnant, continuing through the first trimester. 
• There is preliminary research suggesting that folic acid may reduce the risk of autism and other neurodevelopmental disorders.
• The FASSTT randomized controlled trial found that 400 micrograms of folic acid during the second and third trimesters was associated with better cognitive outcomes in children at ages 3 and 7 years.

Folic Acid Awareness Week is a good time to discuss the basics of folic acid supplementation during pregnancy and, in particular, when supplementation should begin and how long it should continue. 

Folic acid supplementation before and during early pregnancy is one of the most well-established strategies for reducing the risk of neural tube defects (NTDs). But questions remain about when supplementation should begin and how long it should continue.

Current recommendations are relatively straightforward. The USPSTF recommends that all persons who are planning pregnancy or who could become pregnant take 400-800 micrograms (0.4-0.8 mg) of folic acid daily, beginning at least 1 month before conception and continuing through the first 2-3 months of pregnancy. This is an A-level recommendation. (USPSTF)

ACOG similarly recommends a prenatal vitamin containing at least 400 micrograms of folic acid, beginning at least one month before pregnancy and continuing through the first 12 weeks. During pregnancy, the recommended daily intake of folate increases to 600 micrograms. (ACOG)

The CDC currently recommends that all women capable of becoming pregnant obtain 400 micrograms of folic acid every day, whether or not they are actively planning a pregnancy. (CDC)

Why recommend supplementation when many foods are fortified with folic acid? Although food fortification has substantially increased folic acid intake in the United States, not everyone consumes enough fortified foods to obtain the amount needed for optimal prevention of NTDs. An analysis cited by the USPSTF found that only about half of women of reproductive age obtained the recommended amount of folic acid from fortified foods alone. In addition, folic acid from supplements has greater bioavailability than naturally occurring folate in food. (USPSTF)

There are important exceptions. Women with a previous pregnancy affected by an NTD are generally advised to take a much higher dose of folic acid (4 mg/day), beginning before conception and continuing through the first trimester. ACOG recommends beginning this higher dose at least 3 months before pregnancy. (ACOG)

Why Is Folic Acid So Important?

These recommendations are based on a substantial body of evidence demonstrating that folic acid supplementation around the time of conception reduces the risk of neural tube defects, including spina bifida and anencephaly. Randomized trials and systematic reviews have consistently demonstrated the preventive effect of folic acid on NTDs.

There is also evidence suggesting that periconceptional folic acid supplementation may reduce the risk of some other congenital anomalies, including congenital heart defects. A 2022 systematic review and meta-analysis of 37 studies found that periconceptional folic acid supplementation was associated with a lower risk of congenital heart defects, although the observational evidence is heterogeneous and further research is needed. 

The critical period for folic acid supplementation begins at least one month before conception and extends through the first 2–3 months of pregnancy. The early introduction of folic acid is recommended because the neural tube forms and closes very early in embryonic development, during the third and fourth weeks of pregnancy, often before a woman knows that she is pregnant. 

Timing Matters

Nearly half of pregnancies in the United States are unplanned. Consequently, recommending folic acid only to women who are actively trying to conceive will miss a substantial proportion of pregnancies. The USPSTF therefore recommends daily supplementation for all persons who could become pregnant, not only those who are pregnant or planning to conceive. (USPSTF)

The timing is biologically important. By the time a woman obtains a positive pregnancy test, neural tube formation may already have been completed. The neural tube typically completes its formation and closure approximately 26-28 days after fertilization. (USPSTF)

• Ideally, folic acid should be initiated at least one month before conception.
• Folic acid should continue through at least the first 12 weeks of pregnancy.
• If pregnancy occurs unexpectedly, folic acid should be started as soon as possible rather than assuming that it is too late to be beneficial.
• Women with a previous NTD-affected pregnancy or other indications for high-dose supplementation require individualized recommendations.

Folic Acid and Neurodevelopmental Disorders

There is increasing interest in whether folate has effects on the developing brain that extend beyond neural tube closure. Folate participates in one-carbon metabolism, nucleotide synthesis, and DNA methylation, processes that are particularly important during periods of rapid fetal development.

Several observational studies have reported associations between prenatal folic acid exposure and a lower risk of autism spectrum disorder (ASD) or other neurodevelopmental problems.

For example, in the Norwegian Mother and Child Cohort Study, which included more than 85,000 children, folic acid use from four weeks before conception through eight weeks after conception was associated with a lower risk of autistic disorder in children (adjusted OR 0.61; 95% CI, 0.41-0.90). 

