This population-based study assessed whether pregnant women taking topiramate during the first trimester had a higher risk of giving birth to infants with oral clefts.

Study design

The cohort included 1,360,101 pregnant women enrolled in Medicaid from 3 months before conception through 1 month after delivery. Only mothers with live-born infants were included.

Outcomes

The analysis showed that the risk of oral clefts at birth was 4.1 per 1,000 for women exposed to topiramate compared with 1.1 per 1,000 in the unexposed group.

The median daily dose for the first prescription filled during the first trimester was 200 mg for women with epilepsy and 100 mg for women without epilepsy. The risk was higher for infants whose mothers took the higher dose.

Limitations

This cohort was restricted to live births. Therefore, severe congenital malformations that result in pregnancy losses or terminations would have been missed.

Clinical significance

The findings here show that use of topiramate early in pregnancy could potentially harm the fetus. This study is important because topiramate is commonly used by neuro-ophthalmologists to treat migraine and pseudotumor cerebri.