Cognitive outcomes at age 3 years in children with fetal exposure to antiseizure medications (MONEAD study) in the USA: a prospective, observational cohort study.
Cognitive outcomes at age 3 years in children with fetal exposure to antiseizure medications (MONEAD study) in the USA: a prospective, observational cohort study.
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美国胎儿暴露于抗癫痫药物的儿童 3 岁时的认知结果（MONEAD 研究）：一项前瞻性、观察性队列研究。
DOI：
10.1016/s1474-4422(23)00199-0
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发表时间：
2023
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Fr
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作者：
Meador,KimfordJ;Cohen,MorrisJ;Loring,DavidW;Matthews,AbigailG;Brown,Carrie;Robalino,ChelseaP;Birnbaum,AngelaK;Voinescu,PaulaE;Kalayjian,LauraA;Gerard,ElizabethE;Gedzelman,EvanR;Hanna,Julie;Cavitt,Jennifer;Sam,Maria;Fr
背景大多数抗癫痫药物对胎儿神经发育的影响尚不清楚。我们的目的是调查胎儿暴露于常用的抗癫痫药物对神经心理学的结果在3 years.MethodsThe产妇结局和神经发育影响的抗癫痫药物（MONEAD）的研究是一项前瞻性的，观察性的，多中心的队列研究在20个专业癫痫中心在美国。我们研究了在妊娠期间（≤20周胎龄）入组的患有和不患有癫痫的女性（年龄14-45岁）及其子女的妊娠结局。3岁儿童的主要结局是盲法评估的言语指数评分，该评分是通过对差异能力量表II的词汇和言语理解子测验、学前语言量表5的表达性沟通和听觉理解子量表以及皮博迪图片词汇测验4的平均得分计算的。比较了患有和没有癫痫的妇女的孩子，并评估了药物暴露与暴露儿童结局的关系。MONEAD研究在ClinicalTrials.gov注册，NCT 0730170，正在进行中。结果在2012年12月19日至2016年1月13日期间，456名孕妇（351名癫痫患者和105名无癫痫患者）入组研究。345名儿童出生的妇女患有癫痫和106名儿童出生的妇女没有癫痫。癫痫妇女（n=284;校正最小二乘均值102.7，95% CI 101.4 - 103.9）与无癫痫妇女（n=87; 102.3，99.8 - 104.7）的儿童3岁时的言语指数评分无差异。言语指数评分降低的重要危险因素包括母亲智商、母亲教育程度、出生后焦虑、入学时胎龄、儿童性别和儿童种族。对于言语指数评分，未观察到抗癫痫药物暴露对妊娠晚期最大血药浓度的影响（n=258;调整后的参数估计值-2统计学9，95% CI -6统计学7至1.0）。然而，在二次分析中，多个认知措施，不同的medication.InterpretationWe发现胎儿暴露于较新的抗癫痫药物的儿童与未暴露的儿童之间的神经发育结果没有差异。然而，在次要分析中观察到一些依赖于胰岛素的抗癫痫药物作用。产妇产后焦虑的不利影响强调了在怀孕期间和产后对母亲进行筛查并实施干预措施的重要性。需要更多的研究来阐明这种依赖于胰岛素的效应。
BackgroundThe neurodevelopmental effects of fetal exposure to most antiseizure medications are unclear. We aimed to investigate the effects of fetal exposure to commonly used antiseizure medications on neuropsychological outcomes at age 3 years.MethodsThe Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study is a prospective, observational, multicentre cohort study at 20 specialty epilepsy centres in the USA. We have investigated pregnancy outcomes in women (aged 14–45 years) with and without epilepsy who were enrolled during pregnancy (≤20 weeks' gestational age), and their children. The primary outcome for children at age 3 years was a blindly assessed Verbal Index score, which was calculated by averaging scores on the Naming Vocabulary and Verbal Comprehension subtests of Differential Ability Scales-II, Expressive Communication and Auditory Comprehension subscales of Preschool Language Scale-5, and Peabody Picture Vocabulary Test-4. Children of women with and without epilepsy were compared, and the associations of medication exposures to outcomes in exposed children were assessed. The MONEAD study is registered with ClinicalTrials.gov, NCT0730170, and is ongoing.FindingsBetween Dec 19, 2012, and Jan 13, 2016, 456 pregnant women (351 with epilepsy and 105 without epilepsy) were enrolled into the study. 345 children were born to women with epilepsy and 106 children were born to women without epilepsy. Verbal Index scores at age 3 years did not differ for children of women with epilepsy (n=284; adjusted least-square mean 102·7, 95% CI 101·4 to 103·9) versus those without epilepsy (n=87; 102·3, 99·8 to 104·7). Significant risk factors for reduced Verbal Index scores included maternal intelligence quotient, maternal education, post-birth anxiety, gestational age at enrolment, child's sex, and child's ethnicity. For Verbal Index scores, antiseizure medication exposure effects were not seen for maximum third trimester blood concentrations (n=258; adjusted parameter estimate –2·9, 95% CI –6·7 to 1·0). However, in secondary analyses, exposure-dependent effects were present on multiple cognitive measures, which varied by medication.InterpretationWe found no difference in neurodevelopmental outcomes between children with fetal exposure to newer antiseizure medications compared with unexposed children. However, some exposure-dependent antiseizure medication effects were seen in secondary analyses. The adverse effects of maternal post-birth anxiety emphasise the importance of screening mothers during pregnancy and postpartum and implementing interventions. Additional studies are needed to clarify the exposure-dependent effects.FundingNational Institutes of Health, National Institute of Neurological Disorders and Stroke, and National Institute of Child Health and Development.