Age-specific associations between childhood per- and polyfluoroalkyl substances exposure and blood lipid profiles: a prospective birth cohort study
Per- and polyfluoroalkyl substances (PFAS) are persistent synthetic chemicals detected in populations, including children, through exposure from food, drinking water, and consumer products. Although growing evidence links PFAS exposure to altered pediatric lipid profiles, few longitudinal studies have determined whether developmental timing during early childhood is more strongly associated with lipid alterations than exposure magnitude. Serum PFAS concentrations and lipid levels, including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG), were measured in 212 children from the Environment and Development of Children cohort at ages 2, 4, 6, and 8 years. Generalized additive mixed models (GAMMs) characterized longitudinal dose–response relationships, tested whether associations varied by exposure age, and whether baseline concentrations at age 2 years were associated with lipid trajectories from ages 2 to 8 years. Age-specific linear regression models (lagged and concurrent) and quantile-based g-computation (q-gcomp) were used to estimate age-specific associations and joint effects of the PFAS mixture on lipid levels at age 8 years. In age-pooled GAMMs at ages 2, 4, 6, and 8 years, exposure-response relationships varied in both shape and direction across PFAS compounds for all lipid outcomes, including linear, non-linear and inverse patterns. Baseline PFAS concentrations at age 2 years were not associated with the rate of age-related change in any lipid outcome from ages 2 to 8 years. By contrast, in age-specific regression models evaluating lipid levels at age 8 years, higher HDL-C was associated with PFAS exposure at ages 6 and 8 years, and most associations remained significant after false discovery rate correction. In q-gcomp analyses, the PFAS mixture was positively associated with HDL-C at age 8 years for exposures measured at ages 6 and 8 years. In age-specific analysis, childhood PFAS exposure was associated with higher HDL-C concentrations, and the strength of this association varied by exposure age rather than corresponding directly to exposure magnitude. These findings suggest that developmental timing should be considered when evaluating the effects of childhood PFAS exposure on blood lipids, and require confirmation in larger longitudinal cohort studies.