Maternal exposure to antidepressants and psychiatric outcomes among offspring in a national birth cohort.

全国出生队列中母亲接触抗抑郁药物和后代的精神病结果。

• 批准号: 10053685
• 负责人: Alan Stewart Brown
• 金额: $ 48.19万
• 依托单位: NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-12-17 至 2022-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10053685
• 关键词: 14 year old; 21 year old; Address; Adolescence; Affinity; Age; Animals; Antidepressive Agents; Anxiety; Anxiety Disorders; Attention deficit hyperactivity disorder; Behavioral; Birth; Brain; Cesarean section; Characteristics; Childhood; Clinical Research; Cohort Studies; Data; Databases; Depressed mood; Depressive disorder; Development; Diagnosis; Disease; Dose; Exposure to; Family history of; Female; Finland; Funding; Gilles de la Tourette syndrome; Half-Life; Health Insurance; Incidence; Interview; Investigation; Knowledge; Language Disorders; Link; Long-Term Effects; Maternal Exposure; Mediating; Mental Depression; Mental disorders; Mothers; Neonatal; Neurobiology; Neurosciences; Newborn Infant; Outcome; Outcomes Research; Patients; Pharmaceutical Preparations; Play; Postpartum Depression; Pregnancy; Pregnant Women; Premature Birth; Psychopathology; Public Health; Registries; Relapse; Research; Research Design; Resources; Risk; Rodent; Role; Safety; Sample Size; Selective Serotonin Reuptake Inhibitor; Serotonin; Severities; Severity of illness; Sex Differences; Siblings; Speech Disorders; Withdrawal; Withdrawal Symptom; age group; antenatal; antepartum depression; autism spectrum disorder; base; child depression; cohort; early adolescence; experimental study; follow-up; in utero; male; maternal depression; member; neuropsychiatry; novel; offspring; population health; postnatal; prenatal; prospective; serotonin transporter; sex; virtual

We seek to leverage the resources of a large national birth cohort to address essential, novel questions aimed at providing guidance to clinicians on the management of depression during pregnancy. Advances in our knowledge of the safety of selective serotonin reuptake inhibitors (SSRIs) during pregnancy is critical to population health. In the U.S., approximately 6% of pregnant women use SSRIs, amounting to over 200,000 births per year of exposed offspring. Since serotonin (5-HT) plays a key role in early brain development, manipulation of 5-HT levels during this period can have lasting behavioral consequences. In a large national birth cohort in Finland, followed to age 14, we demonstrated that maternal SSRI exposure is associated with an increased risk of offspring depression and other adverse psychiatric outcomes independent of maternal diagnosis. However, there are many significant gaps in our understanding of the long-term effects of maternal SSRIs and offspring psychiatric disorders. The study has several strengths including the well-characterized birth cohort, a large sample size, and the capacity to link maternal SSRI use to offspring psychiatric outcomes spanning more than 2 decades. The main aim of the present study is to address novel questions on maternal SSRI exposure and offspring psychiatric outcomes, including depressive and anxiety disorders, autism spectrum disorders, and attention deficit hyperactivity disorder. For this purpose, we will use a prospective birth cohort study design and investigate the incidence of psychiatric outcomes up to age 21 in offspring exposed and unexposed to SSRIs in utero and capitalize on registry linkages of comprehensive nationwide databases on maternal antidepressant use, offspring psychiatric outcomes, research assessments, and other relevant variables. These data can be acquired in virtually all Finnish residents, who are entitled to universal health insurance. Specifically, we shall: 1) examine whether the sharp rise in risk of depression previously observed among maternal SSRI-exposed offspring in early adolescence continues into older age groups; 2) assess, using a research-based interview, whether offspring depression related to prenatal SSRI exposure is more severe than in offspring of unexposed mothers; 3) disambiguate from maternal SSRI use the contributions of maternal illness severity, familial loading, and postnatal maternal psychopathology on offspring psychiatric outcomes; 4) address vulnerability factors for offspring outcomes following maternal SSRI exposure, including gestational timing of exposure, antidepressant characteristics, and offspring sex; and 5) evaluate whether neonatal complications from SSRI withdrawal mediates associations between SSRIs and offspring outcomes. The findings of this study, in concert with research from other groups, are expected to provide information—which is insufficient at present—to help clinicians and patients make more informed decisions on the use of SSRIs during pregnancy, potentially diminishing harmful consequences while also reducing likelihood of relapse.

我们试图利用大型国家出生队列的资源来解决基本的新颖问题 旨在向临床医生提供有关怀孕期间抑郁症的指导。进步 我们对怀孕期间选择性5-羟色胺再摄取抑制剂（SSRI）的安全性的了解对于 人口健康。在美国，大约有6％的孕妇使用SSRI，总计超过200,000 每年暴露后代的出生。由于5-羟色胺（5-HT）在早期大脑发育中起关键作用，因此 在此期间，操纵5-HT水平可能会带来持久的行为后果。在一个大国 芬兰的生日队列，随后到14岁，我们证明了材料SSRI的暴露与 与母亲无关的后代抑郁症和其他不良精神病结果的风险增加 诊断。但是，我们对孕产妇的长期影响的理解有许多显着差距 SSRIS和后代精神病。这项研究具有多种优势，包括特征良好的 生日队列，样本量较大，以及将SSRI使用的材料与后代精神病结果联系起来的能力 跨越了20多年。 本研究的主要目的是解决有关母体SSRI暴露和 后代精神病结果，包括抑郁症和焦虑症，自闭症谱系障碍以及 注意缺陷多动障碍。为此，我们将使用前瞻性的出生队列研究设计 并调查直到21岁的后代暴露和出乎意料的后代的精神病结果事件 子宫内的SSRI并利用了全国性数据库的注册表联系 抗抑郁药，后代精神病结果，研究评估和其他相关变量。 这些数据几乎可以在有权获得全民健康保险的所有芬兰居民中获取。 具体而言，我们应：1）检查以前在 青少年早期的母亲SSRI-SSRI-SSRI-SSRI-STRPRING持续成年。 2）评估，使用 基于研究的访谈，是否与产前SSRI暴露有关的后代抑郁症比 意外母亲的后代； 3）对母亲SSRI的歧义使用母体的贡献 关于后代精神病结果的疾病严重程度，家庭负担和产后孕产妇心理病理学； 4） 解决Mater SSRI暴露后的后代结果的脆弱因素，包括妊娠 暴露时间，抗抑郁药特征和后代性别的时机； 5）评估是否新生儿 SSRI戒断的并发症介导了SSRI和后代结果之间的关联。这 本研究的结果与其他小组的研究一致，有望提供信息 目前不足以帮助临床医生和患者对使用SSRI的使用更明智的决定 在怀孕期间，可能会减少有害后果，同时降低退休的可能性。