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

摘要 未经治疗的抑郁症和选择性5-羟色胺再摄取抑制剂(SSRIs)的风险 治疗给20%患有产前疾病的孕妇带来了严重的两难境地。 抑郁症和他们的临床医生。产前抑郁和SSRI都被发现会对胎儿产生不利影响 大脑发育。然而，关于儿童神经发育结局的有限流行病学研究 子孙后代受到严重的方法学限制，因此，文献没有定论。建议进行的研究 解决了这些方法限制，并利用Kaiser Permanente North California(KPNC) 独一无二的通用围产期抑郁症筛查计划，以汇集32万名纵向出生队列 2013-2020年间出生的0至8岁儿童。作为标准产前护理的一部分，妇女 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)，提供了大量的 妊娠期抑郁症妇女队列及其严重程度测量。此外，KPNC的 全球儿童发育筛查计划为神经发育提供系统的筛查 精神错乱。主要结果将是DSM 5中定义的六种神经发育障碍诊断： 智力残疾、全球发育迟缓、运动障碍、沟通障碍、自闭症谱系 障碍和注意力缺陷/多动障碍(ADHD)；对应的诊断代码为 从KPNC的电子健康记录(EHR)中确定，并通过链接到加州的 发展服务部。我们将使用KPNC EHR来确定重要信息 混淆因素并链接到父亲的医疗记录，以确定有关精神病史的信息。我们将测试 假设潜在的产前抑郁和SSRI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不同而不同。我们将评估未经处理的产前治疗的效果 抑郁，与没有产前抑郁对后代的六个神经发育结果的影响相比， 在对混杂因素进行调整后。我们还将评估妊娠期使用SSRIs治疗对 子代的神经发育结果与未治疗的产前抑郁和治疗的比较 只接受心理治疗，同时考虑抑郁症的严重程度和其他混杂因素。最后，为了 研究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- 1岁的儿童(从以下四个暴露类别中的每一个中随机选择500人：无产前抑郁， 未经治疗的产前抑郁症，使用SSRIs治疗，仅使用心理治疗)以确定 通过与父母面谈，了解神经发育结果可能不符合 临床诊断，但可能需要监测和/或提供早期干预。由此得出的结论 这项研究将对公共卫生和临床产生重大影响，因为它提供的信息可以 孕妇和临床医生在做出治疗决定时立即使用。

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.