Neural Tube Defects and Folic Acid: What They Are and How to Lower the Risk

Neural tube defects (NTDs) are serious birth defects that occur when the embryo's neural tube fails to close correctly, and they include spina bifida, anencephaly, and encephalocele.¹ Taking 400 mcg of folic acid every day, starting before pregnancy, lowers the risk of many of them, and it is the best-established benefit folic acid has.²¹

This page explains what NTDs are, why timing is everything, how strong the folic acid evidence is, who is at higher risk, and what prevention looks like for average-risk and high-risk pregnancies.

What are neural tube defects?

NTDs result from failure of the embryonic neural tube to close correctly.¹ USPSTF names three main types:¹

• Spina bifida
• Anencephaly
• Encephalocele

USPSTF estimates that about 3,000 U.S. pregnancies are affected each year.¹ The outcomes can include infant death or lifelong disabilities affecting the nervous system, bones and joints, bowel, and bladder.¹

Why do NTDs happen so early?

The neural tube normally closes about 26 to 28 days after fertilization.³⁴ For many people, that is before they realize they are pregnant.³

This timing shapes the whole prevention strategy. Starting folic acid only after a positive pregnancy test may miss part or all of the window.³ That is why recommendations apply to everyone who could become pregnant, and why USPSTF advises starting at least one month before conception.²¹

How does folic acid help prevent NTDs?

Folate carries the building blocks cells need to make DNA and divide.⁵ That makes it especially important when cells divide rapidly, as they do during embryonic development.⁵ Low maternal folate increases NTD risk.⁵

How strong is the evidence?

Evidence grade: Established. Preventing NTDs is the strongest and most actionable use of folic acid. Randomized trials, observational studies, and fortification experience all support taking folic acid before conception and in early pregnancy.²¹ USPSTF judges the net benefit to be substantial, with high certainty, and gives the recommendation an A grade.¹

Only folic acid has the direct proof

CDC states that folic acid is the only form of folate demonstrated in studies to help prevent NTDs.⁶ Natural food folate and 5-MTHF (methylfolate) can contribute to folate nutrition, but they do not have equivalent direct NTD-prevention trial evidence.⁶²

What does fortification tell us?

Since 1998, the United States has required folic acid fortification of specified enriched cereal grain products at 140 mcg per 100 g, including many enriched breads, flours, cereals, rice, pasta, and cornmeal products.⁷⁵

The results at the population level have been substantial:

Fortification complements, but does not replace, the supplement recommendation for people who could become pregnant.⁸⁹ Learn which products are fortified in our guide to fortified foods with folic acid.

Who is at higher risk of an NTD?

Some factors raise NTD risk above average. According to ACOG and USPSTF, they include:¹⁰¹

• A previous pregnancy affected by an NTD
• A personal, partner, or family history of NTDs
• Certain antiseizure medicines
• Malabsorption after bariatric procedures
• Diabetes that was present before pregnancy
• Obesity

Low maternal folate also increases risk.⁵ People with these risk factors need preconception counseling rather than self-prescribing, because the right dose can differ by guideline and situation.¹⁰¹

How much folic acid prevents NTDs?

Prevention looks different for average-risk and high-risk pregnancies. Keep these two groups separate.

Average risk: 400 mcg

CDC recommends 400 mcg of folic acid daily for everyone capable of becoming pregnant, from supplements, fortified foods, or both, in addition to a varied diet.¹¹² For average-risk people, taking more than recommended is not known to provide better NTD prevention.¹²

High risk: 4 mg, with a clinician

CDC recommends 4,000 mcg (4 mg) daily for someone who has had a previous NTD-affected pregnancy and is planning another.⁶² This is well above the adult upper limit of 1,000 mcg a day for folic acid from supplements and fortified foods, so it should be coordinated with a clinician.⁶⁵

For more on dosing, see how much folic acid for pregnancy, and for timing, see folic acid before pregnancy.

Why diet alone is not enough

Natural folate is found in leafy vegetables, beans and peas, asparagus, Brussels sprouts, avocado, citrus, nuts, liver, eggs, and other foods.⁶⁵ Eating these foods supports good nutrition, but there are three reasons the guidelines still call for folic acid:

1. Absorption differs. About 50% of natural food folate is bioavailable, compared with at least 85% of folic acid taken with food.⁵
2. The need is high. Total folate need in pregnancy is 600 mcg DFE a day, which can be hard to get reliably from unfortified foods alone.⁵¹³
3. The proof is specific. Folic acid is the form shown in studies to help prevent NTDs.⁶

Also note that "whole grain" and "enriched" are not the same. Mandatory folic acid fortification generally applies to enriched grain products, so a whole-grain product is not necessarily fortified unless its label says so.¹⁴⁶

MTHFR and NTD prevention

Common MTHFR gene variants change how active one folate enzyme is, but they do not make a person unable to process folic acid.¹² People with the 677TT genotype have, on average, blood folate levels about 16% lower than people with the 677CC genotype at the same intake.¹² However, how much folic acid someone takes daily, and for how long before pregnancy, affect blood folate more than the common genotype does.¹²

CDC continues to recommend 400 mcg a day of folic acid for people with common MTHFR variants who could become pregnant.¹² Read more on folic acid and MTHFR.

Myths about NTDs and folic acid

Spreading these facts helps, too. Our page on folic acid awareness week has short, shareable messages you can use.

This article is for general education and is not medical advice. Doses and needs differ from person to person, so talk with your clinician or pharmacist about your situation. Read our editorial policy and medical disclaimer.