Impact of folic acid supplementation on seizures, maternal and fetal outcomes in pregnant Chinese women with epilepsy

OBJECTIVE: This study was undertaken to assess whether periconceptional folic acid (FA) supplementation affects seizures, maternal, and fetal outcomes in Chinese women with epilepsy. METHODS: We included pregnant women with epilepsy enrolled in the West China Pregnancy Registry of Epilepsy between 2012 and 2021. Detailed data on maternal health, FA intake, antiseizure medications (ASMs), pregnancy, and perinatal outcomes were obtained during regular visits to neurology clinics. Primary outcomes were seizure control status and adverse maternal and fetal outcomes. To adjust for potential confounders, subgroup and sensitivity analyses were performed. RESULTS: We included 1638 pregnancies of 1405 women with epilepsy. A total of 1299 (79.3%) pregnancies in 1173 women used FA supplements during periconception, and 1351 (82.5%) pregnancies were exposed to ASMs. The recurrence rate of convulsive seizures was significantly higher among non-FA users compared with FA users throughout pregnancy. Low FA dose, delayed initiation, and short use duration were associated with an increased risk of seizures during pregnancy. Most pregnancies (78.8%) in the non-FA group were lost compared to 13% in the FA group (p < .001). Non-FA users had 3.5-fold and 7.5-fold increased risks of spontaneous and elective abortions compared with FA users. The protective effect was more prevalent among those using ASMs. Pregnancies exposed to low-dose FA had higher rates of adverse maternal-fetal outcomes than those receiving medium- to high-dose FA supplements. SIGNIFICANCE: Periconceptional FA intake by women with epilepsy was associated with an approximately 66% decreased risk of abortion and improved seizure control during pregnancy. Low-dose FA may be insufficient to prevent adverse maternal-fetal outcomes in this population. Further studies are warranted to confirm these findings.