For women taking antiseizure medications, when folic acid supplementation begins may make a meaningful difference in pregnancy outcomes. A large new study published in Journal of Neurology, Neurosurgery & Psychiatry found that starting high-dose folic acid before pregnancy was associated with a substantially lower risk of major birth defects, while starting after pregnancy began showed no measurable benefit.
Researchers analyzed data from more than 13,000 pregnancies across Denmark, Norway, Sweden and Iceland, focusing on women using antiseizure medications, which are known to increase the risk of congenital anomalies. They found that the rate of major birth defects was about 48 per 1,000 pregnancies among women who did not take high-dose folic acid, compared with about 26 per 1,000 among those who began supplementation one to 12 weeks before pregnancy. That translates to an absolute reduction of 22 cases per 1,000 pregnancies, or about a 45% lower risk.
“We observe a clear association between the timing of initiation of high dose folic acid supplementation and the risk of congenital anomalies,” said Jakob Christensen, a neurologist and professor at Aarhus University.
The study also found no reduction in risk when folic acid supplementation was started after pregnancy began, highlighting what researchers describe as a critical window before conception. In subgroup analyses, the association appeared even stronger among women taking medications linked to higher risk, including valproate.
Folic acid has long been recommended during pregnancy to help prevent neural tube defects, but evidence on higher-dose supplementation for women taking antiseizure medications has been limited and sometimes inconsistent. By accounting for the timing of supplementation, the researchers say this study helps clarify that gap.
“This work shows that timing is a crucial factor,” said Yuelian Sun, the study’s first author.
The findings should be interpreted with some caution. This was an observational study using registry data, meaning it cannot prove cause and effect, and there may be other factors that influenced outcomes. The results also apply specifically to women taking antiseizure medications and do not suggest that all women need high-dose folic acid.
Still, the study offers a clear practical insight for a high-risk group. Because early fetal development occurs before many women know they are pregnant, the timing of nutrient intake can be critical. For women taking antiseizure medications, planning ahead and discussing both medication use and supplementation with a healthcare provider may be an important step in reducing risk.
This study was supported by NordForsk, the Trond Mohn Foundation and the Research Council of Norway.