There is a compelling need for prospective, properly controlled studies in women with epilepsy (WWE) during pregnancy to improve maternal and child outcomes. The proposed investigations are pertinent to the NINDS Epilepsy Research Benchmarks and will address multiple gaps in our knowledge noted by the recent American Academy of Neurology guidelines. This multicenter investigation will employ a prospective, observational, parallel-group, cohort design with an established research team.
The specific aims are to: 1) Determine if WWE have increased seizures during pregnancy and delineate the contributing factors;2) Determine if C-section rate is increased in WWE and delineate contributing factors;3) Determine if WWE have an increased risk for depression during pregnancy and post-partum period and characterize risks factors;4) Determine the long- term effects of in utero AED exposure on verbal intellectual abilities and other neurobehavioral outcomes in the children of WWE;5) Determine if small for gestation age and other adverse neonatal outcomes are increased in children of WWE;6) Determine if breastfeeding when taking AEDs impairs the child's verbal intellectual and other cognitive abilities. An overall goal f the proposed research is to establish the relationship between AED exposure and outcomes in the mother and child as well as describe and explain the variability in AED exposure and response. Anticonvulsant blood levels (ABLs) and area-under-the- concentration-time-curves (AUCs) will be used as direct measures of drug exposure. The results will enable clinicians to prospectively calculate individual dosing regimens for the mother in order to optimize dosing and limit unnecessary drug exposure to the child. In addition, genetic samples will be collected, which will provide a valuable resource for future pharmacogenetics studies to further delineate individual variability across patients.

Public Health Relevance

Epilepsy is one of the most common neurological disorders affecting women of childbearing age. Poor pregnancy outcomes are increased in these women and their children. The proposed studies will increase our knowledge on multiple levels to improve care and reduce adverse outcomes in these mothers and children.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project--Cooperative Agreements (U01)
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National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
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Fureman, Brandy E
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Emory University
Schools of Medicine
United States
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Meador, Kimford J; Pennell, Page B; May, Ryan C et al. (2018) Changes in antiepileptic drug-prescribing patterns in pregnant women with epilepsy. Epilepsy Behav 84:10-14
Hernandez-Diaz, Sonia; Huybrechts, Krista F; Desai, Rishi J et al. (2018) Topiramate use early in pregnancy and the risk of oral clefts: A pregnancy cohort study. Neurology 90:e342-e351
Voinescu, P Emanuela; Park, Suna; Chen, Li Q et al. (2018) Antiepileptic drug clearances during pregnancy and clinical implications for women with epilepsy. Neurology 91:e1228-e1236
Pennell, Page B; French, Jacqueline A; Harden, Cynthia L et al. (2018) Fertility and Birth Outcomes in Women With Epilepsy Seeking Pregnancy. JAMA Neurol 75:962-969
Patorno, Elisabetta; Bateman, Brian T; Huybrechts, Krista F et al. (2017) Pregabalin use early in pregnancy and the risk of major congenital malformations. Neurology 88:2020-2025
Bank, Anna M; Stowe, Zachary N; Newport, D Jeffrey et al. (2017) Placental passage of antiepileptic drugs at delivery and neonatal outcomes. Epilepsia 58:e82-e86
Wen, Xuerong; Hartzema, Abraham; Delaney, Joseph A et al. (2017) Combining adverse pregnancy and perinatal outcomes for women exposed to antiepileptic drugs during pregnancy, using a latent trait model. BMC Pregnancy Childbirth 17:10
Kellogg, Marissa; Meador, Kimford J (2017) Neurodevelopmental Effects of Antiepileptic Drugs. Neurochem Res 42:2065-2070
Voinescu, P Emanuela; Pennell, Page B (2017) Delivery of a Personalized Treatment Approach to Women with Epilepsy. Semin Neurol 37:611-623
Pennell, Page B; Meador, Kimford J (2016) A common medication for neuropsychiatric illnesses may cause common problems in pregnancy. Neurology 86:2224-5

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