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 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, including enlarging the diversity of the ECHO Cohort and contributing to ECHO-wide science.