Fetal and Neonatal Neurobehavior and Prenatal Antidepressant Exposure

描述（由申请人提供）：在美国，每年至少有60万婴儿在怀孕期间暴露于母体重度抑郁症（MDD）。胎儿暴露于母亲的重度抑郁症与新生儿的医学和神经行为缺陷以及儿童的长期情绪、行为和社会问题有关。重度抑郁症的治疗至关重要。目前，选择性5 -羟色胺再摄取抑制剂（SSRIs）和双作用5 -羟色胺和去甲肾上腺素再摄取抑制剂（SNRIs）是MDD（统称SRIs）的一线药物治疗选择。最近的研究表明，妊娠期暴露于SRIs与与成人血清素毒性或停药综合征（戒断）一致的短暂新生儿不良症状有关。我们提出的研究将解决这一领域至关重要但未知的问题——这些症状是否与血清素毒性、母体重度抑郁症暴露有关，或者它们是否构成真正的戒断综合征。拟议的研究汇集了一个由经验丰富的研究人员组成的跨学科团队，利用药物暴露模型解决有关产前暴露对婴儿健康和发育影响的关键问题。我们的研究将使用一种受控的药物暴露方法，这种方法已成功应用于其他合法和非法药物。我们计划研究四组70名妇女，每组根据她们在妊娠晚期的治疗选择：1)使用SRI /目前没有MDD标准，2)MDD/没有药物治疗，3)MDD和SRI， 4)目前没有MDD或SRI使用。精神病诊断将通过标准化的临床访谈来确定。我们将在妊娠28和36周使用超声观察和胎儿心率监测来检查胎儿的神经行为。新生儿将在第0、1、2、4、7、14和30天使用一系列神经行为评估和新生儿药物戒断评估量表进行检查，并测量睡眠、生理和行为反应性。我们将解决三个主要的具体目标：1。确定妊娠期SRI暴露对胎儿和婴儿神经行为的影响，包括新生儿期戒断。检查26至44周孕龄的神经行为发育概况，以及3。确定SRI暴露量、血清素代谢物水平和婴儿SRI血清药物水平是否与胎儿和婴儿神经行为（包括新生儿期戒断）相关。该研究汇集了一个经验丰富的多学科团队，利用药物暴露模型来解决产前血清素再摄取抑制剂（SRI）暴露对婴儿健康和发育的影响的关键问题。该模型将系统地评估产前SRI暴露导致的神经行为影响的发展，将这些影响与母亲重度抑郁症暴露相关的影响区分开来。本研究的数据将有助于制定更好的产前使用SRI药物的治疗指南，以及对出现不良症状的婴儿的治疗指南。

DESCRIPTION (provided by applicant): Each year at least 600,000 infants born in the United States are exposed to maternal Major Depressive Disorder (MDD) during gestation. Fetal exposure to maternal MDD is associated with newborn medical and neurobehavioral deficits and long term emotional, behavioral, and social problems in the child. Treatment of MDD is critical. Currently, selective serotonin reuptake inhibitors (SSRIs) and dual-action serotonin and norepinephrine reuptake inhibitors (SNRIs) are the first-line pharmacological treatment choice for MDD (collectively SRIs). Recent studies suggest that gestational exposure to SRIs is associated with transient adverse neonatal symptoms consistent with serotonin toxicity or discontinuation syndrome (withdrawal) as seen in adults. Our proposed study will address critically important but unknown issues in this area - if the symptoms are related to serotonin toxicity, exposure to maternal MDD, or if they constitute a true withdrawal syndrome. The proposed study brings together an interdisciplinary team of experienced researchers to address critical questions on the effects of prenatal exposure on infant health and development using a drug exposure model. Our study will use a controlled, drug-exposure methodology that has been successfully applied to other licit and illicit drugs. We plan to study four groups of 70 women each based on their treatment choices by the third trimester: 1) SRI use/no current MDD criteria, 2) MDD/no medication treatment, 3) MDD and SRIs and 4) no current MDD or SRI use. Psychiatric diagnoses will be determined using a standardized clinical interview. We will examine fetal neurobehavior at 28 and 36 weeks gestation using ultrasound observation and fetal heart rate monitoring. Newborns will be examined utilizing serial neurobehavioral assessments and a neonatal drug withdrawal assessment scale on days 0, 1, 2, 4, 7, 14, and 30 with measures of sleep, and physiological and behavioral reactivity. We will adress 3 main specific aims: 1. Determine the effects of gestational SRI exposure on fetal and infant neurobehavior including withdrawal in the neonatal period, 2. Examine the neurobehavioral developmental profile from 26 to 44 weeks gestational age, and 3. Determine if amount of SRI exposure, serotonin metabolite levels, and infant SRI serum drug levels are related to fetal and infant neurobehavior including withdrawal in the neonatal period.The proposed study brings together an experienced multidisciplinary team to address critical questions on the effects of prenatal Serotonin Reuptake Inhibitors (SRI) exposure on infant health and development using a drug exposure model. The model will systematically evaluate the development of neurobehavioral effects attributed to prenatal SRI exposure, distinguishing these effects from those related to maternal major depression exposure. The data from this study will lead to the development of better treatment guidelines for the prenatal use of SRI medications as well as treatment guidelines for infants demonstrating adverse symptoms.