Organophosphate flame retardants exposure during pregnancy, maternal thyroid hormone disruption and early infant cognition

项目总结-母公司UH3 OD023272 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 孕妇体内经常检测到高产量的内分泌干扰物(EDCs)， 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)评价产前各指标之间的关系 应激和测量不利的出生结果和后代的认知发展。重要的是，对于这一点 目的我们还将评估应激反应的生物标记物是否在知觉之间的关系中起中介作用。 以及基于地点的压力和发展结果。(3)评估母体应激是否改变了观察到的 EDC暴露与儿童不良生育结局或认知发育指标的关系 后代。在规划期间，我们将协调数据收集和管理(包括 生物样品、压力测量以及出生结局和认知功能的测量) 准备合并我们的两个数据集并与ECHO数据分析共享我们的数据的两组人员 中心。在UG3阶段，我们还将积极参与ECHO的开发和实施- 广泛的研究方案，为评估母体压力、后代认知能力提供专业知识和方法 发展和我们的经验整合和协调我们的两个地理位置的数据收集 不同的怀孕队列。总而言之，我们的创新研究方法将通过提供 将累积化学物质暴露与慢性心理社会压力和来源相结合的框架 复原力，以了解影响发育的一系列复杂的产前病因 婴儿期和儿童期早期的结果。

PROJECT SUMMARY – Parent UH3 OD023272 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 highproduction 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.