Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD)

描述(由申请人提供)：迫切需要对妊娠期癫痫(WWE)妇女进行前瞻性的、适当对照的研究，以改善母婴结局。建议的调查与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指出的我们知识中的多个空白。这项多中心调查将采用前瞻性、观察性、平行组、队列设计和现有的研究团队。其具体目标是：1)确定WWE是否增加了孕期癫痫发作并描绘其诱因；2)确定WWE的剖腹产率是否增加并描绘促成因素；3)确定WWE在孕期和产后期患抑郁症的风险是否增加，并确定危险因素；4)确定宫内AED暴露对WWE儿童言语智力和其他神经行为结果的长期影响；5)确定WWE儿童中小于胎龄和其他不良新生儿结局是否增加；6)确定在母乳喂养时服用AEDs是否损害儿童的言语智力和其他认知能力。这项拟议研究的总体目标是确定AED暴露与母子结局之间的关系，并描述和解释AED暴露和反应的变异性。抗惊厥血药浓度(ABL)和血药浓度时间曲线下面积(AUC)将被用作药物暴露的直接测量。这一结果将使临床医生能够前瞻性地计算母亲的个人剂量方案，以优化剂量并限制儿童不必要的药物暴露。此外，还将收集遗传样本，这将为未来的药物遗传学研究提供宝贵的资源，以进一步描绘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.