Levine and colleagues subsequently observed that maternal use of folic acid and/or multivitamin supplements before pregnancy was associated with a lower likelihood of ASD in offspring compared with no supplementation before pregnancy (RR, 0.39; 95% CI, 0.30–0.50; P < .001). Maternal use of folic acid and/or multivitamin supplements during pregnancy was also associated with a lower likelihood of ASD in offspring compared with no supplementation during pregnancy (RR, 0.27; 95% CI, 0.22-0.33; P < .001). 

A 2021 meta-analysis including 10 studies and nearly 9,800 ASD cases found that folic acid supplementation during early pregnancy was associated with a lower risk of ASD (OR 0.57, 95% CI 0.41-0.78).

While these findings indicate that folic acid supplementation may have neurodevelopmental benefits, some studies have not shown beneficial effects.

It is important to recognize that these studies are not randomized controlled trials. The evidence is predominantly observational, and women who take prenatal vitamins may differ from those who do not in numerous ways that are difficult to completely control for, including health behaviors, socioeconomic factors, pregnancy planning, diet, access to medical care, and other variables.

For example, a prospective cohort study from Japan including almost 97,000 pregnancies found no significant association between folic acid supplementation before or during pregnancy and risk of ASD.

A 2025 umbrella review of 23 systematic reviews and meta-analyses concluded that maternal folic acid supplementation may reduce the risk of ASD, ADHD, and behavioral problems, but emphasized that much of the evidence is of low quality and that the observational nature of the evidence limits causal inference. 

While the evidence that folic acid prevents neural tube defects is strong, the evidence that it prevents autism or other neurodevelopmental disorders is promising but remains preliminary.

How Long Should Folic Acid Be Continued?

The standard NTD-prevention recommendations focus on the periconceptional period and first trimester. But the fetal brain continues to undergo substantial growth and differentiation throughout pregnancy and the early years of a child’s life. This raises an important question: Could continuing folic acid beyond the first trimester provide additional benefits?

There is emerging evidence suggesting that using folic acid throughout the pregnancy may have benefits.  In a randomized controlled trial conducted in Ireland, the Folic Acid Supplementation in the Second and Third Trimesters (FASSTT) study examined cognitive outcomes in children born to mothers who received either 400 micrograms of folic acid or placebo during the second and third trimesters of pregnancy. 

Of the 119 mother-child pairs enrolled in the study, 70 children completed the assessment at age 7 years and 39 completed the assessment at age 3 years. At age 7, children whose mothers had received folic acid scored significantly higher than those in the placebo group on a measure of word reasoning (mean 13.3 [95% CI, 12.4-14.2] vs. 11.9 [95% CI, 11.0-12.8]; P = .027). At age 3, children in the folic acid group also had significantly higher cognitive scores than those in the placebo group (mean 10.3 [95% CI, 9.3-11.3] vs. 9.5 [95% CI, 8.8-10.2]; P = .040).

The investigators also compared the children’s scores at age 7 with those from a nationally representative sample of British children. Children whose mothers had received folic acid had higher scores than the national sample on measures of verbal IQ (P < .001), performance IQ (P = .035), general language (P = .002), and full-scale IQ (P = .001). In comparison, children in the placebo group differed from the national sample only on verbal IQ (P = .034) and full-scale IQ (P = .017), with no significant differences in performance IQ or general language. These findings provide preliminary evidence that folic acid supplementation beyond the first trimester may have benefits for later cognitive development.

While this was a small study, it was randomized and used a placebo control group. Further studies are needed, yet the findings suggest that continuing folic acid beyond the first trimester may have beneficial neurodevelopmental effects for the child.

Clinical Implications

We have strong evidence for starting folic acid before conception and continuing it through early pregnancy. We do not yet have sufficient evidence to determine whether additional folic acid supplementation specifically improves neurodevelopment when continued throughout pregnancy; however, there is preliminary evidence that there may be some benefits of continuing folic acid throughout the pregnancy.

At the same time, there is no recommendation to stop folic acid after the first trimester, and recommended doses of folic acid have a strong safety record.

For women who are taking a prenatal vitamin during pregnancy, there is currently no reason to discontinue it solely because the period of maximal NTD prevention has passed. The emerging data on folic acid and neurodevelopment give us an additional reason to be interested in continued folate exposure throughout pregnancy, although these findings are not yet sufficient to establish a new clinical recommendation.

—Ruta Nonacs, MD PhD