Resilience to prenatal stress: Implications for offspring health and neurodevelopment

项目摘要 与健康和疾病的发展起源理论相一致，产前压力可以 对后代健康的持久影响，可能是与压力相关的健康问题的主要途径。 是代代相传的这种风险的传播对边缘化群体的影响尤为严重， 例如生活在资源不足社区的有色人种和家庭，他们在生活中经历了终身的不平等， 健康的社会决定因素（例如，歧视，获得医疗保健，邻里暴力）。优势- 在产前研究中缺乏基于模型的研究，并且对促孕因素的了解有限 这可能会缓冲慢性应激暴露对母体应激反应系统和胎盘的影响， 功能通过我们目前的ECHO奖进行的研究为支持 怀孕前时期是易受压力因素影响的重要窗口 健康在这次更新中，我们利用ECHO数据来检查营养状况和社会影响的程度。 支持/连通性减弱了压力源对儿童神经发育的负面影响， 和社会经济上不同的群体。我们的ECHO队列将继续招募正在进行的参与者， 匹兹堡女孩纵向研究（PGS），2,450名女性（现在年龄26-29岁）的城市人口样本， 从小就被跟踪。PGS参与者（n=568，69%黑人，27%白色，4%多种族） 在怀孕时入组ECHO研究;另外将招募609名个体， 更新期间，产生总队列1，177。广泛的孕前数据可从PGS为所有 现有和未来的ECHO参与者。在我们的社区利益相关者合作伙伴委员会的指导下，我们将实施 并提出了产前压力暴露创新、专门措施 (i.e.,母体下丘脑-垂体-肾上腺轴功能和胎盘CRH）和儿童执行功能 和应激反应，可以在ECHO队列研究中心轻松部署。因此，响应RFA-OD-22- 018，我们将推进ECHO队列解决方案导向的开发、生产和传播 合作科学具有以下具体目标：1）阐明健康和环境因素，削弱 产前压力暴露对儿童神经发育的影响; 2）检查压力之间的关联 暴露，产前应激反应和后代神经发育; 3）最大限度地保留参与者，确保 样本多样性和实现高保真ECHO协议;以及4）探索定时和累积 压力暴露对儿童健康结果的影响。我们的多元化，多学科的团队，代表广泛的 不同的身份，背景和观点，在拟议研究的各个方面都有专业知识， 非常有资格在ECHO项目的更新阶段领导协作队列科学。实现 拟议研究的既定目标将促进对具体的、可衡量的目标的了解， 预防儿童神经发育问题的方法，包括高危儿童。

PROJECT SUMMARY Consistent with the Developmental Origins of Health and Disease theory, prenatal stress can have enduring effects on offspring health and may be a major pathway through which stress-related health problems are transmitted across generations. This transmission of risk disproportionately impacts marginalized groups, such as people of color and families living in under-resourced communities who experience lifelong inequities in social determinants of health (e.g., discrimination, access to healthcare, neighborhood violence). Strengths- based models are lacking in prenatal research, and there is limited understanding of resilience-promoting factors that may buffer the impact of chronic stress exposure on maternal stress responsive systems and placental function. Research conducted via our current ECHO award has contributed to evidence supporting the preconception period as an important window of vulnerability to the effects of stressors on maternal and child health. In this renewal, we leverage ECHO data to examine the extent to which nutritional status and social support/connectedness attenuate the negative effects of stressors on child neurodevelopment across racially and socioeconomically diverse groups. Our ECHO Cohort will continue to enroll participants from the ongoing, longitudinal Pittsburgh Girls Study (PGS), an urban-population sample of 2,450 women (now ages 26-29) who have been followed since childhood. PGS participants (n=568, 69% Black, 27% White, 4% multi-racial) have been enrolled into the ECHO Study as they become pregnant; a further 609 individuals will be recruited in the renewal period, yielding a total Cohort of 1,177. Extensive preconception data are available from the PGS for all existing and future ECHO participants. Guided by our Community Stakeholder Partner Board, we will implement the ECHO Protocol with high fidelity, and propose innovative, specialized measures of prenatal stress exposure (i.e., maternal hypothalamic-pituitary-adrenal axis functioning and placental CRH) and child executive function and stress reactivity that can be readily deployed across ECHO Cohort sites. Thus, in response to RFA-OD-22- 018, we will advance the development, production, and dissemination of ECHO Cohort solution-oriented collaborative science with the following Specific Aims: 1) Elucidate health and contextual factors that attenuate the impact of prenatal stress exposure on child neurodevelopment; 2) Examine associations between stress exposure, prenatal stress reactivity and offspring neurodevelopment; 3) Maximize participant retention, ensure sample diversity and implement the ECHO protocol with high fidelity; and 4) Explore the timing and cumulative effects of stress exposure on child health outcome. Our diverse, multidisciplinary team, representing wide ranging identities, backgrounds and perspectives, has expertise in every aspect of the proposed study and is highly qualified to lead collaborative cohort science in the renewal phase of the ECHO project. Achieving the stated aims of the proposed study will advance knowledge on specific, measurable targets for tailored approaches to the prevention of neurodevelopmental problems in children, including those at highest risk.