A prospective study of critical environmental exposures in formative early life that impact lifelong health in rural US children: the New Hampshire Birth Cohort Study

Project Summary/Abstract: Major gaps exist in our knowledge of the health impacts of widespread anddramatically expanding exposures among children in the US. Children from rural regions are particularlyunderstudied, but may experience higher exposures to contaminants by drinking unregulated water; fromhousehold air pollution from wood stoves; and consequent to their rural and changing landscape (e.g., fromclimate change). As part of this ECHO Pediatric Cohorts application, we propose to take advantage of theNIEHS/EPA supported New Hampshire Birth Cohort Study (NHBCS): a rural, ongoing pregnancy cohort thathas accrued over 1,500 maternal-infant dyads. By the beginning of the UH3 phase of this application, theanticipated cohort size will be 2,000, and as part of this ECHO Pediatric Cohorts application, accrual will beextended to 3,000 maternal-infant pairs. Clinical outcomes are being ascertained from interval interviews,questionnaires, medical records, in-person assessments and laboratory tests. The study has archivedenvironmental (tap water and indoor air) and biological samples during pregnancy (maternal blood, urine andhair), as well as biological samples acquired at birth (infant cord blood, placenta and meconium) and duringchildhood (urine, blood, buccal cells, breast milk, toenails and stool). The ability to utilize these samples for awide range of downstream analyses has been demonstrated. For the current application, emerging hypothesesof concern will be addressed by: (1) leveragingthe extant NHBCS to perform targeted and unsupervisedmetabolomic analyses of 1,000 cord blood samples and 250 paired maternal gestational blood samples, andassess associations with exposures, early growth, and the infant microbiome; (2) expandingdata acquisition,sample collection and participant accrual to more precisely characterize exposures and timing of early lifeexposures by obtaining urinary metal metabolomic measurements, and exposome monitoring data from thefirst trimester of pregnancy, along with spatial analysis of naturally shed teeth for prenatal metalconcentrations; and (3) extending follow-up to identify childhood exposures to contaminants (throughbiomarkers and personal monitors); the home environment (e.g., physical activity and sleep patterns, foodenvironment, green, blue and white space, and media usage); and medical exposures (e.g., prescription andnon-prescription medications and surgical interventions) that relate to fetal and childhood growth, obesity atage 3 years, respiratory infection and asthma by age 5 years, and pulmonary function data at age 7.5 years.Novel statistical approaches will be used to determine the role of the intestinal and salivary microbiome asmediators of these effects. The collective expertise, methodologies, data, samples and preliminary results fromthis study will contribute to the planning of the broader ECHO Pediatric Cohorts initiative in order to advanceour understanding of the environmental factors early in life that drive childhood and lifelong health.