Periconceptional folic acid lessens risk of preterm birth in epileptic women on antiseizure drugs

Periconceptional folic acid when taken by epileptic women on anti-seizure medication lowered the risk of preterm birth as per a study that was published in the journal 'Neurology.' 

Epileptic women undergoing treatment with antiseizure medication (ASM) have an increased risk of pregnancy complications including preterm birth, fetal growth restriction, and preeclampsia. Hence, researchers conducted a study to investigate whether folic acid supplementation is associated with these pregnancy complications in women with epilepsy using ASM. They included Singleton pregnancies in the prospective Norwegian Mother and Child Cohort Study (MoBa) from 1999–2008. Using the MoBa questionnaires and the Norwegian Medical Birth Registry information on maternal epilepsy, ASM, folic acid supplementation, and pregnancy outcomes were obtained. Periconceptional folic acid supplementation was defined as intake between 4 weeks before pregnancy and 12 weeks into pregnancy and the information was retrospectively collected by the recall of the mothers in weeks 17–19. The primary outcomes were preterm birth (gestational age <37 weeks at birth), small for gestational age (SGA), and preeclampsia.  

Results: 

• The study included 1,00,105 pregnancies. Out of these 99,431 were without maternal epilepsy, 316 with maternal epilepsy and ASM exposure in pregnancy, and 358 with untreated maternal epilepsy.
• Among ASM-treated women with epilepsy, the risk of preterm birth was higher in those who did not use periconceptional folic acid (n = 64) compared with those who did (n = 245, the reference), while the risk of preterm birth among the reference was similar to the risk among women without epilepsy using folic acid periconceptionally.
• ASM-treated women with epilepsy starting folic acid after the first trimester had a higher risk compared with women without epilepsy with similar timing of folic acid, and even higher if not using folic acid.
• Folic acid was not associated with the risk of preterm birth among women with epilepsy without ASM or among women without epilepsy.
• Folic acid was not associated with the risk of preeclampsia or SGA among women with epilepsy.  

Thus, the researchers concluded that periconceptional folic acid was associated with a lower risk of preterm birth in epileptic women using ASM and this study supports the recommendation that ASM-treated women with epilepsy of childbearing potential should use folic acid supplementation regularly. 

TAKE-HOME MESSAGE

Women with epilepsy, particularly when exposed to antiseizure medications (ASMs), have a high risk of pregnancy complications. The supplementation of folate, an essential ingredient for DNA synthesis, is generally recommended during pregnancy, but more evidence is needed regarding the specific impact of folate supplementation on pregnancy. This study used data from a prospective pregnancy cohort study in Norway to assess the impact of folic acid supplementation on the risks of preterm birth, preeclampsia, or restricted fetal growth, in women receiving and not receiving treatment for epilepsy and ASMs. In the group of women with epilepsy using ASMs, among those using folic acid supplements periconceptionally, 5% of pregnancies resulted in preterm birth, and among those not taking folic acid, 14% of pregnancies resulted in preterm birth. The risk of preterm birth did not differ between women without epilepsy and ASM-treated women who used folic acid periconceptionally. Delaying supplementation until late in pregnancy was associated with a higher risk of preterm birth and the risk was highest in ASM-treated women who did not take folic acid.

These results provide important information regarding the impact of folic acid supplementation. The findings support a recommendation for ASM-treated women with epilepsy to use folic acid supplementation if they have the potential to become pregnant.

To read the full article, click here: https://doi.org/10.1212/WNL.0000000000200669 

Alvestad S, Husebye ESN, Christensen J, et al. Folic Acid and Risk of Preterm Birth, Preeclampsia, and Fetal Growth Restriction Among Women With Epilepsy. Neurology. 2022;99(6):e605-e615. doi:10.1212/wnl.0000000000200669