Abstracts

Rationale: Approximately 25,000 children are born to women with epilepsy (WWE) each year in the United States alone. Children of women with epilepsy are at increased risk for poor outcomes. Our concepts of the risks are evolving. Recent research has provided new information, but many issues remain uncertain. Methods: The Epilepsy Therapy Development Project (EDTP, a not-for–profit foundation) established the Health Outcomes in Pregnancy and Epilepsy (HOPE) forum. Here we report on the consensus views of the nine international working groups comprised of 24 experts to outline the current state of knowledge and point the way toward future research. Results: Prospective pregnancy registries appear to be the most efficient way to assess the clinical teratogenic potential of newer AEDs. To date, only a few AEDs have been assessed with substantial numbers, and results have addressed only a few of the existing treatment options. Registries are variable in design, deal with different cultures, have different definitions, and have varying timing for follow-up. Lack of information about mothers, fathers, family history, seizure type, severity, AED dose/plasma levels, various potential confounds, and long-term follow-up of the child restrict usefulness of registry data. Furthermore, to date most comparisons of malformation rates have been based on all birth defects taken together. Separate risk assessments for different types of malformations are needed. Recent discovery of AED-induced neuronal apoptosis in immature animal brains raises concern, but it is unknown if similar apoptotic changes occur in humans. Each of the individual registries has weaknesses, requiring replication in multiple studies. Several reports show risks for multiple types of anomalies with valproate (particularly at high dosage); cleft lip/palate with lamotrigine; other malformations with phenobarbital. Additional large studies are needed in humans with genotyping, blinded neuropsychological testing, and volumetric MRI scans.Conclusions: Evaluation and comparison of reports on AED teratogenicity are difficult, limiting an evidence-based approach to care of WWE. While there has been considerable progress recently through pregnancy registries, there remains concern that outcome data are incomplete. The risks of malformations and adverse cognitive and behavioral outcomes remain unclear for many older AEDs, and risks for most newer AEDs are unknown. The consequences to the individual child can be severe and lifelong. There is an urgent need for investigations to address these issues, delineate the underlying mechanisms, and explain the variance seen in outcomes across AEDs and within a single AED.