Essential Reads: Why All Women of Reproductive Age Should Take Folic Acid

In 2025, Folic Acid Awareness Week will be observed from September 7th to September 14th. This week is dedicated to raising awareness about the importance of folic acid, particularly for women of reproductive age, in preventing neural tube defects in babies. Folate or vitamin B-9 is an essential nutrient. Folate is needed for DNA replication and repair and proper cell growth; thus is essential for fetal development. There are many dietary sources of folate, including dark green leafy vegetables, beans, peas, nuts, and liver. Fruits rich in folate include oranges, lemons, bananas, melons and strawberries. Nonetheless, many women have diets which do not provide sufficient levels of folate. It turns out that it is very difficult for most women to get the recommended daily amount of folate from diet alone. Folate Fact Sheet for Health Professionals (NIH) Over-the-counter multivitamins contain folic acid, which is the synthetic form of folate. The recommended daily amount of folate for adults is 400 mcg. For pregnant women, the recommended amount is 600 mcg. Synthetic folic acid has greater bioavailability than naturally occurring folate found in food. (At least 85% of folic acid is bioavailable, whereas only about 50% of folate naturally present in food is bioavailable.) Folate Deficiency and Risk of Neural Tube Defects and Other Birth Defects Inadequate folate intake during pregnancy has been associated with increased risk of neural tube defects, including spina bifida and anencephaly. It is estimated that about 70% of all neural tube defects could be prevented with folic acid supplementation. Low maternal folate levels and insufficient folic acid supplementation during the periconceptional period have been linked not only to neural tube defects but a broader range of other congenital abnormalities, including certain congenital heart and urinary tract defects, oral facial clefts, and limb-reduction anomalies. Research indicates that adequate folate status and regular use of folic acid before and during early pregnancy are associated with a reduced risk of congenital heart defects and oral clefts in newborns. Folate Deficiency and Risk of Autism Current research suggests that autism spectrum disorders (ASD) occur as a result of events that take place during pregnancy. While genetic factors play an important role, non-heritable risk factors contribute to a substantial proportion of ASD cases. Maternal nutrition has been a focus of interest as a factor which may influence risk for ASD. In two studies — one an American case-control study, CHARGE (CHildhood Autism Risks from Genetics and Environment) and, the other, a Norwegian cohort study (Norwegian Mother and Child Cohort Study (MoBa)) — maternal folic acid intake during the periconceptual period and early pregnancy was associated with a significant reduction in risk of ASD. In a Swedish study from 2017, maternal multivitamin use was associated with a lower odds of having a child with ASD with intellectual disability compared to mothers who did not use multivitamins, iron, or folic acid (odds ratio 0.69, 95% confidence interval 0.57 to 0.84). Many, but not all, studies indicate that maternal multivitamin or folic acid supplementation during the periconceptual period may be associated with a decreased risk of ASD. While there may be factors other than folic acid that explain these findings, the risks associated with multivitamin use, specifically folic acid, are low, and the potential benefits of multivitamin use are high. Current Recommendations for Folic Acid Supplementation Since 1998, the Food and Drug Administration (FDA) has required the addition of folic acid to many enriched breads and cereals in order to increase the amount of folic acid in our diets. Since this FDA recommendation was put into place, there has been about a 65% reduction in the prevalence of neural tube defects in the general population. However, national data indicate that, even in regions with folic acid food fortification, a substantial proportion of women, particularly those of reproductive age, do not meet daily folate requirements through diet alone. All major organizations (CDC, ACOG, USPSTF) recommend that all persons who could become pregnant take a daily supplement containing 400–800 mcg of folic acid. The benefit is substantial and consistently documented, and these standards have been reaffirmed recently (USPSTF 2023, CDC 2025). Most multivitamins contain 400 micrograms or 0.4 milligrams of folic