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Abstract
Over a million women with epilepsy are of childbearing age in the USA and require careful consideration of not only type of antiepileptic drug (AED) but also dosage, in the event of a planned or unplanned pregnancy. Careful selection of AEDs can lower the potential adverse effects of AEDs while maintaining seizure control for the health of not only on the patient, the mother, but also the unborn fetus. The number of treatment options has increased significantly in the last 20 years and remarkable progress has been made in characterizing the risks AEDs pose to pregnant women and fetuses. There are now robust data on teratogenesis, a growing body of data on neonatal/obstetrical outcomes and on neurodevelopmental problems associated with each AED, and some data about seizure control during pregnancy. Based on clinical evidence so far, levetiracetam and lamotrigine have emerged as the safest during pregnancy, although others may also be suitable. Despite being a common belief, not all polytherapy combinations may be detrimental, especially when avoiding valproate and topiramate. Here, we review the available clinical research, highlighting recent findings and provide thoughts for future directions in the field.
Financial & competing interests disclosure
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.
No writing assistance was utilized in the production of this manuscript.
Seizure freedom rate during pregnancy is higher in women with epilepsy (WWE) with generalized epilepsies (73.6%) than in those with localization-related epilepsy (59.5%).
Seizure control prior to pregnancy is the best predictor for seizure control during pregnancy: approximately 90% of WWE remain seizure-free during pregnancy if seizure-free for at least 9 months to 1 year prior to pregnancy, while WWE who had seizures in the pre-pregnancy month had 15-times higher risk for seizures during pregnancy.
A parental history of major congenital malformations (MCM) increases its risk more than fourfold; a history of fetal malformations in a previous pregnancy on the same antiepileptic drug leads to more than 15-fold increased risk.
Based on clinical evidence so far, levetiracetam and lamotrigine seem to have the safest profile for MCM risk, neonatal and neurodevelopmental outcomes.
Valproate is recommended to be used only as a last resort after other antiepileptic drug trials have failed, given increased MCM rates and detrimental impact on long-term neurodevelopement, including increased risk for autism.
Topiramate should also be used cautiously given reproducible evidence of increased risk for MCM, fetal growth restriction and potentially negative impact on neurodevelopment.
If polytherapy is necessary, the MCM outcomes are likely to be better if the combination chosen does not include valproate or topiramate.