PROJECT SUMMARY Evidence from epidemiologic studies demonstrates the negative effects of both chronic and acute stress during gestation. These effects may occur perinatally or later in the child's life. The COVID-19 global pandemic has led to unprecedented mass disruption of social and financial security as well as changes in medical care delivery. These conditions are causing elevated levels of distress even for portions of the population that may have previously been protected from psychosocial stress. Of particular concern for pregnant women and their children, there may be direct biological effects related to infection with SARS-CoV-2 as well as substantial indirect psychosocial effects during critical periods of development with long-lasting impact on children relevant to the Environmental Child Health Outcomes (ECHO) program. This proposal addresses how psychosocial stress related to the COVID pandemic may impact perinatal and neurodevelopmental outcomes. Furthermore, evidence suggests that psychosocial stress is associated with both the gastrointestinal and vaginal microbiomes. Therefore, we will determine if maternal microbiomes or infant microbiomes mediate the impact of psychosocial stress on perinatal and neurodevelopmental outcomes. In aim 1, we address the maternal microbes and their role in mediating perinatal outcomes caused by maternal psychosocial stress during pregnancy. In aim 2, we focus on maternal psychosocial stress and its impact on neurodevelopment as mediated by the changes to the infant microbiota. We will examine these objectives in the context of our ongoing work, and as an extension of the parent grant (UG3/UH3OD023285, Paneth), where our organizing principle is that for many environmental exposures the most sensitive period of risk for child health is pregnancy and the perinatal period. The parent grant explores three primary exposures: toxic, nutritional, and inflammatory in a stratified random sample of state births recruited in the first trimester of pregnancy. Of the planned 1,100 new enrollments of cohort dyads into ECHO, more than 700 pregnant women have been consented, and, with a 75% follow up rate, more than 400 children have already been seen in infancy. Over 300 women are expected to be enrolled during the project period. While this research will leverage the local ECHO cohort, the project is designed to engage ECHO team science through two distinct but complementary ECHO-wide projects: (1) incorporation of data from two cohorts (O'Conner & Deoni) to address the aims proposed above and (2) provision of data and biospecimens to separate COVID supplement (Transande) which addresses SARS-CoV-2 seropositivity/COVID illness as well as psychosocial stress (assessed via questionnaire and cortisol measured in hair) as they relate to shortened gestation and other perinatal outcomes. Our efforts will not only inform the specific hypotheses being tested but will also inform “touch-free” methods for sample collection...