Approximately 1.1 million women with epilepsy are of childbearing age in the United States and give birth to over 20,000 babies each year. Pregnancy in women with epilepsy is accompanied by increased adverse neonatal outcomes, and approximately 28% of women will experience increased seizures. Serum concentrations of most of the AEDs decline during pregnancy, but findings from previous studies are too inconsistent to provide guidelines for management of AEDs during pregnancy. The primary objectives of Project 1 are: 1) pharmacokinetic/pharmacodynamic (PK/PD) modeling of antiepileptic drugs (AEDs) during pregnancy and lactation in women with epilepsy to define fetal/neonatal exposure; 2) identifying the predictors of seizure worsening during pregnancy and postpartum. Given that both AEDs and maternal seizures have been identified as having deleterious effects on the developing fetus and neonate, the PK/PD modeling combined with the course and predictors of illness will provide the foundation to propose guidelines to reduce exposure to both seizure activity and medication. PK/PD modeling of each of the AEDs encountered will be performed in Core A. Both a traditional, two-stage approach and population PK modeling will be employed. The influence of gestational age and other demographic, genetic, and environmental factors (covariates) will be analyzed. Frequency of seizures by type will be documented throughout pregnancy and first postpartum year and compared to each woman's preconception baseline. Worsening of seizure frequency will be correlated with potential predictors, including change in serum AED concentrations, hormonal status, stress, and altered sleep patterns.
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