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

我们寻求利用一个大型国家出生队列的资源来解决重要的新问题 旨在为临床医生提供孕期抑郁症管理的指导。进展 我们对选择性5-羟色胺再摄取抑制剂（SSRIs）在妊娠期间的安全性的了解， 人口健康。在美国，大约6%的孕妇使用SSRIs，总计超过20万 每年出生的受照射后代。由于5-羟色胺（5-HT）在早期大脑发育中起着关键作用， 在此期间操纵5-HT水平可能会产生持久的行为后果。在一个大的国家 在芬兰的出生队列中，随访至14岁，我们证明了母亲SSRI暴露与 与母亲无关的后代抑郁症和其他不良精神病后果的风险增加 诊断.然而，在我们对孕产妇死亡的长期影响的理解方面存在许多重大差距。 SSRIs和后代精神疾病。这项研究有几个优势，包括良好的特点， 出生队列，大样本量，以及将母亲使用SSRI与后代精神病结局联系起来的能力 跨越了二十多年。 本研究的主要目的是解决母亲SSRI暴露的新问题， 后代的精神病学结果，包括抑郁症和焦虑症，自闭症谱系障碍， 注意力缺陷多动障碍为此，我们将采用前瞻性出生队列研究设计 并调查暴露和未暴露于以下物质的后代中21岁以下精神病结局的发生率： 在子宫内使用SSRIs，并利用全国孕产妇综合数据库的登记联系 抗抑郁药的使用，后代的精神病结果，研究评估和其他相关变量。 这些数据可以在几乎所有有权享受全民健康保险的芬兰居民中获得。 具体而言，我们将：1）研究先前观察到的抑郁症风险的急剧上升是否与 母亲SSRI暴露的后代在青春期早期继续进入老年组; 2）评估，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）消除与母亲SSRI的歧义，使用母亲的贡献 疾病严重程度、家庭负荷和产后母体精神病理学对后代精神病结局的影响; 4） 解决母体SSRI暴露后后代结局的脆弱性因素，包括妊娠期 暴露时间、抗抑郁药特征和后代性别;以及5）评估新生儿是否 SSRI停药引起的并发症介导了SSRI与后代结局之间的关联。的 这项研究的结果，与其他研究小组的研究一致，预计将提供信息， 目前还不足以帮助临床医生和患者在使用SSRIs时做出更明智的决定 在怀孕期间，可能会减少有害后果，同时也减少复发的可能性。

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.