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

项目总结/摘要 全球疫情爆发一年多来，COVID-19对人体健康构成严重威胁， 情感健康孕妇因COVID-19而面临严重发病风险， 特别容易受到心理困扰，并因持续的社会孤立、经济困难、 不安全感，对自己的健康以及未出生的孩子的健康不确定。迄今为止， 美国孕妇的COVID-19检测呈阳性。了解产前暴露 COVID-19和相关压力对发育中的胎儿的影响对公共卫生至关重要。 产前暴露于母体感染和相关的压力与中断妊娠密切相关。 儿童神经发育尽管COVID-19垂直传播的风险较低（Golden & 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， 与自闭症、精神分裂症和中枢神经系统的发病率较高有关 疾病（例如，脑瘫）（Solek等，2018年; Knueland等人，2014年;鲍曼& 货车de Water，2020）。动物模型表明母体免疫激活可以改变胎儿大脑 发展，增加神经发育风险（Bergdolt & Dunaevsky，2019）。产妇的影响 在多个层面上观察到压力源，包括大脑成熟中断，表观遗传改变， 后代的发育结果较差（Bick &纳尔逊，2016;纳尔逊，2020; Lupien等人， 2019; McEwen，2012，2017; Vanderberg等人，2017年; Wu等人，2020年）。产前的累积效应 感染和压力可能会加剧神经精神风险：例如， 感染和怀孕期间的压力增加更有可能产生青少年后代， 抑郁症（Murphy等人，2017年）。为了提供有效的干预措施，至关重要的是要检查- 以及母亲的COVID-19暴露和相关压力如何影响婴儿的神经发育。 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（R34）的基础上 DA 050289）和获批的IRB方案（IRB-P00035929）进行神经发育随访 在马萨诸塞州总医院（MGH）登记的COVID-19阳性妇女所生婴儿的数量 COVID-19妊娠生物储存库（PI：Edlow）。 在接下来的6个月里，我们将招募60名母婴 来自该大型队列的二联体参与PI的BCH实验室的两次访视（9和12个月大）。 在每次访视时，我们将进行评估母体压力、神经生理学（EEG， 眼动追踪）和发育结果。一部分受试者将在9个月时完成MRI。

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.