acid. Most prenatal vitamins have approximately 800 micrograms or 0.8 milligrams of folic acid. Folic Acid Should Be Taken At Least One Month Before Conception Because 50% of all pregnancies are unplanned, any woman who could potentially become pregnant should take folic acid daily, even if they are not planning pregnancy. This is important because folic acid is needed in the first weeks of pregnancy, even before a woman may be aware that she is pregnant. In addition, using folic acid for at least one month before conception has been associated with decreased risk for autism spectrum disorders. In contrast, starting folic acid after conception may not provide the same benefit. Who is At Higher Risk for Folate Deficiency? Some women are more likely to require higher than standard doses of folic acid or supplementation with folate-related compounds, such as l-methylfolate. Specific guidelines can be found in this article. Previous Child with Neural Tube Defect: It is recommended that women who have had a baby with a neural tube defect should take 4,000 mcg (4mg) of folic acid daily starting at least one month before conception and continuing through the first trimester. Women with MTHFR C677T Gene Variants: Some individuals carry genetic variants of the methylenetetrahydrofolate reductase (MTHFR) enzyme. This enzyme is crucial for converting folate to its active form, and those carrying certain variants, specifically the MTHFR C677T gene polymorphism, may be more vulnerable to folate deficiency. Folic acid (at 400-800 mcg daily) remains the recommended form for neural tube defect prevention, even in women who carry MTHFR C677T variants. Research demonstrates that standard supplementation (400–800mcg daily) effectively reduces neural tube defect risk in this population. Most individuals with the C677T variant are able to convert folic acid to its active form, albeit less efficiently. In addition, there are other women who are at greater risk for folate deficiency during pregnancy. Risk factors for folate deficiency include: Insulin-dependent diabetes Obesity Smoking Use of certain antiepileptic drugs (e.g., valproic acid, carbamazepine) Use of folate antagonists (e.g., methotrexate, sulfonamides) High-risk ethnic groups (e.g., Sikh, Celtic, Northern Chinese) However, guidelines regarding the appropriate dose of folic acid for these groups are not well-established. The Bottom Line The CDC, the U.S. Public Health Service and the American College of Obstetricians and Gynecologists (ACOG) urge every woman who could become pregnant to take at least 400 micrograms (400 mcg) or 0.4 milligrams of folic acid every day. Most multivitamins contain 400 micrograms or 0.4 milligrams of folic acid. Most prenatal vitamins have approximately 800 micrograms or 0.8 milligrams of folic acid. Also relevant is the finding that women with untreated psychiatric illness are less likely to take prenatal vitamins. Thus, when prescribing medications to any woman of reproductive age, this is a good opportunity to provide information on the importance of folic acid for fetal development and to encourage the use of folic supplements in either multivitamins or prenatal vitamins. Ruta Nonacs, MD PhD References: Centers for Disease Control and Prevention (CDC). (2025). MTHFR gene variant and folic acid facts. DeVilbiss EA, Magnusson C, Gardner RM, Rai D, Newschaffer CJ, Lyall K, Dalman C, Lee BK (2017). Antenatal nutritional supplementation and autism spectrum disorders in the Stockholm youth cohort: Population based cohort study. BMJ, 359, j4273. Liu X, Zou M, Sun C, Wu L, Chen WX (2021). Prenatal folic acid supplements and offspring’s autism spectrum disorder: A meta-analysis and meta-regression. Journal of Autism and Developmental Disorders, 51(3), 981–998. Surén P, Roth C, Bresnahan M, Haugen M, Hornig M, Hirtz D, Lie KK, Lipkin WI, Magnus P, Reichborn-Kjennerud T, Schjølberg S, Davey Smith G, Øyen AS, Susser E, Stoltenberg C (2013). Association between maternal use of folic acid supplements and risk of autism spectrum disorders in children. JAMA, 309(6), 570–577. Schmidt RJ, Tancredi DJ, Ozonoff S, Hansen RL, Hartiala J, Allayee H, Schmidt LC, Tassone F, Hertz-Picciotto I (2012). Maternal periconceptional folic acid intake and risk of autism spectrum disorders and developmental delay in the CHARGE case-control study. American Journal of Clinical Nutrition, 96(1), 80–89. Wang D, Jin L, Zhang J, Meng W, Ren A, Jin L. Maternal periconceptional folic acid supplementation and risk for fetal congenital heart defects. J Pediatr. 2022 Jan;240:72-78.