Project R-15870

Prenatal and Early-life PFAS exposure and Childhood Allostatic Load (PEPCAL) (Research)

Per- and polyfluoroalkyl substances (PFAS) are environmental pollutants known to disrupt endocrine and metabolic pathways. This project investigates the impact of PFAS on children's health by analyzing two biochemical stress markers, cortisol and dehydroepiandrosterone-sulfate (DHEA-S). Using these sensitive markers, combined with cardiovascular and immune markers, the allostatic load (AL) as a subclinical indicator of later life health risks is calculated. High allostatic load is a strong predictor of cardiovascular disease mortality and is influenced by the cumulative effects of chronic stress and environmental conditions on mental and physical health. Previous research has shown associations between PFAS exposure and altered cortisol levels in adults, along with immune and metabolic changes that are linked to stress responses. However, this process remains unexplored in the context of prenatal PFAS exposure and its impact on childhood AL. By measuring non-invasively, the long-term levels of stress hormones in fingernails and hair, we can specify the primary AL biomarkers more accurately than other methods. The specific aims of this project are: 1) to develop an efficient protocol for the extraction and analytical determination of cortisol and DHEA-S in nail and hair clippings of children in the ENVIRONAGE birth-cohort, 2) to determine mixture and individual effects of internal prenatal PFAS exposure on childhood AL at 4 and 10 years, investigate the interaction with maternal prenatal stress, and calculate the population attributable fraction (PAF) of Flemish children with a high-risk AL accountable to prenatal PFAS exposure above the human biomonitoring (HBM) I threshold, 3) to investigate mediating effects of fetal programming according to the Developmental Origins of Health and Disease theory for these associations , 4) to determine effects of postnatal PFAS estimated by external exposure to tab-water and consumer products on childhood AL at 4 and 10 years. These findings provide necessary insights into biological risk factors in childhood linked with prenatal and early life PFAS exposure and shed light on underlying mechanisms of PFAS toxicity. By calculating the PAF, public health systems and policymakers are supported in their decisions about preventive measures and recommendations concerning prenatal and childhood PFAS exposure.

01 November 2025 - 31 October 2026