Risk of Birth Defects with Antiepileptic Drug Combos Examined
New research suggests that the antiepileptic drug (AED) topiramate, when used in combination with other AEDs (excluding valproate) may enhance its propensity to cause fetal malformation.
Researchers from Australia examined data from the Australian Pregnancy Register from 1999 to the end of 2014. The register included 1,461 pregnancies in women who had take a single AED and 484 in women who had taken two or more AEDs simultaneously.
Results showed the overall number of fetal malformations to be greater in the polytherapy group than in the monotherapy group, (8.06% vs. 5.48%; odds ratio [OR] 1.51, 95% CI, 1.05-2.25). Antiepileptic drugs combinations that did not include valproate were linked with significantly more frequent fetal malformations than pregnancies exposed to single AEDs other than valproate.
A total of 14.94% of fetal malformations were noted in the 87 pregnacies that included topiramate as part of AED combination, this is compared to 6.55% of malformations in the 397 other polytherapies that did not include topiramate. The authors suggest that this difference is significant and would indicate that topiramate acts as a teratogen in AED combinations.
In the 290 polytherapy pregnancies in which there was no valproate exposure, the malformation rate was 6.90%, higher than the 3.64% rate in 1,182 monotherapy pregnancies not exposed to valproate, and this difference was statistically significant (OR 1.96, 95% CI 1.14–3.39). This led the author's to assert that, “It therefore seemed likely that a teratogen other than valproate was involved in the increased rate of malformations that has developed with time in the AED polytherapy–exposed pregnancies.”
The results showed that levetiracetam to be an unlikely candidate for teratogenicity in AED combinations. Of the 358 AED polytherapy pregnancies with no exposure to levetiracetam the malformation rate was 8.38%, compared to 7.14% in the 126 polytherapies which had levetiracetam exposure.
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