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Superfund Research Program

Critical Effects Associated with Developmental PFAS Exposure Profiles

Project Leader: Philippe Grandjean
Grant Number: P42ES027706
Funding Period: 2022-2027
View this project in the NIH Research Portfolio Online Reporting Tools (RePORT)

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Project Summary (2022-2027)

Metabolic diseases, including obesity and type 2 diabetes, are major public health problems of multifactorial etiology, in which early-life exposures to environmental pollutants, such as per- and polyfluoroalkyl substances (PFAS), appear to play a role. In parallel, a critical effect of PFAS exposure is immunotoxicity that paves the way for immune dysfunction and infectious disease.

This project examines the role of developmental exposure profiles for these high-priority environmental pollutants and determines outcomes up to ages 5 and 14 years to allow identification of windows of susceptibility. The research team relies on two birth cohorts from the Faroe Islands, totaling more than 1,000 participants, to prospectively explore the associations between exposure profiles of PFAS and outcomes, including immune deficiencies, such as suboptimal antibody production after vaccinations, and increased frequency of infectious disease, and metabolic abnormalities, like excess adiposity, hyperlipidaemia, low bone mineral content, and prediabetes.

The researchers further evaluate the possible usefulness of clinically relevant biomarkers in serum, including cholesterol subfractions, adipocytokines, insulin-like growth factor-1. Exposure data are already available from analyses of maternal pregnancy, cord blood and postnatal serum at ages 18 months, 5 and 9 years from the oldest cohort, and clinical data, including DXA scans, are available for comparisons with age 14 years. The youngest cohort is currently being formed, with blood samples and human milk being taken during infancy for PFAS analyses to allow determination of PFAS transfer from lactation. Multiple regression analyses with adjustment for other environmental chemicals will be complemented by structural equation models and other advanced statistical methods.

Thus, this project aims to provide prevention potentials and new insights into the pathogenesis of major public health problems that are associated with early-life exposures to high-priority environmental pollutants.

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