In-utero exposure to psychotropic medications and the risk of neurodevelopmental disorders

项目摘要/摘要 在育龄妇女和怀孕妇女中使用精神药物的情况明显 在过去的十年里有所增加。动物模型显示了潜在的认知致畸作用，但这是有限的。 (主要是低质量的)到没有关于人类在子宫中发生神经发育障碍的风险的信息 暴露在这些药物中。了解特定精神药物的效果(即， 相对安全性)、剂量和综合治疗对指导神经发育不良结局很重要 给怀孕或可能怀孕的妇女开这些药物的处方。这样的信息是 鉴于新的怀孕和哺乳标签规则，对监管机构也是至关重要的。 最后，了解宫内精神药物暴露与神经发育之间的联系 障碍将允许对有风险的儿童进行有针对性的早期干预。鉴于某些结果可能(和 已经)在小型前瞻性队列研究的背景下进行了研究，使用现有的真实- 世界数据是评估更严重和临床意义更大的风险的唯一选择 神经发育结果。 我们将使用嵌套在两个国家纵向的妊娠队列来解决这些临床问题 美国的医疗保健利用数据库，代表着超过400万的公共和私人保险 怀孕加起来。关于潜在混杂变量及其替代变量的丰富信息，以及 将使用最先进的流行病学方法仔细控制合住和家庭等因素 环境、遗传倾向、产妇营养、产前护理质量、其他孕期接触情况、 以及在母亲精神疾病背景下的育儿方法。将使用新的方法来帮助 确定妊娠期的关键病因窗口，该窗口的目的是确定安全和安全的时间段。 使用不安全。具体地说，我们将检查神经发育障碍的风险--包括自闭症 谱系障碍、注意力缺陷/多动障碍和宫内发育迟缓 接触(1)情绪稳定剂和其他抗惊厥药物，(2)抗抑郁药，(3)抗精神病药物，(4) 精神刺激剂。 这项工作建立在一个多学科研究团队的经验基础上--Brigham与 以及妇女医院、哈佛大学公共卫生学院和布朗大学。调查结果 从这项研究将提高大量挣扎的女性的心理健康护理的质量 在生殖年龄段和怀孕期间患有精神疾病，因此将有直接和 对公共卫生造成很大影响。

Project Summary/Abstract The use of psychotropic medications in women of reproductive age and in pregnant women has markedly increased in the last decade. Animal models suggest potential cognitive teratogenicity, but there is limited (mostly low quality) to no information on the risk of neurodevelopmental disorders in humans following in utero exposure to these medications. Understanding the effect of specific psychotropic medications (i.e., comparative safety), dose, and polytherapy on adverse neurodevelopmental outcomes is important for guiding the prescribing of these medications to women who are or who may become pregnant. Such information is also of crucial importance to regulatory agencies in light of the new Pregnancy and Lactation Labeling Rule. Finally, understanding the connection between in utero psychotropic exposures and neurodevelopmental disorders will allow for targeted early interventions in children at risk. Whereas certain outcomes can be (and have been) studied in the context of small prospective cohort studies, large-scale studies using existing real- world data are the only option available for evaluating the risk of more severe and clinically significant neurodevelopmental outcomes. We will address these clinical questions using pregnancy cohorts nested in two national longitudinal healthcare utilizations databases in the US, representing over 4 million publicly and privately insured pregnancies combined. Rich information on potential confounding variables and their proxies, and state-of- the-art epidemiological methods will be used to carefully control for factors such as shared home and family environment, genetic predisposition, maternal nutrition, quality of prenatal care, other pregnancy exposures, and the approach to parenting in the setting of maternal mental illness. Novel methods will be used to help determine the critical etiological window during pregnancy, which the aim of delineating periods of safe versus unsafe use. Specifically, we will examine the risk of neurodevelopmental disorders — including autism spectrum disorder, attention deficit/hyperactivity disorder, and developmental delays — following in utero exposure to (1) mood stabilizers and other anticonvulsant drugs, (2) antidepressants, (3) antipsychotics, (4) psychostimulants. This effort builds upon the experience of a multidisciplinary research team - a collaboration between Brigham and Women’s Hospital, the Harvard T.H. Chan School of Public Health and Brown University. The findings from this research will improve the quality of mental health care for the large number of women that struggle with mental illness during their reproductive years and during pregnancy, and as such will have a direct and large public health impact.