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.

PROJECT NARRATIVE This research will explore the impact of exposure of mothers to endocrine disrupting chemicals and chronic stress during pregnancy on both birth outcomes and early neurodevelopment. Ultimately, the results will inform intervention strategies, including environmental and social policies that seek to eliminate the double jeopardy of chemical and social stressors on children's health.