Cumulative Effects of Prenatal Stress and Chemical Exposures on Child Development

项目总结 我们建议整合目前在伊利诺伊大学招聘的两个怀孕队列和 加州大学旧金山分校(UCSF)将形成一个更大的地理、社会经济、种族和 种族多元化队列(ECHO.CA.IL)，研究化学品暴露和母亲的累积影响 心理社会压力对出生结局和早期神经发育的影响。我们将重点关注两组高- 在孕妇体内定期检测到内分泌干扰物(EDCs)的产生量，这 研究表明可能会影响发育，但关于儿童健康结果的数据很少：酚类 (双酚、二苯甲酮、二氯苯酚、对羟基苯甲酸酯、三氯生、三氯卡班)和全氟烷基 物质(全氟化碳)。我们将测量慢性压力和韧性的三个指数：1)知觉-感知 家庭、邻居和工作环境中的社会地位和压力暴露；2)基于地点 -邻里层面的社会经济地位、公民参与、绿色空间和建筑环境；以及3) 生物标志物--母血和脐血白细胞端粒长度和促肾上腺皮质激素释放激素 母体血浆促肾上腺皮质激素释放激素水平。我们将测量出生结果(出生体重和胎龄)，我们 将使用创新的方法来评估基本认知功能，包括工作记忆、注意力、 幼儿和儿童早期的信息加工和社会认知。我们将处理三个具体的问题 目的：(1)评估产前暴露于EDCs与不良出生措施之间的关系 子代的结果和认知发展。(2)评价各指标之间的关系 产前应激与不良生育结局和后代认知发展的测量。 重要的是，为了这个目的，我们还将评估压力反应的生物标记物是否调节了这种关系 在知觉和基于地点的压力和发展结果之间。(3)评估母体是否 应激改变已观察到的EDC暴露与不利出生指标之间的关系 后代的结果或认知发展。在规划期间，我们将协调数据 收集和管理(包括生物检疫、压力测量和出生测量 结果和认知功能)，以便为合并我们的两个数据集和 与ECHO数据分析中心共享我们的数据。在UG3阶段，我们还将积极参与 制定和实施全回声研究议定书，提供专门知识和方法 评估母体压力、子代认知发展和我们的整合与协调经验 收集我们两个地理位置不同的怀孕队列的数据。总而言之，我们的创新研究 方法将通过提供一个框架，将累积的化学品暴露与 慢性心理社会压力和复原力来源，以了解复杂的产前 影响婴儿期和幼儿期发育结果的病因因素。

PROJECT SUMMARY We propose to integrate two pregnancy cohorts currently under recruitment at the University of Illinois and the University of California, San Francisco (UCSF) to form a larger geographically, socio-economically, racially and ethnically diverse cohort (ECHO.CA.IL) to study the cumulative impact of chemical exposures and maternal psychosocial stress on birth outcomes and early neurodevelopment. We will focus on two groups of high- production volume endocrine disrupting chemicals (EDCs) regularly detected in pregnant women, which research suggests may impact development, but for which data on child health outcomes is sparse: phenols (bisphenols, benzophenone, dichlorophenols, parabens, triclosan, triclocarban) and perfluorinated alkyl substances (PFAS). We will measure three indices of chronic stress and resilience: 1) Perceptual - perceptions of social standing and stress exposures in household, neighborhood, and work environments; 2) Place-based – neighborhood level socioeconomic status, civic engagement, green space and built environment; and 3) Biomarkers - telomere length in maternal and umbilical cord leukocytes and corticotropin releasing hormone (CRH) levels in maternal plasma. We will measure birth outcomes (birth weight and gestational age) and we will use innovative approaches to assess basic cognitive functions including working memory, attention, information processing, and social cognition in infancy and early childhood. We will address three specific aims: (1) Evaluate the relationship between prenatal exposures to EDCs and measures of adverse birth outcomes and cognitive development of offspring. (2) Evaluate the relationship between measures of prenatal stress and measures of adverse birth outcomes and cognitive development of offspring. Importantly, for this aim we will also assess whether biomarkers of stress response mediate the relationship between perceptual and place-based stress and developmental outcomes. (3) Evaluate whether maternal stress modifies observed relationships between EDC exposures and measures of adverse birth outcomes or cognitive development of offspring. During the planning period, we will harmonize data collection and management (including biospecimens, stress measurements, and measurements of birth outcomes and cognitive functions) across our two cohorts to prepare for merging our two data sets and for sharing our data with the ECHO Data Analysis Center. During UG3 stage we will also actively participate in development and implementation of the ECHO-wide study protocol contributing expertise and methodology for assessing maternal stress, offspring cognitive development and our experiences integrating and harmonizing data collection across our two geographically distinct pregnancy cohorts. In summary, our innovative research approach will contribute to ECHO by providing a framework for integrating cumulative chemical exposures with chronic psychosocial stress and sources of resilience in order to understand the complex set of prenatal etiologic factors that shape developmental outcomes in infancy and early childhood.