Project Summary This application is from a coalition of Michigan institutions that participated in the first UG3 and UH3 phases of the ECHO program. Participants in the ARCH cohort were enrolled at first prenatal visit, largely in Lansing, MI, between 2008 – 2016, 532 of whom were successfully consented for participation in ECHO, and 85% of whom are up to date on their annual follow-up visits. In 2016, we expanded recruitment to 20 additional clinics sites. We again recruited at first prenatal visit and created the MARCH cohort, which is a stratified random sample of births in the lower peninsula of MI. We aimed for a statewide sample of 1,000 births and then chose to enroll an additional 100 births in Flint, MI, and our current total MARCH study population consented to ECHO (Level 2 participants) consists of 1,084 pregnancies and 955 births. We anticipate having enrolled 1,100 pregnancies by the end of 2022, and 1,100 births by August 31, 2023. Our follow-up rates at one year (86%), two years (75%) and three years (76%) exceed what is commonly found in infant/early child follow up studies. We will further contribute to ECHO science by completing the following aims in collaboration with other ECHO cohorts: Aim 1. Using data collected in the ECHO core protocol, we will investigate the effects of a) micronutrient levels in pregnancy; b) early infancy feeding patterns and the gut microbiome; and c) early life adversity at multiple intersecting levels of maternal, family, and neighborhood stressors, all in relation to our specialized outcome, neurodevelopment. Aim 2. Using data collected in a specialized protocol, we will study the effects of mixtures of per- and polyfluoroalkyl substances (PFAS), phthalates and heavy metals in pregnancy on child body mass index, metabolic function, and neurodevelopment. In this aim as well, we will examine the gut microbiome as a potential effect mediator/modifier. Aim 3. We will follow the more than 1,600 ECHO participants from our current cohorts and recruit another 540 pregnancies to yield 450 live births consented to ECHO. We also aim to enroll approximately 225 mothers of the anticipated 450 live births for pre-conceptional data collection from whom we anticipate enrolling 67 subsequent children to produce a total study sample of some 2,200 Michigan mother/child pairs. Newly recruited pregnancies will all be from either dominantly African American cities (Detroit and Flint) or underserved rural communities in northern Michigan to contribute to the size and diversity of the overall ECHO cohort. Aim 4. We will examine preconception exposures in men that accelerate sperm epigenetic aging for their effects on offspring neurodevelopment and obesity and test the hypothesis that we can identify a signature of the extracellular preconditioned secretome in the circulating plasma of pre- conceptional women that is associated with an increased risk of recurrent preterm birth. When we have completed our recruitment and det...