MONEAD Data and Statistical Center

描述（由申请人提供）：迫切需要在妊娠期癫痫（WWE）妇女中进行前瞻性、适当对照研究，以改善母婴结局。拟议的调查与NINDS癫痫研究基准有关，并将解决最近美国神经病学学会指南指出的我们知识中的多个空白。这项多中心研究将采用前瞻性、观察性、平行组、队列设计，由一个既定的研究团队进行。具体目标是：1）确定WWE是否在怀孕期间癫痫发作增加并描述促成因素; 2）确定WWE中剖腹产率是否增加并描述促成因素; 3）确定WWE是否在怀孕和产后期间抑郁风险增加并描述风险因素; 4）确定宫内AED暴露对WWE儿童的言语智力能力和其他神经行为结果的长期影响; 5）确定WWE儿童中小于孕龄和其他不良新生儿结局是否增加; 6）确定服用AED时母乳喂养是否损害儿童的语言智力和其他认知能力。拟议研究的总体目标是建立AED暴露与母亲和儿童结局之间的关系，并描述和解释AED暴露和反应的变异性。抗惊厥药血液水平（ABL）和浓度-时间曲线下面积（AUC）将用作药物暴露的直接测量指标。这些结果将使临床医生能够前瞻性地计算母亲的个体给药方案，以优化剂量并限制儿童不必要的药物暴露。此外，将收集遗传样本，这将为未来的药物遗传学研究提供宝贵的资源，以进一步描述患者的个体变异性。

DESCRIPTION (provided by applicant): 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.