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

子宫内接触精神药物和神经发育障碍的风险

• 批准号: 10133474
• 负责人: Krista F Huybrechts
• 金额: $ 53.94万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-06-15 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10133474
• 关键词: Address; Age; Animal Model; Animals; Anticonvulsants; Antidepressive Agents; Antipsychotic Agents; Attention deficit hyperactivity disorder; Behavioral; Child; Child Rearing; Clinical; Clinical Trials; Cognitive; Cognitive deficits; Collaborations; Communication; Conflict (Psychology); Confounding Factors (Epidemiology); Data; Data Sources; Databases; Decision Making; Development; Developmental Delay Disorders; Dose; Drug Prescriptions; Early Intervention; Environment; Epidemiologic Methods; Ethics; Etiology; Exposure to; Family; Fetal Development; Fetal safety; Generations; Genetic Predisposition to Disease; Health; Healthcare; Home; Hospitals; Human; Impaired cognition; Intelligence Tests; Interdisciplinary Study; Label; Lactation; Learning Disorders; Light; Longitudinal cohort study; Medicaid; Mental Health; Mental disorders; Methods; Mood stabilizers; Motor; National Institute of Mental Health; Nature; Neonatal; Neurodevelopmental Disorder; Neurons; Orphan; Outcome; Patients; Pharmaceutical Preparations; Play; Population; Pregnancy; Pregnant Women; Prenatal care; Prospective cohort study; Proxy; Public Health; Public Health Schools; Publications; Research; Research Methodology; Residual state; Risk; Role; Scanning; Structural defect; Teratogens; Testing; Therapeutic; Time; Universities; Woman; animal data; autism spectrum disorder; base; clinically significant; cohort; comparative safety; epidemiology study; experience; health care service utilization; improved; in utero; maternal outcome; maternal risk; medication safety; mother nutrition; neonatal outcome; neuron apoptosis; neurotoxic; novel; offspring; pregnant; prenatal exposure; prescription stimulants; prospective; psychostimulant; relating to nervous system; reproductive

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.

项目概要/摘要 育龄妇女和孕妇精神药物的使用已显着减少 动物模型表明潜在的认知致畸性，但有限。 （大多质量低）没有关于子宫内人类神经发育障碍风险的信息 了解特定精神药物的影响（即， 相对安全性）、剂量和联合疗法对不良神经发育结果的指导意义重大 向怀孕或可能怀孕的妇女开这些药物的处方此类信息是。 鉴于新的怀孕和哺乳期标签规则，这对监管机构也至关重要。 最后，了解子宫内精神药物暴露与神经发育之间的联系 疾病将有助于对高危儿童进行有针对性的早期干预。 已经）在小型前瞻性队列研究的背景下进行了研究，使用现有的真实的大规模研究 世界数据是评估更严重和具有临床意义的风险的唯一选择 神经发育结果。 我们将使用嵌套在两个国家纵向中的妊娠队列来解决这些临床问题 美国医疗保健利用数据库，代表超过 400 万公共和私人保险的人 关于潜在混杂变量及其代理以及状态的丰富信息。 将使用最先进的流行病学方法来仔细控制共享房屋和家庭等因素 环境、遗传倾向、孕产妇营养、产前护理质量、其他妊娠暴露、 以及针对产妇精神疾病的养育方法将被用来提供帮助。 确定怀孕期间的关键病因学窗口，其目的是划定安全期与 具体来说，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/多动障碍和发育迟缓——子宫内随访 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，(4) 精神兴奋剂。 这项工作建立在多学科研究团队的经验之上——布里格姆和 和妇女医院、哈佛大学陈曾熙公共卫生学院和布朗大学。 这项研究将提高大量陷入困境的女性的心理保健质量 在生育年龄和怀孕期间患有精神疾病，因此将受到直接和 巨大的公共卫生影响。