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: 10378117
• 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 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10378117
• 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; Home; Hospitals; Human; Impaired cognition; Intelligence Tests; Interdisciplinary Study; Label; Lactation; Learning Disorders; Light; Longitudinal cohort study; Magnetic Resonance Imaging; Medicaid; Mental Health Services; 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; stimulant use

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.

项目摘要/摘要 在生殖年龄和孕妇中使用精神药物的使用明显 在过去的十年中增加。动物模型提出了潜在的认知致畸性，但有限 （大多数低质量）没有关于子宫内神经发育障碍风险的信息 暴露于这些药物。了解特定精神药物的影响（即 比较安全性），不良神经发育结果的剂量和多治疗对于指导很重要 将这些药物的处方给妇女或可能怀孕的妇女。这样的信息是 鉴于新怀孕和哺乳标记规则，对监管机构的重要性至关重要。 最后，了解子宫心理暴露与神经发育之间的联系 疾病将允许对处于危险的儿童进行有针对性的早期干预措施。而某些结果可以是（并且 已经在小型前瞻性队列研究的背景下进行了研究 世界数据是评估更严重和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怀孕群体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400万的私人伤害 怀孕总和。有关潜在混杂变量及其代理的丰富信息，以及 ART流行病学方法将用于仔细控制共享家庭和家庭等因素 环境，遗传易感性，孕产妇营养，产前护理的质量，其他妊娠暴露， 以及在孕产妇精神疾病的情况下的育儿方法。新方法将用于帮助 确定怀孕期间的关键病因窗口，这是划定安全与安全期的目的 不安全的使用。特别是，我们将检查神经发育障碍的风险 - 包括自闭症 频谱障碍，注意力缺陷/多动障碍和发育延迟 - 在子宫内 暴露于（1）情绪稳定器和其他抗惊厥药，（2）抗抑郁药，（3）抗精神病药，（4） 精神刺激剂。 这项努力以多学科研究团队的经验为基础 - 杨百翰之间的合作 哈佛T.H.妇女医院陈公共卫生学院和布朗大学。发现 从这项研究中，将提高众多挣扎女性的心理保健质量 在生殖年和怀孕期间患有精神疾病，因此将有一个直接的 巨大的公共卫生影响。

项目成果

Validity of claims-based algorithms to identify neurodevelopmental disorders in children.

• DOI: 10.1002/pds.5369
• 发表时间: 2021-12
• 期刊: Pharmacoepidemiology and drug safety
• 影响因子: 2.6
• 作者: Straub L;Bateman BT;Hernandez-Diaz S;York C;Zhu Y;Suarez EA;Lester B;Gonzalez L;Hanson R;Hildebrandt C;Homsi J;Kang D;Lee KWK;Lee Z;Li L;Longacre M;Shah N;Tukan N;Wallace F;Williams C;Zerriny S;Mogun H;Huybrechts KF
• 通讯作者: Huybrechts KF

Using nationally representative survey data for external adjustment of unmeasured confounders: An example using the NHANES data.

• DOI: 10.1002/pds.4946
• 发表时间: 2020-09
• 期刊: Pharmacoepidemiology and drug safety
• 影响因子: 2.6
• 作者: Hernández-Díaz S;Bateman BT;Palmsten K;Schneeweiss S;Huybrechts KF
• 通讯作者: Huybrechts KF

Hydroxychloroquine early in pregnancy and risk of birth defects.

• DOI: 10.1016/j.ajog.2020.09.007
• 发表时间: 2021-03
• 期刊: American journal of obstetrics and gynecology
• 影响因子: 9.8
• 作者: Huybrechts KF;Bateman BT;Zhu Y;Straub L;Mogun H;Kim SC;Desai RJ;Hernandez-Diaz S
• 通讯作者: Hernandez-Diaz S

Atomoxetine in Early Pregnancy and the Prevalence of Major Congenital Malformations: A Multinational Study.

托莫西汀在妊娠早期和主要先天畸形的患病率：一项跨国研究。

• DOI: 10.4088/jcp.22m14430
• 发表时间: 2023
• 期刊: The Journal of clinical psychiatry
• 作者: Bröms,Gabriella;Hernandez-Diaz,Sonia;Huybrechts,KristaF;Bateman,BrianT;Kristiansen,EskildBendix;Einarsdóttir,Kristjana;Engeland,Anders;Furu,Kari;Gissler,Mika;Karlsson,Pär;Klungsøyr,Kari;Lahesmaa-Korpinen,Anna-Maria;Mogun,Helen

Prevalence of Mental Health Diagnoses in Commercially Insured Children and Adolescents in the US Before and During the COVID-19 Pandemic.

• DOI: 10.1001/jamanetworkopen.2023.14415
• 发表时间: 2023-05-01
• 期刊: JAMA NETWORK OPEN
• 影响因子: 13.8
• 作者: Straub, Loreen;Bateman, Brian T.;Vine, Seanna;Huybrechts, Krista F.
• 通讯作者: Huybrechts, Krista F.