Folic acid supplementation improves seizure, pregnancy outcomes in women with epilepsy

For Chinese women with epilepsy, periconceptional folic acid intake helps minimize the incidence of seizures during pregnancy and reduce the risk of pregnancy loss, as shown in a study.

In a cohort of pregnant women with epilepsy enrolled in the West China Pregnancy Registry of Epilepsy, the incidence of seizures in general (convulsive and nonconvulsive) was initially higher among folic acid users than nonusers during the first trimester (53.7 percent vs 45.4 percent; p=0.004). However, the numbers shifted over time and seizures became significantly less common among folic acid users vs nonusers in the third trimester (50.1 percent vs 63.9 percent, p=0.016). [Epilepsia 2026;doi:10.1002/epi.70093]

The incidence of convulsive seizures, specifically, was significantly lower among folic acid users than nonusers in the second (27.5 percent vs 43.2 percent; p=0.004) and third trimesters (21.5 percent vs 47.2 percent; p<0.001).

Among folic acid users, convulsive seizure recurrence was more common among those on low vs medium-to-high doses (second trimester: 29.6 percent vs 24.2 percent, p=0.026; third trimester: 23.8 percent vs 17.9 percent, p=0.011), those who initiated supplementation after vs before conception (first trimester: 31 percent vs 18 percent, p<0.001; second trimester: 32 percent vs 21 percent, p<0.001), and those who used folic acid for <3 vs ≥3 months (first trimester: p<0.001; second trimester: p=0.035).

“The protective effect of folic acid supplementation on seizures appears to increase over time, possibly as the body gradually builds folate concentrations to adequate levels. That approximately 60 percent of FA users in our registry started folic acid supplements after conception may also have partially contributed to this delayed response,” the investigators said.

They also emphasized that higher doses of folic acid supplements may “lead to faster buildup and restoration of folic acid concentration, and thus to earlier beneficial effects.”

Pregnancy outcomes

More than three-fourths of pregnancies (78.8 percent) among folic acid nonusers were lost as opposed to only 13.1 percent among folic acid users (relative risk [RR], 6, 95 percent confidence interval [CI], 5.18–7; p<0.001).

Compared with folic acid users, nonusers had a more than threefold increased risk of spontaneous abortion (16.8 percent vs 4.8 percent; RR, 3.5, 95 percent CI, 2.47–4.86; p<0.001) and sevenfold increased risk of elective pregnancy termination (62 percent vs 8.2 percent; RR, 7.5, 95 percent CI, 6.16–9.18; p<0.001).

The protective effect of folic acid use on the risk of pregnancy loss was more pronounced among women exposed to antiseizure medications (ASMs). The risk of pregnancy loss associated with folic acid use vs nonuse was more than sixfold lower for women exposed to ASMs (12.9 percent vs 83.5 percent; RR, 6.5, 95 percent CI, 5.48–7.60; p<0.001) and was fourfold lower for those who were not exposed to ASMs (13.8 percent vs 54.4 percent; RR, 4, 95 percent CI, 2.65–5.91; p<0.001).

Low folic acid dose, delayed initiation, and short use duration were associated with an increased risk of pregnancy loss.

“Mothers’ concerns about passing epilepsy to their children and the heightened congenital malformation risk of ASMs—particularly with potentially teratogenic ASMs—were among the most common triggers of elective abortion,” the investigators noted.

The finding on folic acid supplementation’s effect on pregnancy loss being more pronounced among women exposed to ASMs suggests that “folic acid may mitigate the additional baseline adverse effects of ASM exposure, beyond the pre-existing epilepsy-related risks,” they explained.

With regard to the effect of folic acid supplementation on major congenital malformations in the offspring of women with epilepsy, the most recent American Epilepsy Society guidelines concluded that the evidence remains uncertain. In line with this, the congenital malformation rate in the study cohort was not significantly different between folic acid users and nonusers. [Neurology 2024;102:e209279]

“The increased risk of congenital malformations in the offspring of people with epilepsy may occur through mechanisms independent of folic acid metabolism,” the investigators said.

They recommended individualized folic acid supplementation in women of childbearing age with epilepsy to ensure adequate folate levels. “This is essential for foetal development and affects the mother’s well-being and the risk of developing diseases later in life.” [Brain 2025;148:3801-3816]

The analysis included 1,638 pregnancies in 1,405 women with epilepsy. A total of 1,299 (79.3 percent) pregnancies were in 1,173 women who used folic acid supplements during periconception, and 1,351 (82.5 percent) were exposed to ASMs.