MONEAD Data and Statistical Center

描述（由申请人提供）：迫切需要对妊娠期癫痫妇女（WWE）进行前瞻性、适当对照研究，以改善孕产妇和儿童结局。拟议的调查与NINDS癫痫研究基准相关，并将解决最近美国神经病学学会指南所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，并建立研究团队。具体目的是：1)确定WWE是否在怀孕期间癫痫发作增加，并描述其影响因素；2)确定WWE的剖腹产率是否增加，并划定影响因素；3)确定WWE在妊娠期和产后抑郁风险是否增加，并确定危险因素；4)确定子宫内AED暴露对WWE儿童语言智力和其他神经行为结局的长期影响；5)确定WWE患儿的胎龄小及其他新生儿不良结局是否增加；6)确定服用抗癫痫药物时母乳喂养是否会损害孩子的语言智力和其他认知能力。本研究的总体目标是建立AED暴露与母亲和儿童预后之间的关系，并描述和解释AED暴露和反应的可变性。抗惊厥血药水平（ABLs）和浓度下面积-时间曲线（auc）将被用作药物暴露的直接测量。该结果将使临床医生能够前瞻性地为母亲计算个体剂量方案，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，以进一步描述患者之间的个体差异。

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.