Abstracts

Rationale: Studies have consistently demonstrated that specific anti-epileptic drugs (AEDs) increase the risk for structural and neurodevelopmental teratogenicity, often in a dose-dependent manner. Women with epilepsy (WWE) of childbearing age require careful reconsideration of their antiepileptic drug (AED) type and dose, given that the maternal benefits of treatment during potential future pregnancies should be weighed against adverse effects on the developing fetus. There is hesitancy to change a working AED regimen, fearing a worsening of seizure control. Little data is available to provide evidence-based predictions of the risk of seizure worsening for decision-making by the provider and the patient. Too often not switching AEDs leads to exposing future offspring to undue risk.  Methods: We designed a retrospective study to quantify the risk of failure (requiring a further regimen change after the initial modification) in altering the AED regimen for reproductive safety and identify the causes behind the failure. WWE of child-bearing age who had a change in their type or dose of AED for improved reproductive safety profile prior to conception were identified through retrospective chart review among: 1) patients referred to the BWH Obstetric Epilepsy subspecialty clinic for pre-conception counseling or management during pregnancy; 2) WWE of childbearing age seen in the BWH Epilepsy clinic between 2010 and 2015. Results: In reviewing the first 97 charts from the BWH Obstetric Epilepsy clinic, we identified 24 WWE (24.7%) who underwent 27 AED regimen changes. Four (15%) of these 27 alterations in AED regimen failed with two (7%) due to increased seizure frequency/severity, and the other two for intolerable side effects (SE). Despite the initial failed switch, all four WWE had a successful optimization of their regimen: 2 transitioned to another AED, 1 was able to discontinue all AEDs, and 1 had another AED added with a final regimen of two AEDs with favorable teratogenicity profile. Additional patients seen in the BWH Epilepsy clinics between 2010 and 2015 have been identified and are being analyzed.  Conclusions: Many WWE of reproductive age may require an AED regimen adjustment to lower teratogenic risks during future pregnancies. Our preliminary data suggest that they have a high likelihood of successfully switching their AED regimen. A failed first switch is not a predictor of failure for a subsequent switch. Potential covariates (e.g., type of AED, seizure types and frequency) that increase the risk of switch failure are being analyzed.Future directions: We hypothesize that WWE undergoing an AED switch for enhanced reproductive safety will have a higher, but measurable, rate of seizure worsening compared to a matched control population without an AED switch. Towards this goal, we are currently conducting a prospective, observational, parallel-group, switch-control study with daily seizure diary tracking for 6 months and follow-up phone calls at 3 and 6 months.  Funding: Susan Spencer Clinical Research Training Fellowship through AES/AAN