4/5 The Cumulative Risk of Substance Exposure and Early Life Adversity on Child Health Development and Outcomes (Administrative Supplement)

项目摘要/摘要 新冠肺炎全球大流行一年多来，对身体健康和 情感上的幸福。孕妇因新冠肺炎而面临严重发病率的风险，并可能 特别容易受到心理困扰，再加上持续的社会孤立、经济困难 不安全，不确定自己的健康，以及他们未出生的孩子的健康。到目前为止，73,617 美国孕妇新冠肺炎检测呈阳性。了解产前暴露如何 对于新冠肺炎和相关的应激影响，发育中的胎儿对公共健康至关重要。 产前暴露于母体感染和相关的压力与精神分裂密切相关 儿童神经发育。虽然新冠肺炎垂直传播的风险很低(黄金和 Simmons，2020)，母体免疫激活是产前暴露于 感染会影响神经发育。流行病学研究表明，孕产妇感染 怀孕期间与自闭症、精神分裂症和中枢神经系统的高发病率有关 子代的精神障碍(如脑瘫)(Solek等人，2018；Knusel等人，2014；Bauman& 范德沃特，2020)。动物模型表明，母体免疫激活可以改变胎儿的大脑 发展，增加神经发育风险(Bergdolt&Dunaevsky，2019)。母性的影响 应激源是在多个层面上观察到的，包括大脑成熟中断，表观遗传改变， 以及后代发育不良的结果(Bick&Nelson，2016；Nelson，2020；Lupien等人， 2019；McEwen，2012,2017；Vanderberg等人，2017；Wu等人，2020)。产前累积效应 感染和压力可能会加剧神经精神风险：例如，经历了 怀孕期间感染和压力增加更有可能使青春期子女患上 抑郁症(Murphy等人，2017年)。为了提供有效的干预措施，关键是要检查是否-- 以及母亲接触新冠肺炎和相关压力如何影响婴儿神经发育。 在波士顿儿童医院(BCH)，我们处于理想的位置，可以在现有资金的基础上继续发展(R34 DA050289)和经批准的IRB方案(IRB-P00035929)进行神经发育随访 在马萨诸塞州综合医院登记的新冠肺炎阳性妇女所生婴儿的比例 新冠肺炎妊娠生物信息库(PI：EDLOW)。 在接下来的6个月里，我们将招收60名母婴 来自这个大队列的二人组参加了PI的BCH实验室的两次访问(9个月和12个月大)。 在每次访问中，我们将进行研究程序，评估母亲的压力、神经生理学(EEG， 眼睛跟踪)，和发育结果。其中一部分参与者将在9个月后完成核磁共振检查。

Project Summary/Abstract Over a year into the global pandemic, COVID-19 poses serious threats to physical health and emotional well-being. Pregnant women are at risk for serious morbidity due to COVID-19 and may be particularly vulnerable to psychological distress, compounded by continued social isolation, financial insecurity, and uncertainty about their own health, as well as that of their unborn child. To date, 73,617 pregnant women in the U.S. have tested positive for COVID-19. Understanding how prenatal exposure to COVID-19 and associated stress impact the developing fetus is of critical relevance to public health. Prenatal exposure to maternal infection and related stress has been strongly associated with disrupted child neurodevelopment. Although risk for vertical transmission of COVID-19 is low (Golden & Simmons, 2020), maternal immune activation is a potential mechanism by which prenatal exposure to infection can impact neurodevelopment. Epidemiological studies have revealed that maternal infections during pregnancy are linked to higher incidence of autism, schizophrenia, and central nervous system disorders (e.g., cerebral palsy) among offspring (Solek et al., 2018; Knuesel et al., 2014; Bauman & Van de Water, 2020). Animal models suggest that maternal immune activation can alter fetal brain development, increasing neurodevelopmental risk (Bergdolt & Dunaevsky, 2019). Effects of maternal stressors are observed at multiple levels, including disrupted brain maturation, epigenetic alterations, and poor developmental outcomes among offspring (Bick & Nelson, 2016; Nelson, 2020; Lupien et al., 2019; McEwen, 2012, 2017; Vanderberg et al., 2017; Wu et al., 2020). Cumulative effects of prenatal infection and stress may exacerbate neuropsychiatric risk: for example, mothers who experienced an infection and elevated stress during pregnancy are more likely to have adolescent offspring with depression (Murphy et al., 2017). To inform effective interventions, it is critical to examine whether–– and how–– maternal COVID-19 exposure and related stress affect infant neurodevelopment. At Boston Children's Hospital (BCH), we are ideally positioned to build on current funding (R34 DA050289) and an approved IRB protocol (IRB-P00035929) to perform neurodevelopmental follow-up of infants born to COVID-19-positive women, enrolled in the Massachusetts General Hospital (MGH) COVID-19 Pregnancy Biorepository (PI: Edlow). In the next 6 months, we will enroll 60 mother-infant dyads from this large cohort to participate in two visits at the PI's BCH lab (ages 9 and 12 months). At each visit, we will conduct study procedures assessing maternal stress, neurophysiology (EEG, eyetracking), and developmental outcomes. A subset of participants will complete an MRI at 9 months.