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

4/5 物质暴露和早期生活逆境对儿童健康发展和结果的累积风险（行政补充）

• 批准号: 10373461
• 负责人: CHARLES Alexander NELSON
• 金额: $ 19.39万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-30 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10373461
• 关键词: Administrative Supplement; Affect; Age; Age-Months; Animal Model; Boston; Brain; COVID-19; COVID-19 diagnosis; COVID-19 pandemic; Case Study; Cells; Central Nervous System Diseases; Cerebral Palsy; Child; Child Health; Coronavirus; Data; Development; Electroencephalography; Enrollment; Environmental Risk Factor; Epigenetic Process; Event; Exposure to; Fetal Development; Funding; General Hospitals; Grant; Health; Imaging Device; Immune; Immunologic Markers; Incidence; Infant; Infant Development; Infection; Inflammation; Institutional Review Boards; Language; Learning; Life; Link; Magnetic Resonance Imaging; Massachusetts; Maternal Exposure; Measures; Mental Depression; Microglia; Modeling; Morbidity - disease rate; Mother-Child Relations; Mothers; Motor Skills; Opioid; Outcome; Parents; Participant; Pathway interactions; Pattern; Pediatric Hospitals; Perinatal; Physiological; Population; Positioning Attribute; Postpartum Depression; Pregnancy; Pregnant Women; Procedures; Protocols documentation; Psychosocial Stress; Public Health; Questionnaires; Rest; Risk; SARS-CoV-2 infection; SARS-CoV-2 positive; SARS-CoV-2 transmission; Scanning; Schizophrenia; Shapes; Social isolation; Stress; Structure; Surveys; System; Testing; Umbilical Cord Blood; Uncertainty; Vertical Disease Transmission; Visit; Visual; Water; Well in self; Woman; Zika Virus; adolescent offspring; autism spectrum disorder; behavior measurement; biobank; cohort; comparison group; congenital zika syndrome; early life adversity; effective intervention; epidemiology study; experience; fetal; follow-up; immune activation; indexing; infant outcome; inflammatory marker; language outcome; maternal stress; morphometry; neonate; neural growth; neural network; neurodevelopment; neurophysiology; neuropsychiatry; non-invasive imaging; novel; offspring; pandemic disease; parent grant; parent project; perceived stress; physical conditioning; prenatal; prenatal exposure; primary outcome; prisma; psychologic; psychological distress; recruit; relating to nervous system; resilience; response; stressor; unborn child; visual tracking; white matter

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.

项目概要/摘要 COVID-19 在全球大流行一年多以来，对身体健康和健康构成严重威胁 孕妇面临因 COVID-19 导致严重发病的风险。 特别容易受到心理困扰，再加上持续的社会孤立、经济困难 迄今为止，73,617 人对自己以及未出生的孩子的健康感到不安全和不确定。 美国孕妇的 COVID-19 检测结果呈阳性，了解产前暴露的情况。 COVID-19 和相关压力对胎儿发育的影响与公共卫生至关重要。 产前暴露于母体感染和相关压力与精神分裂密切相关 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 流行病学研究表明，感染会影响神经发育。 怀孕期间的自闭症、精神分裂症和中枢神经系统疾病的发病率较高 后代中存在疾病（例如脑瘫）（Solek et al., 2018；Knuesel et al., 2014；Bauman & Van de Water，2020）动物模型表明母体免疫激活可以改变胎儿大脑。 发育，增加神经发育风险（Bergdolt & Dunaevsky，2019）。 在多个层面上观察到压力源，包括大脑成熟破坏、表观遗传改变、 以及后代发育不良（Bick & Nelson，2016；Nelson，2020；Lupien 等人， 2019；McEwen，2012，2017；Wu 等，2020）。 感染和压力可能会加剧神经精神风险：例如，经历过精神疾病的母亲 怀孕期间的感染和压力升高更有可能使青春期的后代患有 抑郁症（Murphy 等人，2017）为了提供有效的干预措施，检查是否 – – 至关重要。 以及母亲接触 COVID-19 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 (R34 DA050289）和经批准的 IRB 协议（IRB-P00035929）来进行神经发育随访 在马萨诸塞州总医院 (MGH) 登记入住的 COVID-19 阳性女性所生婴儿的百分比 COVID-19 妊娠生物储存库（PI：Edlow）。 未来6个月，我们将招收60名母婴 从这个大群体中挑选两人参加 PI 的 BCH 实验室的两次访问（9 个月和 12 个月）。 每次访视时，我们都会进行研究程序，评估产妇压力、神经生理学（脑电图、 眼球追踪）和发育结果。一部分参与者将在 9 个月时完成 MRI 检查。

项目成果

Global, regional, and national minimum estimates of children affected by COVID-19-associated orphanhood and caregiver death, by age and family circumstance up to Oct 31, 2021: an updated modelling study.

• DOI: 10.1016/s2352-4642(22)00005-0
• 发表时间: 2022-04
• 期刊: The Lancet. Child & adolescent health
• 作者: Unwin HJT;Hillis S;Cluver L;Flaxman S;Goldman PS;Butchart A;Bachman G;Rawlings L;Donnelly CA;Ratmann O;Green P;Nelson CA;Blenkinsop A;Bhatt S;Desmond C;Villaveces A;Sherr L
• 通讯作者: Sherr L