Folic acid alone is unlikely to eliminate neural tube defects, according to Gram Research analysis of a 2026 review of 74 studies. Folic acid reduced open neural tube defects by nearly 30%, but closed defects have not declined, suggesting genetics, certain medicines, and metabolic and dietary factors also matter.
Neural tube defects are serious birth conditions that affect the brain and spine, and roughly 214,000 to 322,000 babies are born with one each year worldwide. Folic acid, a B vitamin, cut the open forms by nearly 30%, but closed forms have not declined. According to research reviewed by Gram, a 2026 review of 74 studies suggests that genes, medicines taken during pregnancy, environmental exposures, and metabolic and dietary factors may all play a role. The authors conclude that folic acid alone is unlikely to eliminate these conditions. They call for more research and prevention efforts that go beyond the vitamin.
Key Statistics
A 2026 review of 74 peer-reviewed studies published in the American Journal of Obstetrics and Gynecology MFM found that folic acid reduced open neural tube defects by nearly 30%, while closed neural tube defects showed no comparable decline.
According to research reviewed by Gram, an estimated 214,000 to 322,000 infants are born with a neural tube defect each year worldwide, according to a 2026 review of 74 studies.
The Quick Take
- What they studied: Researchers wanted to know what causes neural tube defects besides a lack of folic acid, and which factors other than this vitamin may raise a baby’s risk.
- Who participated: No new people were enrolled. The authors reviewed 74 peer-reviewed studies written in English, so the findings describe what earlier research has already measured in many different populations.
- Key finding: Folic acid lowered open neural tube defects by nearly 30% after the vitamin was introduced in the early 1990s, but closed neural tube defects did not decline. This gap suggests that other factors also contribute to these conditions.
- What it means for you: Taking folic acid before and during early pregnancy is still an important step. It is not a complete answer, though. Other factors, including genes, some medicines, and overall health, may also affect risk, so talk with a healthcare provider about your own situation.
The Research Details
This study is a review, which means the authors did not run a new experiment. Instead, they gathered and read earlier research on neural tube defects. They included 74 peer-reviewed studies published in English. Each study was checked for information about factors that may raise risk beyond folic acid.
The authors sorted the findings into two main groups. The first group covers genetic pathways, which are inherited or gene-related influences. The second group covers environmental exposures. Within that group, the authors separated general exposures from exposures caused by medical treatments, which they call iatrogenic exposures, and from metabolic and dietary factors, which relate to how the body processes food and energy.
By organizing the evidence this way, the review lets readers see the range of possible causes in one place. It does not test any single cause directly, so it shows where the evidence points rather than proving cause and effect.
A review like this is useful because neural tube defects have many possible causes that are spread across several studies. Reading them together helps show which factors have been studied most, where the evidence is strong, and where big gaps remain. This makes it easier for doctors, researchers, and public health leaders to plan the next steps.
The review was published in a respected journal focused on pregnancy and maternal-fetal medicine. Reviews are useful for seeing the big picture, but their strength depends on the quality of the studies they include. Because the authors included only English-language studies, some relevant research published in other languages may have been missed. The review also does not report a single combined number, so readers should treat its conclusions as a summary of the evidence rather than a precise measurement.
What the Results Show
The clearest result comes from the long-running history of folic acid. When folic acid was added to foods and recommended to women in the early 1990s, the rate of open neural tube defects fell by nearly 30%. Open defects are those where part of the spinal cord or brain is exposed. This is a major success for public health.
Closed neural tube defects did not show the same decline. Closed defects are covered by skin and tissue, and they include conditions such as spina bifida occulta. Their rates have stayed about the same, which tells researchers that folic acid works on some pathways but not others.
The review also points to other factors that may be involved. Genetic differences may affect how a baby’s neural tube forms. Certain medicines taken during pregnancy may raise risk, and some metabolic and dietary conditions may also play a role. The authors describe these as possible contributors that need further study, not as settled causes.
