Background: Topiramate (TPM) is an antiepileptic drug also used for migraine prophylaxis. Combined with phentermine, TPM is being evaluated as treatment to promote weight loss. Some observational studies have suggested an elevated risk of oral clefts in infants whose mothers used TPM in early pregnancy.
Objectives: To evaluate the association between TPM use in early pregnancy and risk of oral cleft (OC) in offspring.
Methods: We conducted the first phase of a retrospective cohort study using 1997 - 2011 automated data from four sources: HealthCore and OptumInsight (commercial insurance claims from throughout the US), Thomson Reuters (Medicaid claims from several states), and Northern California Kaiser Permanente (electronic health records). We compared the prevalence of OCs in infants of women exposed to TPM in the first trimester of pregnancy (TPM cohort) with the prevalence in two comparator cohorts: infants of women formerly exposed to TPM or other antiepileptic drugs (FE cohort) and infants of women with similar medical profiles to the TPM cohort (SMP cohort). To control for confounding, we used stratification and standardization to the TPM cohort for individual variables and propensity score decile.
Results: Overall, the birth prevalence of OCs was 0.36% (7/1945) in the TPM cohort, 0.16% (21/13,512) in the FE cohort, and 0.07% (9/13,614) in the SMP cohort. Standardized by site, the prevalence ratio (PR) for TPM vs. FE was 2.36 (95% CI: 0.99 - 5.59) and for TPM vs. SMP, 5.44 (95% CI: 2.03 - 14.61). Adjustment for other covariates one at a time yielded very similar results. Standardized by propensity score decile and site, for TPM vs. FE the PR was 2.45 (95% CI: 0.97 - 6.18) and for TPM vs. SMP, 6.46 (95% CI: 2.07 - 20.17). OC prevalence did not increase with TPM dose.
Conclusions: The preliminary results determined only from automated data in this multi-database study show first trimester topiramate exposure was associated with an elevated risk of OCs. The final analysis will rely on outcomes validated through review of medical records or longitudinal claims histories.
