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: 9893923
• 负责人: Krista F Huybrechts
• 金额: $ 57.16万
• 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/9893923
• 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; Early Intervention; Environment; Epidemiologic Methods; Ethics; Etiology; Exposure to; Family; Fetal Development; Fetal safety; Generations; Genetic Predisposition to Disease; Health; Healthcare; Home environment; 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; Safety; Scanning; Structural defect; Teratogens; Testing; Therapeutic; Time; Universities; Woman; animal data; autism spectrum disorder; base; clinically significant; cohort; comparative; 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; 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.

项目总结/摘要 育龄妇女和孕妇使用精神药物， 在过去的十年中增加。动物模型提示了潜在的认知致畸性，但存在有限的 （大多数质量较低）至无关于人类在子宫内分娩后神经发育障碍风险的信息 接触这些药物。了解特定精神药物的作用（即， 比较安全性）、剂量和多种治疗对不良神经发育结局的影响， 给怀孕或可能怀孕的妇女开这些药物。该等资料不 根据新的妊娠和哺乳期标签规则，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， 将允许有针对性地对高危儿童进行早期干预。而某些结果可以（和 已经）在小型前瞻性队列研究、使用现有真实的- 全球数据是评估更严重和临床显著性的风险的唯一选择。 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，代表超过400万公共和私人保险 妊娠合并。关于潜在混杂变量及其代理的丰富信息， 最先进的流行病学方法将被用来仔细控制诸如共同居住和家庭等因素 环境、遗传易感性、母体营养、产前护理质量、其他妊娠暴露， 以及在母亲患有精神疾病的情况下养育子女的方法。新的方法将被用来帮助 确定妊娠期间的关键病因学窗口，其目的是划定安全期与 不安全使用。具体来说，我们将研究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 暴露于（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 这项工作建立在一个多学科研究小组的经验-布里格姆之间的合作， 妇女医院，哈佛T. H. Chan公共卫生学院和布朗大学。这些发现 这项研究将提高大量妇女的精神卫生保健质量， 在生育期间和怀孕期间患有精神疾病，因此将有一个直接的， 对公共卫生有很大影响。