Topiramate (TPM, marketed as Topamax) is an antiepileptic drug which is also used for migraine prophylaxis, weight loss, and, less commonly, as a mood stabilizer.  Over the last few years we have seen several studies suggesting an increased risk of oral clefts in infants exposed to topiramate during the first trimester of pregnancy.  You can read more about those studies here:

More on Topiramate (Topamax) and Risk of Oral Clefts

Topiramate (Topamax) Associated with an Increased Risk of Oral Clefts

In order to further evaluate the association between topiramate and risk of oral clefts (OCs), a recent retrospective cohort study used automated data from four insurance claims databases.  The researchers compared the prevalence of OCs in three different groups of infants:

  • Infants of women exposed to TPM in the first trimester (TPM cohort)
  • Infants of women previously exposed to TPM or other antiepileptic drugs (formerly exposed [FE] cohort)
  • Infants of women with similar medical profiles (SMPs) to the TPM cohort that were not exposed to TPM (SMP cohort)

The prevalence of OCs was 0.36% (7/1945) in the TPM cohort, 0.14% (20/13512) in the FE cohort, and 0.07% (9/13614) in the SMP cohort.  Standardized by site, the prevalence ratio (PR) for TPM versus FE was 2.5 (95% CI: 1.0-6.0) and for TPM versus SMP was 5.4 (95% CI: 2.0-14.6). Adjustment for covariates one at a time or by propensity score yielded similar results.

Consistent with other research, it appears that first-trimester TPM exposure was associated with an increased prevalence of OC.  While these studies suggest an association between topiramate exposure and risk of oral clefts, the magnitude of the risk is not precisely defined.  Previous studies have calculated the risk of oral clefts to be as high as 1.5%; however, this study suggests a lower prevalence of 0.36%.

Ruta Nonacs, MD PhD

Hernandez-Diaz S.  Evidence accumulates on the association between topiramate use early in pregnancy and the risk of oral clefts.  Pharmacoepidemiol Drug Saf. 2014 Aug 12.

Margulis AV, Mitchell AA,  Gilboa SM, et al.  Use of topiramate in pregnancy and risk of oral clefts.  Am J Obstet Gynecol 2012.

Mines D, Tennis P, Curkendall SM, et al.  Topiramate use in pregnancy and the birth prevalence of oral clefts.  Pharmacoepidemiol Drug Saf. 2014 Oct;23(10):1017-25.

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