The review stresses that neural tube defects are biologically varied. In plain terms, they are not one single disease with one single cause. This matters because a single solution, such as one vitamin, is unlikely to prevent all of them. The authors note that folic acid supplementation and fortification alone are unlikely to remove the global burden of these conditions.
The authors also call for multidisciplinary strategies, which means teamwork among doctors, genetic counselors, nutrition experts, and public health officials. This approach could help identify high-risk pregnancies earlier and tailor prevention to each family.
The folic acid story is well established. Public health campaigns in many countries have credited folic acid with large drops in open neural tube defects since the early 1990s. This review builds on that success by showing that the same approach has not helped closed defects. It fits with a growing view in birth defect research that multiple causes, not one nutrient, shape these conditions.
The review does not calculate a combined effect size for each risk factor, so it cannot say how much each one raises risk. Many of the included studies may be observational, meaning they track people over time rather than assigning treatments, which makes it hard to prove that a factor directly causes a defect. Only English-language studies were included, which may leave out useful research from other countries. The review also reflects the current state of knowledge, which may change as new studies appear.
The Bottom Line
Research shows that folic acid remains one of the most effective known ways to lower the risk of open neural tube defects, so taking it before and during early pregnancy is still recommended (high confidence). Evidence that genetics, certain medicines, and metabolic or dietary factors contribute is promising but less definitive (moderate confidence). Anyone planning a pregnancy should review their medicines and health conditions with a clinician.
People who are planning a pregnancy, are pregnant, or are working in maternal health, genetics, or public health should pay close attention. Readers who are not pregnant and not planning a pregnancy may find the information interesting, but it does not require any personal change. Anyone with a family history of neural tube defects should speak with a genetic counselor or doctor.
Folic acid needs to be in the body before a pregnancy begins, because the neural tube forms very early, often before a person knows they are pregnant. Changes in medicine use or diet can be made before conception. Changes in research practice and public health policy usually take years to show up in birth rates.
Frequently Asked Questions
Does folic acid prevent all neural tube defects?
Folic acid does not prevent all neural tube defects. A 2026 review of 74 studies found it reduced open defects by nearly 30% after its introduction in the early 1990s, but closed defects did not decline. Other factors, including genetics and some medicines, appear to play a role.
How many babies are born with neural tube defects each year?
An estimated 214,000 to 322,000 infants are born each year worldwide with a neural tube defect. These conditions range in severity and affect the brain or spine. A 2026 review of 74 studies notes that many forms remain less understood than open defects.
What causes neural tube defects besides low folate?
A 2026 review of 74 studies suggests that genetic pathways, certain medicines taken during pregnancy, environmental exposures, and metabolic and dietary factors may all contribute. Researchers describe these as possible contributors that need further study rather than confirmed causes.
When should I start taking folic acid if I want to get pregnant?
Folic acid should ideally be taken before conception, because the neural tube forms very early in pregnancy, often before a person knows they are pregnant. Anyone planning a pregnancy should ask a healthcare provider about the right dose and timing for their situation.
Want to Apply This Research?
- Log daily folic acid intake from a prenatal vitamin or supplement, and set a reminder to take it at the same time each day. For users planning a pregnancy, add a note on medicines and any chronic health conditions so they can review them with a clinician.
- Encourage users to take a folic acid supplement as advised by their doctor before trying to conceive, and to pair it with a daily routine such as taking it with breakfast. Suggest a conversation with a healthcare provider about all current medicines before pregnancy.
- Track supplement consistency, pre-pregnancy checkup dates, and any medication reviews over several months. Add a simple quarterly check-in asking whether the user has discussed family history or new medicines with a provider. Users should be reminded that the app supports, rather than replaces, medical advice.
This article summarizes a review of previously published research and is for general education only. It is not medical advice. Neural tube defect risk depends on many individual factors. Anyone who is pregnant, planning a pregnancy, or taking medicine should talk with a qualified healthcare provider before making changes to supplements, medications, or diet.
This research translation is published by Gram Research, the science division of Gram, an AI-powered nutrition tracking app.