Prenatal Exposures and Child Health Outcomes 2: A Statewide Study of Michigan Families

This project will be conducted by investigators from a coalition of Michigan institutions that participated in ECHO Cycle 1. We began with two prospective observational cohort studies—the Archive for Research on Child Health (ARCH) and the Michigan ARCH (MARCH). Participants in the ARCH cohort were enrolled at first prenatal visit, largely in Lansing, MI, between 2008 – 2016. In 2016, we expanded recruitment to create the MARCH cohort, which is a stratified random sample of births in the lower peninsula of MI. In MARCH, we aimed for a statewide sample of 1,000 births and then chose to enroll an additional 100 births in Flint, MI. As of March of 2025, 1,150 participants joined ECHO Cycle 2, including new pregnancies, with high follow-up rates (91% of core data elements, 76% of all possible biospecimens). Our aims will contribute to ECHO science by: Aim 1. Using core ECHO data, 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, in relation to child health outcomes. Aim 2. 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, examining the gut microbiome as a potential effect mediator/modifier. Aim 3. We will follow the ECHO participants from our current cohorts, continue to reconsent our ARCH and MARCH cohort participants into ECHO-2, and recruit additional pregnant women to the ECHO cohort. 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 approximately 2,200 Michigan families. 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 detailed assessments of pregnant women, their children, and conceiving partners where feasible, we will be able to make a very substantial contribution to the overall goals of the ECHO program