Early-life exposure to perfluoroalkyl substances in relation to serum adipokines in a longitudinal birth cohort

Background: Per-and polyfluoroalkyl substances (PFAS) exposure has been linked to metabolic health outcomes such as obesity, and changes in adipokine hormones may be one of the underlying biological mechanisms. We prospectively evaluated the associations between prenatal and early childhood exposures to PFASs and adipo-kines in children. Material and methods: PFAS concentrations were measured in serum samples collected at birth, 18 months, and 5 and 9 years, and adiponectin, leptin, leptin receptor, and resistin were measured in serum samples collected at birth and 9 years. We used multivariable linear regression models to estimate the percent change in serum-adipokine concentrations for a doubling in serum-PFAS concentrations. The potential sex-specific effect of PFAS was assessed by including an interaction term between PFAS and sex in each model. Bayesian kernel machine regression (BKMR) was implemented to evaluate the overall effect of PFAS mixtures. Results: Significant associations with leptin, leptin receptor, and resistin at age 9 years were observed for serum-PFAS concentrations at 18 months and 5 and 9 years, whereas associations for PFAS concentrations at birth were mostly null. However, we observed a positive association between serum-PFHxS at birth and leptin receptor at birth. We found limited evidence regarding modification effect of sex on serum-PFAS concentrations. BKMR findings were consistent and suggested some significant effects of the overall PFAS mixtures at 18 months and 5 and 9 years on adipokine concentrations at 9 years. Conclusions: Given the associations of PFAS exposure with both adipokine hormones and metabolic functions, future studies should include assessment of adipokine hormones when examining PFAS-associated metabolic alterations.

Automated summary

This study found significant associations between PFAS concentrations at 18 months, 5 years, and 9 years, and levels of leptin, leptin receptor, and resistin in children at age 9. There was limited evidence of a modification effect of sex on serum PFAS concentrations. The Bayesian kernel machine regression results consistently suggested significant effects of PFAS mixtures at 18 months, 5 years, and 9 years on adipokine concentrations at 9 years.