Objective: To study interactions between first-trimester exposure to antidepressant drugs (ADDs) and antiepileptic drugs (AEDs), and a history of clinical depression and/or anxiety, on pregnancy outcomes and seizure control in pregnant women with epilepsy (WWE).
Methods: We examined data from the Australian Pregnancy Register of Antiepileptic Drugs in Pregnancy, collected from 1999 to 2016. The register is an observational, prospective database, from which this study retrospectively analyzed a cohort. Among the AED-exposed outcomes, comparisons were made among 3 exposure groups: (1) pregnancy outcomes with first-trimester exposure to ADDs; (2) outcomes with mothers diagnosed with depression and/or anxiety but who were not medicated with an ADD; and (3) those with mothers who were not diagnosed with depression and/or anxiety and were not medicating with ADD. Prevalence data was analyzed using Fisher's exact test.
Results: A total of 2124 pregnancy outcomes were included in the analysis; 1954 outcomes were exposed to AEDs in utero, whereas 170 were unexposed. Within the group of WWE taking AEDs, there was no significant difference in the prevalence of malformations in infants who were additionally exposed to ADDs (10.2%, 95% confidence interval [CI] 3.9-16.6), compared to individuals in the non-ADD-medicated depression and/or anxiety group (7.7%, 95% CI 1.2-14.2), or those without depression or anxiety (6.9%, 95% CI 5.7-8.1; P = 0.45). The malformation rates in pregnancy outcomes unexposed to AEDs were also similar in the above groups (P = 0.27). In WWE medicated with AEDs and ADDs, the frequency of convulsive seizures (P = 0.78), or nonconvulsive seizures (P = 0.45) throughout pregnancy, did not differ across comparative groups.
Significance: Co-medicating with ADDs in WWE taking AEDs does not appear to confer a significant added teratogenic risk, and it does not affect seizure control.
Keywords: antiepileptic drugs; anxiety; birth defects; congenital malformations; depression; seizure control.
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