Gestational and Childhood Exposure to Per- and Polyfluoroalkyl Substances and Children’s Cardiometabolic Risk at Age 12 Years

Abstract

Background/Aim: Per- and polyfluoroalkyl substances (PFAS) may adversely influence cardiometabolic risk by activating peroxisome proliferator-activated receptors and increasing cortisol levels. We examined the influence of gestational and childhood PFAS exposure on adolescent cardiometabolic risk. Methods: We quantified concentrations of four PFAS- (perfluorooctanoate [PFOA], perfluorooctane sulfonate, perfluorononanoate, and perfluorohexane sulfonate [PFHxS])- in sera collected during pregnancy, at birth, and at ages 3, 8, and 12 years for 221 mother-child pairs in the HOME Study (Cincinnati, Ohio). We assessed cardiometabolic outcomes using biological markers (after overnight fasting) and dual-energy X-ray absorptiometry scans at age 12 years. Overall cardiometabolic risk was assessed by summing population-specific standardized z-scores for homeostatic model assessment of insulin resistance (HOMA-IR), triglyceride to high-density lipoprotein ratio, adiponectin to leptin ratio (multiplied by -1), systolic blood pressure, and percent visceral fat. We used multiple informant models to estimate covariate-adjusted associations of serum PFAS concentrations (log2-transformed) at each visit with overall cardiometabolic risk score and its individual components, tested for differences in associations across visits. Results: Gestational and cord blood PFOA concentrations were positively associated with cardiometabolic risk score (gestational β=0.7, 95% confidence interval [CI]=0.0, 1.4; cord β=0.8, 95%CI=0.0, 1.6). In contrast, PFOA concentrations at other visits were not associated with cardiometabolic risk score (P for heterogeneity across visits=0.03). The positive associations for gestational PFOA were mainly driven by HOMA-IR (β=0.3; 95% CI: 0.1, 0.5), adiponectin/leptin ratio (β=-0.5; 95% CI: -1.0, 0), and percent visceral fat (β=2.6%; 95% CI: 0.4, 4.8). Similarly, gestational and cord PFHxS were associated with higher cardiometabolic risk score (βs [95%CIs]: gestational 0.8 [0.2, 1.4]; cord 1.0 [0.3, 1.7]), and the associations were driven by the similar individual components. No effect measure modification by child sex was identified. Conclusions: Gestational PFOA and PFHxS exposure are moderately associated with unfavorable cardiometabolic risk in children at age 12 years.