Early Life Exposures to Perfluoroalkyl Substances in Relation to Adipokine Hormone Levels at Birth and During Childhood

Background: Birth cohort studies have linked exposure to perfluoroalkyl substances (PFASs) with child anthropometry. Metabolic hormone dysregulation needs to be considered as a potential adverse outcome pathway. We examined the associations between PFAS exposures and concentrations of adipokine hormones from birth to adolescence. Methods: We studied 80 mother-child pairs from a Faroese cohort born in 1997 to 2000. Five PFASs were measured in maternal pregnancy serum and in child serum at ages 5, 7, and 13 years. Leptin, adiponectin, and resistin were analyzed in cord serum and child serum at the same ages. We fitted multivariable-adjusted generalized estimating equations to assess the associations of PFASs at each age with repeated adipokine concentrations at concurrent and subsequent ages. Results: We observed tendencies of inverse associations between PFASs and adipokine hormones specific to particular ages and sex. Significant associations with all adipokines were observed for maternal and child 5-year serum PFAS concentrations, whereas associations for PFASs measured at ages 7 to 13 years were mostly null. The inverse associations with leptin and adiponectin were seen mainly in females, whereas the inverse PFAS associations with resistin levels were seen mainly in males. Estimates for significant associations (P value <0.05) suggested mean decreases in hormone levels (range) by 38% to 89% for leptin, 16% to 70% for adiponectin, and 33% to 62% for resistin for each twofold increase in serum PFAS concentration. Conclusions: These findings suggest adipokine hormone dysregulation in early life as a potential pathway underlying PFAS-related health outcomes and underscore the need to further account for susceptibility windows and sex-dimorphic effects in future investigations.