For women living with epilepsy, planning a pregnancy can come with questions that seem longer than the usual prenatal checklist. There’s the excitement of a baby’s imagination, but also the concern of staying healthy, preventing seizures, and making sure drug choices are as safe as possible.
A large new Nordic study offers a clear and practical solution: for women taking anticonvulsant drugs, starting high-dose folic acid before pregnancy may be more important than starting after a positive pregnancy test.
The study, published in Journal of Neurology, Neurosurgery & Psychiatryfound that women taking anticonvulsant drugs had about a 45% lower relative risk of major birth defects in their children when they started high-dose folic acid one to 12 weeks before pregnancy. Starting high-dose folic acid after the onset of pregnancy was not associated with the same protective effect.
Time is definitely of the essence. For women taking anticonvulsant medications, folic acid may be most helpful when it is already in the body before the first weeks of fetal development begin.
This matters because many people don’t know they are pregnant until a few weeks later. By then, some of the baby’s first developmental steps have already begun.
Women with epilepsy are often in a difficult position when considering pregnancy. Anticonvulsant medications may be necessary to prevent seizures, and stopping or changing them without medical guidance can be dangerous. At the same time, some anticonvulsant drugs are associated with a higher risk of major congenital anomalies, which are large structural differences present at birth or diagnosed early in life.
Because of this, many women taking anticonvulsant medications are advised to take higher doses of folic acid before and during pregnancy. But until now, the evidence about how much it helps, and when it helps the most, has been mixed.
This study helps clarify an important part of the picture: onset before pregnancy appears to be the key window.
The researchers analyzed national health data from Denmark, Iceland, Norway and Sweden. They looked at pregnancies among women taking anticonvulsant drugs and compared those who filled prescriptions for high-dose folic acid at different points in pregnancy with those who did not.
The strongest benefit was seen in women who started high-dose folic acid one to 12 weeks before pregnancy. In this group, the rate of major congenital anomalies was 2.6%, compared with 4.8% among women who did not start high-dose folic acid during this window. This equates to an absolute risk reduction of approximately 2.2 percentage points and a relative risk reduction of 45%.
Folic acid is a synthetic form of folate, a B vitamin that helps the body produce healthy new cells. It is especially important in early pregnancy, when the baby’s brain, spine and organs begin to form.
In the general population, folic acid is best known for reducing the risk of neural tube defects, which affect the development of the brain and spinal cord. For women taking anticonvulsant drugs, doctors often recommend higher doses because some drugs can interfere with folic acid pathways or are associated with higher risks during pregnancy.
The key issue is that early growth happens quickly.
By the time someone misses a period, takes a pregnancy test, makes an appointment, and starts a supplement, they may already be five, six, or seven weeks pregnant based on standard pregnancy appointments. The study found that many women started taking high-dose folic acid around weeks six and seven, likely when they realized they were pregnant. However, onset within the first 12 weeks after the onset of pregnancy was not associated with a lower risk of major birth defects.
This does not mean that folic acid is useless once pregnancy begins. It means that, for this particular group and for this particular outcome, waiting until pregnancy is confirmed may be too late to reap the greatest potential benefit.
The SCAN-AED study included women aged 18 to 49 who had recorded pregnancies and were using anticonvulsant medications. The researchers used national register data from four Nordic countries, covering births in different years between 1997 and 2020.
They compared initiation of high-dose folic acid during three key windows:
- 13 to 52 weeks before pregnancy
- one to 12 weeks before pregnancy
- one to 12 weeks after the onset of pregnancy
High-dose folic acid in the study generally meant 4 or 5 mg per day, depending on the country. This is higher than what is found in many standard prenatal vitamins.
The outcome the researchers focused on was major congenital anomalies diagnosed before the age of one year. These are important structural conditions, not minor differences.
This was not a randomized clinical trial. Instead, the researchers used a method called target trial simulation, which uses real-world health data, trying to mimic the structure of a clinical trial as closely as possible. This is important because randomized trials in pregnancy can be difficult or unethical in some cases.
Like all observational studies, it cannot prove cause and effect with absolute certainty. But its large size and time-focused design make the findings significant.
One of the most important findings is what the study did not find.
Women who started high-dose folic acid in the first 12 weeks after the start of pregnancy did not have a reduced risk of major birth defects compared with women who did not start. In fact, the study reported a rate of major congenital anomaly of 5.7% among those who started after the onset of pregnancy, compared to 4.5% among non-starters, although the researchers noted that this may be influenced by other factors, such as women at higher risk being more likely to start supplementation after pregnancy was recognized.
The takeaway is not that starting after pregnancy is harmful. The bottom line is that starting after pregnancy was not associated with the protective effect seen when women started before pregnancy.
This is a very human problem. Many pregnancies are unplanned. Many people do not receive preconception counseling. Some women may not know that their medications change their folic acid recommendations. Others may assume that a regular prenatal vitamin is enough.
That’s why this study points to the need for earlier conversations, not blame.
The study also looked at women taking specific anticonvulsant medications. Among women taking drugs with higher known teratogenicity, including valproate, topiramate, carbamazepine, phenobarbital, or phenytoin, starting high-dose folic acid one to 12 weeks before pregnancy was associated with an even greater risk reduction.
The researchers also saw a lower risk among women taking lamotrigine when they started high-dose folic acid before pregnancy.
These findings do not mean that one should stop, change, or adjust anticonvulsant medication on their own. Decisions about taking medications during pregnancy are highly individualized and should be made with a neurologist, obstetrician, or maternal-fetal medicine specialist.
For women taking anticonvulsant medications, this study supports a proactive approach to pregnancy planning.
This may include talking to a health care provider about whether high-dose folic acid is recommended, what dose is appropriate, when to start, whether current medication is the safest option for pregnancy, and what to do if pregnancy occurs unexpectedly.
It is important to note that high dose folic acid is not the same as a standard prenatal vitamin. Many prenatal vitamins contain a much smaller amount. Because high-dose folic acid may not be suitable for everyone, it should be taken under medical guidance.
For women who are already pregnant, this study should not cause panic. There is no reason to stop taking anticonvulsants, and there is no reason to feel guilty if folic acid was started later. Many people do not receive this information until after the pregnancy begins.
The best next step is to talk to a health care provider as soon as possible about medication, folic acid, prenatal screening, and ongoing care.
This study also highlights a gap in women’s health care: pregnancy planning advice often arrives too late.
A neurologist may focus on seizure control. An obstetrician may not become involved until the pregnancy is already underway. A family doctor may not know that someone is planning to conceive. And the patient may not realize she needs a different folic acid regimen until she is already pregnant.
For women taking anticonvulsant medications, these conversations need to happen sooner.
Preconception care should not be treated as a bonus or an afterthought. It is part of safe, informed reproductive health care. Women deserve clear instructions before pregnancy, especially when taking medications that may affect fetal development.
