Fetal antiepileptic drug exposure and learning and memory functioning at 6 years of age: The NEAD prospective observational study
Fetal antiepileptic drug exposure and learning and memory functioning at 6 years of age: The NEAD prospective observational study
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DOI：
10.1016/j.yebeh.2018.12.031
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发表时间：
2019-03-01
影响因子：
2.6
通讯作者：
Zajdowicz, Thad
中科院分区：
文献类型：
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作者：
Cohen, Morris J.;Meador, Kimford J.;Zajdowicz, Thad
抗癫痫药物对神经发育的影响 (NEAD) 研究是一项在美国和英国开展的前瞻性观察性多中心研究，纳入了 1999 年至 2004 年间接受抗癫痫药物 (AED) 单药治疗的癫痫孕妇。该研究旨在确定四种常用 AED（卡马西平、拉诺三嗪、苯妥英和丙戊酸钠）是否存在差异性长期神经发育影响。在这份报告中，我们研究了 221 名 6 岁儿童（包括四对双胞胎）的胎儿 AED 暴露对学习和记忆功能的影响，这些儿童的母亲在怀孕期间服用了其中一种 AED。他们的表现与儿童记忆量表（CMS）标准化样本中正常发育的六岁儿童的全国样本进行了比较。这项研究的主要结果表明，在所有七个 CMS 指数中，接触丙戊酸的儿童的平均表现水平均显着低于正常对照组儿童的平均表现水平。除了一个例外，这一发现在分测试水平上也成立。这些发现与不显着的言语和非言语遗忘分数相结合似乎表明，作为一个群体，接触丙戊酸钠的儿童在处理、编码和学习听觉/言语以及视觉/非言语材料的能力方面经历了显着的困难。此外，他们在直接听觉工作记忆中保存和操作信息表现出很大的困难。然而，一旦学习并存储了信息，接触丙戊酸的儿童似乎能够以正常水平检索他们所学到的信息。最后，丙戊酸暴露儿童表现出的处理、工作记忆和学习缺陷与剂量相关。与丙戊酸钠相比，有关接受卡马西平、拉莫三嗪和苯妥英单一治疗的儿童的研究结果尚不清楚。因此，需要进一步研究来确定妊娠期间接受卡马西平、拉莫三嗪和苯妥英单药治疗的儿童对学习和记忆功能的潜在风险。需要采用更大规模的前瞻性研究进行更多研究，以确认在怀孕期间服用这四种 AED 的母亲对孩子的长期认知和行为风险，并描述新 AED 的任何潜在风险，并了解 AED 对未成熟大脑产生不良影响的潜在机制。 (C) 2019 Elsevier Inc. 保留所有权利。
The Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) Study was a prospective observational multicenter study in the USA and UK, which enrolled pregnant women with epilepsy on antiepileptic drug (AED) monotherapy from 1999 to 2004. The study aimed to determine if differential long-term neurodevelopmental effects exist across four commonly used AEDs (carbamazepine, larnotrigine, phenytoin, and valproate). In this report, we examine fetal AED exposure effects on learning and memory functions in 221 six-year-old children (including four sets of twins) whose mothers took one of these AEDs during pregnancy. Their performance was compared with that of a national sample of normally developing six year olds from the standardization sample of the Children's Memory Scale (CMS). The major results of this study indicate that the mean performance levels of children exposed to valproate were significantly below that of the children in the normal comparison group across all seven of the CMS Indexes. With one exception, this finding held up at the subtest level as well. These findings taken together with nonsignificant verbal and nonverbal forgetting scores appear to indicate that, as a group, children exposed to valproate experienced significant difficulty in their ability to process, encode, and learn both auditory/verbal as well as visual/nonverbal material. In addition, they exhibited significant difficulty holding and manipulating information in immediate auditory working memory. However, once the information was learned and stored, the valproate-exposed children appeared to be able to retrieve the information they did learn at normal levels. Finally, the processing, working memory, and learning deficits demonstrated by the valproate-exposed children are dose-related. In contrast to valproate, the findings pertaining to the children exposed to carbamazepine, lamotrigine, and phenytoin in monotherapy are less clear. Therefore, further research will be required to delineate the potential risks to learning and memory functions in children exposed to carbamazepine, lamotrigine, and phenytoin in monotherapy during pregnancy. Additional research employing larger prospective studies will be required to confirm the long-term cognitive and behavioral risks to children of mothers who are prescribed these four AEDs during pregnancy as well as to delineate any potential risks of newer AEDs and to understand the underlying mechanisms of adverse AED effects on the immature brain. (C) 2019 Elsevier Inc. All rights reserved.