The outcome of altering antiepileptic drug therapy before pregnancy

We investigated the outcome of altering antiepileptic drug (AED) therapy in the year
before pregnancy on 2233 occasions in Australian women in the 20-year period of functioning
of the Raoul Wallenberg Australian Pregnancy Register (APR).

Therapy had been altered in 358 instances (16%) in the months prior to the pregnancy
(median interval: 18 weeks). Antiepileptic drug doses had been changed in 141 pregnancies
(39.4%), being decreased in 94; drugs changed in 151 (42.2%); drugs withdrawn without
replacement in 66 (18.4%) but resumed in 40 before pregnancy ended. The main drugs
involved were valproate (34%), phenytoin (16.5%), topiramate (12.6%), and carbamazepine
(11.4%). Antiepileptic drug doses were increased significantly more often (16.9% vs.
6.4%) when epilepsy before pregnancy was not controlled, and AED treatment ceased
significantly less often (13.6% vs. 24.0%). The alterations were more often made in
women with generalized epilepsies and in those whose seizure disorders were not fully
controlled in the prepregnancy year, suggesting that avoidance of teratogenicity and
achieving improved seizure control often motivated the changes.

Overall, the alterations did not result in improved rates of seizure freedom during
pregnancy, as compared with pregnancies where therapy was unchanged; however, fetal
malformation rates were lower 3.6% vs. 5.4%, but this difference did not attain statistical
significance. The same trends regarding seizure control and malformations persisted
after pregnancies involving valproate exposure were excluded.

In conclusion, this analysis of the APR cohort did not demonstrate that altering AEDs
before pregnancy produced a significant improvement in seizure control and the reduction
in fetal malformation rate that occurred was not statistically significant.

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