Skipping folic acid during pregnancy raises the risk of serious birth defects, particularly problems with the brain and spinal cord known as neural tube defects. The most critical window is the first 28 days after conception, when the neural tube forms and closes. Because this happens before many people even know they’re pregnant, the consequences of low folate levels can already be set in motion by the time a positive test appears.
Neural Tube Defects: The Primary Risk
The neural tube is the structure in an embryo that becomes the brain and spinal cord. It forms and seals shut within roughly the first four weeks of pregnancy. If folate levels are too low during this window, the tube may not close completely, leading to one of two major birth defects.
Spina bifida occurs when the neural tube fails to close along the spine. The backbone doesn’t fully form around the spinal cord, often causing nerve damage that can affect movement, bladder and bowel control, and sensation in the legs. About 1,300 babies are born with spina bifida each year in the United States. Anencephaly, the more severe form, happens when the upper portion of the neural tube stays open. Babies with anencephaly are missing major parts of the brain, including the regions responsible for thinking and coordination. About 700 babies in the U.S. are affected annually, and the condition is fatal.
Folic acid supplementation prevents the majority of these cases. In a landmark clinical trial, daily supplementation starting before conception and continuing through the first trimester reduced neural tube defect recurrence by 71%. A separate Hungarian trial found that folic acid prevented roughly 90% of neural tube defects overall. These are not small, marginal effects. They represent one of the clearest prevention stories in all of prenatal medicine.
Heart Defects and Other Structural Problems
Neural tube defects get the most attention, but low folate levels are also linked to congenital heart defects and orofacial clefts like cleft lip and cleft palate. The same Hungarian intervention trials that showed a 90% reduction in neural tube defects found that folic acid supplementation also prevented about 40% of congenital heart defects. The connection makes biological sense: folate is essential for DNA replication in rapidly dividing cells, and the heart, face, and spine all form during the same early weeks of pregnancy when cell division is at its most intense.
Preterm Birth and Low Birth Weight
The risks don’t end with structural birth defects. A large meta-analysis published in Frontiers in Neuroscience found that women with higher blood folate levels had a 28% lower risk of preterm birth compared to those with the lowest levels. Folic acid supplementation specifically was tied to a 10% reduction in preterm delivery. Starting supplements before conception rather than after offered a slightly stronger protective effect.
Higher dietary folate intake from food alone was associated with a 32% lower risk of preterm birth, though the evidence was stronger for supplementation. The protective effect appeared most clearly at standard doses (under 1,000 micrograms per day). Higher “megadoses” did not show additional benefit for preventing preterm delivery.
Anemia in the Mother
Folate deficiency doesn’t only affect the baby. Without enough folic acid, your body can’t produce red blood cells normally. The result is a condition called megaloblastic anemia, where red blood cells grow too large, become oval instead of round, and don’t function as well. You end up with fewer red blood cells that also die off faster than normal.
Symptoms include persistent fatigue, pale skin, irritability, decreased appetite, diarrhea, and a smooth, tender tongue. During pregnancy, when your blood volume expands significantly to support the growing baby, anemia puts extra strain on your body and can compound the risks of preterm delivery.
Why Timing Matters So Much
The hardest part about folic acid and pregnancy is that the damage from deficiency happens before most people realize they’re pregnant. The neural tube closes by around day 28 after conception. That’s roughly two weeks after a missed period, and many people don’t test until around that time or later. By then, the window for preventing neural tube defects is already closing or closed.
This is why health organizations recommend that all people who could become pregnant take 400 micrograms of folic acid daily, even if they aren’t actively planning a pregnancy. About half of pregnancies are unplanned, so waiting until you know you’re pregnant to start supplementing is a gamble with the odds stacked against you.
Food Folate vs. Supplements
Folate occurs naturally in leafy greens, legumes, citrus fruits, and liver. Many grain products in the U.S. are also fortified with synthetic folic acid. However, natural food folate is only about 80% as bioavailable as the synthetic form in supplements. That means your body absorbs and uses a smaller fraction of the folate you get from food compared to a pill.
A folate-rich diet is valuable, but it’s difficult to consistently hit the levels needed to protect against neural tube defects through food alone, especially during the critical early weeks. This is why supplementation is recommended on top of a healthy diet rather than as a substitute for one.
Who Needs a Higher Dose
The standard recommendation of 400 micrograms daily is enough for most people, but certain groups face a higher baseline risk of neural tube defects and benefit from a much larger dose, typically 4 to 5 milligrams per day. You fall into this higher-risk category if you have:
- A previous pregnancy affected by a neural tube defect. The recurrence risk is about 4%, which is 40 times higher than the general population’s risk.
- Diabetes.
- Obesity with a BMI over 35.
- A malabsorption disorder such as inflammatory bowel disease, which can prevent your gut from absorbing folate efficiently.
- Use of certain medications that interfere with folate metabolism, including some anti-seizure drugs and methotrexate.
- Genetic variants affecting how your body processes folate.
- Smoking.
In the original trial studying women with prior neural tube defect pregnancies, 4 milligrams daily reduced recurrence by 75%. For women taking anti-seizure drugs or other folate-blocking medications near the time of conception, 5 milligrams daily through the end of the first trimester is typically recommended. These higher doses require a prescription, since over-the-counter prenatal vitamins contain the standard 400 to 800 microgram amount.
What Folic Acid Actually Does in the Embryo
Folate belongs to the B-vitamin family and plays a central role in DNA synthesis. Every time a cell divides, it needs to copy its entire set of DNA, and folate provides the chemical building blocks (called one-carbon groups) that make this possible. In the first weeks of pregnancy, cells are dividing at an extraordinary rate to form the brain, spinal cord, heart, and other organs. Without enough folate, this process slows down or goes wrong.
Recent research has revealed that folate’s role goes beyond just fueling cell division. The folate receptor on neural plate cells appears to be directly involved in the physical mechanics of neural tube closure. As the flat sheet of neural tissue folds into a tube, individual cells need to change shape, narrowing at the top and widening at the bottom. The folate receptor helps manage this process by facilitating the removal and redistribution of adhesion proteins on the cell surface. Without adequate folate signaling, cells can’t constrict properly, and the tube doesn’t fold shut. This helps explain why folate deficiency specifically disrupts neural tube formation rather than causing more generalized developmental problems.