Prenatal and postnatal exposure to per- and polyfluoroalkyl substances (PFAS) and cardiometabolic profile in children from six European cohorts.

Abstract

Developmental low-dose exposures to PFASs have been linked to reduced birth weight and impaired immune function, while there is less consistent evidence on obesogenic effects, insulin resistance, high blood pressure, dyslipidemia, and the composite metabolic syndrome in children. In 1089 mother-child pairs from six European birth cohorts, we examined the association between prenatal and postnatal exposure to PFAS and a composite metabolic syndrome score (MetS score) and its components: waist circumference, systolic and diastolic blood pressure (BP), HDL cholesterol (HDL-C), triglycerides and insulin. Maternal concentrations of perfluorooctanoate (PFOA), perfluorononanoate (PFNA), perfluorohexane sulfonate (PFHxS) and perfluorooctane sulfonate (PFOS) were measured in blood collected during pregnancy and child PFOA, PFNA, perfluoroundecanoate (PFUnDA), PFHxS and PFOS in samples collected at the 8-years follow-up (age range: 6-12 years). All PFAS concentrations were log-transformed and the outcomes were gender and age standardized z-scores. We applied Bayesian Kernel Machine Regression (BKMR) to examine exposure-outcomes associations. Pre- and post-natal exposure to a mixture of PFASs was negatively associated with the MetS score, insulin and waist circumference and positively associated with HDL-C and systolic BP. When exposure of the PFAS mixture was at the 75th percentile vs 25th percentile, the reduction in MetS score was -0.39 (95%CI=-0.67,-0.12), in insulin z-score -0.12 (95%CI=-0.23,-0-01), in waist circumference z-score -0.20 (95% CI=-0.39, -0.07). Postnatal PFOA and PFNA were the main contributors in the derived PFAS mixture, as shown by the high posterior inclusion probabilities (PIPs>0.50). The corresponding increase in HDL-C and systolic BP z-scores when comparing the PFAS exposure at the 75th percentile vs. 25th percentile was 0.20 (95% CI=0.00,0.40) and 0.35 (95% CI=0.04, 0.67), respectively. Our results indicate that developmental exposure to PFASs is associated with lower cardiometabolic risk. The underlying role of inflammatory and lipid regulation pathways will also be studied.