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: 10308018
• 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 2023-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10308018
• 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.

我们寻求利用全国大量出生群体的资源来解决重要的新问题 进展 我们对妊娠期间选择性血清素再摄取抑制剂 (SSRI) 安全性的了解对于 在美国，大约 6% 的孕妇使用 SSRIs，人数超过 200,000。 由于血清素 (5-HT) 在早期大脑发育中起着关键作用， 在此期间操纵 5-HT 水平可能会在一个大的国家中产生持久的行为后果。 在芬兰的出生队列中，跟踪至 14 岁，我们证明母亲 SSRI 暴露与 后代抑郁症和其他不良精神后果的风险增加，与母亲无关 然而，我们对母亲的长期影响的理解存在许多重大差距。 SSRIs 和后代精神疾病的研究有几个优点，包括特征明确。 出生队列、大样本量以及将母亲 SSRI 使用与后代精神病结果联系起来的能力 时间跨度超过20年。 本研究的主要目的是解决有关母亲 SSRI 暴露和 后代的精神结局，包括抑郁症和焦虑症、自闭症谱系障碍和 为此，我们将使用前瞻性出生队列研究设计。 并调查 21 岁之前暴露和未暴露的后代的精神结局发生率 子宫内的 SSRIs 并利用全国孕产妇综合数据库的登记联系 抗抑郁药物的使用、后代的精神病结果、研究评估和其他相关变量。 这些数据几乎可以在所有有权享受全民健康保险的芬兰居民中获得。 具体来说，我们应该：1）检查先前观察到的抑郁症风险是否急剧上升 青春期早期暴露于 SSRI 的母亲后代继续进入老年组 2) 使用 基于研究的访谈，是否与产前 SSRI 暴露相关的后代抑郁症比 在未暴露母亲的后代中；3) 消除母体 SSRI 使用母体贡献的歧义； 疾病严重程度、家庭负担和产后母亲精神病理学对后代精神结局的影响 4) 解决孕产妇接触 SSRI 后影响后代结局的脆弱因素，包括妊娠期 暴露时间、抗抑郁药物特征和后代性别；5) 评估是否为新生儿； SSRI 戒断引起的并发症介导 SSRI 与后代结局之间的关联。 这项研究的结果与其他小组的研究相结合，预计将提供以下信息： 目前还不足以帮助婴儿和患者就 SSRI 的使用做出更明智的决定 在怀孕期间，可能会减少有害后果，同时也降低复发的可能性。

项目成果

Maternal SSRI use during pregnancy and offspring depression or anxiety disorders: A review of the literature and description of a study protocol for a register-based cohort study.

母亲在怀孕期间使用 SSRI 会导致后代抑郁或焦虑症：基于登记的队列研究的文献综述和研究方案描述。

• 发表时间: 2023-06
• 作者: Upadhyaya, Subina;Brown, Alan;Cheslack;Gissler, Mika;Gyllenberg, David;Heinonen, Emmi;Laitinen, Joonas;McKeague, Ian;Hinkka;Sourander, Andre;Tornio, Aleksi;Malm, Heli
• 通讯作者: Malm, Heli