Major gaps exist in our knowledge of the health impacts of widespread and dramatically expanding exposures among children in the US. Children from rural regions are particularly understudied, but may experience higher exposures to contaminants by drinking unregulated water; from household air pollution from wood stoves; and consequent to their rural and changing landscape (e.g., from climate change). As part of this ECHO Pediatric Cohorts application, we propose to take advantage of the NIEHS/EPA supported New Hampshire Birth Cohort Study (NHBCS): a rural, ongoing pregnancy cohort that has accrued over 1,500 maternal-infant dyads. By the beginning of the UH3 phase of this application, the anticipated cohort size will be 2,000, and as part of this ECHO Pediatric Cohorts application, accrual will be extended 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 archived environmental (tap water and indoor air) and biological samples during pregnancy (maternal blood, urine and hair), as well as biological samples acquired at birth (infant cord blood, placenta and meconium) and during childhood (urine, blood, buccal cells, breast milk, toenails and stool). The ability to utilize these samples for a wide range of downstream analyses has been demonstrated. For the current application, emerging hypotheses of concern will be addressed by: (1) leveragingthe extant NHBCS to perform targeted and unsupervised metabolomic analyses of 1,000 cord blood samples and 250 paired maternal gestational blood samples, and assess 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 life exposures by obtaining urinary metal metabolomic measurements, and exposome monitoring data from the first trimester of pregnancy, along with spatial analysis of naturally shed teeth for prenatal metal concentrations; and (3) extending follow-up to identify childhood exposures to contaminants (through biomarkers and personal monitors); the home environment (e.g., physical activity and sleep patterns, food environment, green, blue and white space, and media usage); and medical exposures (e.g., prescription and non-prescription medications and surgical interventions) that relate to fetal and childhood growth, obesity at age 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 as mediators of these effects. The collective expertise, methodologies, data, samples and preliminary results from this study will contribute to the planning of the broader ECHO Pediatric Cohorts initiative in order to advance our understanding of the environmental factors early in life that drive childhood and lifelong health.

Public Health Relevance

Our country has experienced unprecedented shocks in terms of the illness, death, economic hardship for many, and family stress due to the COVID-19 pandemic. Environmental exposures have also been affected, with a lowering of air pollution levels in certain areas and likely increases in certain toxic chemicals in cleaning products, personal care products, and food, which can to affect the health and development of children with disproportionately impacts on certain racial and ethnic groups at the forefront of public concern. Within ECHO, we now have the opportunity to document these changes in toxic physical and psychosocial exposures in diverse geography regions in order to draw policy-relevant lessons from this crisis.

Agency
National Institute of Health (NIH)
Institute
Office of The Director, National Institutes of Health (OD)
Type
Exploratory/Developmental Cooperative Agreement Phase II (UH3)
Project #
3UH3OD023275-05S1
Application #
10204645
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Laessig, Susan Alison
Project Start
2016-09-21
Project End
2021-08-31
Budget Start
2020-09-01
Budget End
2021-08-31
Support Year
5
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Dartmouth College
Department
Other Basic Sciences
Type
Schools of Medicine
DUNS #
041027822
City
Hanover
State
NH
Country
United States
Zip Code
03755