Neurodevelopmental Effects of Antiepileptic Drugs II

拟议的调查是正在进行的NEAD研究的继续，该研究解决了妇女及其子女的重要卫生保健问题。抗癫痫药物（AED）在育龄妇女中用于癫痫和其他适应症（例如，疼痛和精神障碍）是常见的，但医生需要更多的数据，这是至关重要的，以充分建议和指导治疗这些妇女。动物研究已经清楚地表明，常用的AED损害行为神经发育。人类这种认知和行为缺陷的潜在后果在个人和社会成本方面都是严重的。然而，在该提案所要解决的以下问题上存在争议。最常用的抗癫痫药物是否对宫内暴露儿童的神经行为结局有不同的影响？本研究的主要目的是区分四种最常用的AED在治疗癫痫女性中的相对风险/获益，即在子宫内暴露于AED单药治疗（卡马西平、拉莫三嗪、苯妥英或丙戊酸盐）后儿童的神经行为发育。NEAD研究是一项前瞻性、平行组、队列设计、多中心研究。NEAD研究的主要优势在于它招募了一个由323对怀孕期间的母亲/儿童组成的大型独特队列，并收集了可能影响神经行为结果的因素的前瞻性数据。主要结果变量是儿童的智商分数和6岁时神经行为发育的其他指标。这项补助金的延长旨在跟踪儿童到6岁，届时神经行为测量可以预测学校表现和最终的成人智商。已经并将采集样本用于未来的药物遗传学研究。NEAD研究有一个非常宝贵的队列，这项延续建议的结果将影响接受这些药物的妇女的临床管理，并改善其子女的健康。

The proposed investigation is a continuation of the ongoing NEAD study, which addresses an important health care issue for women and their children. The use of antiepileptic drugs (AEDs) in women of childbearing age for epilepsy and for other indications (e.g., pain and psychiatric disorders) is common, but physicians need additional data, which are critical to adequately advise and direct treatment in these women. Animal studies have clearly demonstrated that commonly employed AEDs impair behavioral neurodevelopment. The potential consequences of such cognitive and behavioral deficits in humans are severe in terms of both personal and societal costs. However, controversy exists on the following issue to be addressed by this proposal. Do the most commonly used AEDs have differential effects on neurobehavioral outcomes in children exposed in utero? The primary objective of this study is to differentiate the relative risks/benefits of the four most commonly used AEDs in the treatment of women with epilepsy in terms of their children's neurobehavioral development after in utero exposure to AED monotherapy (carbamazepine, lamotrigine, phenytoin, or valproate). The NEAD study is a prospective, parallel-group, cohort design, multicenter investigation. The major strength of the NEAD study is that it has enrolled a large and unique cohort of 323 mother/child pairs during pregnancy and collected prospective data on factors, which could affect neurobehavioral outcome. The primary outcome variables are IQ scores of the children and other measures of neurobehavioral development at 6 years/old. This grant extension is designed to follow the children to 6 years/old at which time neurobehavioral measures predict school performance and ultimate adult IQ. Samples have and will be collected for future pharmacogenetic investigations. The NEAD study has an invaluable cohort, and the results of this continuation proposal will impact the clinical management of women receiving these medications, and improve the health of their children.