Comparing the Effects of Prenatal Depression and its Treatment on Developmental Outcomes of the Offspring

摘要 与未经治疗的抑郁症和选择性5-羟色胺再摄取抑制剂（SSRIs）相关的风险 治疗对20%患有产前疾病的孕妇来说是一个重大的困境。 抑郁症及其临床医生。产前抑郁症和SSRIs都被发现对胎儿有不利影响 大脑发育然而，关于儿童神经发育结局的流行病学研究有限， 后代遭受严重的方法上的限制，因此，文献是不确定的。拟定研究 解决了这些方法上的局限性，并利用了Kaiser Permanente北方加州的（KPNC） 独特的普遍围产期抑郁症筛查计划，以收集> 320，000的纵向出生队列 2013年至2020年期间出生的0至8岁儿童。作为标准产前护理的一部分， 在怀孕期间进行两次抑郁症筛查（第一次产前检查和26-28周）， 抑郁症妇女队列及其在整个怀孕期间的严重程度测量。此外，KPNC的 儿童全面发育筛查计划提供系统的神经发育筛查， 紊乱主要结局将是DSM 5中定义的六种神经发育障碍诊断： 智力残疾、全面发育迟缓、运动障碍、交流障碍、自闭症谱系 注意力缺陷多动障碍（ADHD）;相应的诊断代码将是 从KPNC的电子健康记录（EHR）中确定，并通过与加州的 发展服务部。我们将使用KPNC EHR来确定重要信息 混杂因素，并与父亲的医疗记录联系起来，以确定精神病史的信息。我们将测试 假设潜在的产前抑郁症和SSRIs是不良反应的独立危险因素， 神经发育结果，可能因婴儿性别而异。我们将评估未经治疗的产前 抑郁症，与没有产前抑郁症的后代的六个神经发育结果相比， 调整混杂因素后。我们还将评估妊娠期间使用SSRIs治疗对 与未经治疗的产前抑郁症和治疗相比， 仅用心理治疗，同时考虑抑郁症的严重程度和其他混杂因素。最后为 检查它们对不太严重的神经发育结果的影响，我们将招募2,000名5- 岁的儿童（从四个暴露类别中的每一个中随机选择500名：没有产前抑郁症， 未经治疗的产前抑郁症，用SSRIs治疗，仅用心理疗法治疗），以确定 通过对可能不符合标准的神经发育结果的父母访谈获得的信息， 临床诊断，但可能表明需要监测和/或提供早期干预。时发现的问题 研究将通过提供信息， 立即被孕妇和临床医生用于治疗决策。

ABSTRACT The risk associated with both untreated depression and selective serotonin reuptake inhibitors (SSRIs) treatment has presented a significant dilemma to the 20% of pregnant women suffering from prenatal depression and their clinicians. Both prenatal depression and SSRIs have been found to adversely impact fetal brain development. However, the limited epidemiologic research on neurodevelopmental outcomes of the offspring suffers severe methodological limitations and thus, the literature is inconclusive. The proposed study addresses these methodological limitations and leverages Kaiser Permanente Northern California’s (KPNC’s) unique universal perinatal depression screening program to assemble a longitudinal birth cohort of >320,000 children from 0 to 8 years of age born between 2013-2020. As part of standard prenatal care, women are screened for depression twice during pregnancy (at the first prenatal visit and 26-28 weeks) providing a large cohort of women with depression and its severity measures throughout pregnancy. In addition, KPNC’s universal childhood developmental screening program provides systematic screening for neurodevelopmental disorders. The primary outcomes will be six neurodevelopmental disorder diagnoses defined in the DSM 5: intellectual disability, global developmental delay, motor disorders, communication disorder, autism spectrum disorder, and attention-deficit/hyperactivity disorder (ADHD); corresponding diagnosis codes will be ascertained from KPNC’s electronic health records (EHR) and supplemented through linkage to California’s Department of Developmental Services. We will use KPNC EHRs to ascertain information on important confounders and link to the father’s medical records to ascertain information on psychiatric history. We will test the hypothesis that the underlying prenatal depression and SSRIs are independent risk factors for adverse neurodevelopmental outcomes and may differ by infant sex. We will evaluate the effect of untreated prenatal depression, compared to no prenatal depression on the six neurodevelopmental outcomes of the offspring, after adjusting for confounders. We will also assess the effects of treatment with SSRIs during pregnancy on neurodevelopmental outcomes of the offspring compared to both untreated prenatal depression and treatment with psychotherapy only, while taking into account depression severity and other confounders. Finally, to examine their impact on less severe neurodevelopmental outcomes we will recruit a subsample of 2,000 5- year old children (500 randomly chosen from each of four exposure categories: no prenatal depression, untreated prenatal depression, treatment with SSRIs, treatment with psychotherapy only) to ascertain information through parent interview on neurodevelopmental outcomes that may not meet the criteria of a clinical diagnosis, but may suggest a need to monitor and/or provide early interventions. Findings from this study will have significant public health and clinical implications by providing information that can be immediately used by pregnant women and clinicians making treatment decisions.