Abstract
Developing children are particularly vulnerable to the effects of exposure to per- and polyfluoroalkyl substances (PFAS), a group of endocrine disrupting chemicals. We hypothesized that early life exposure to PFASs is associated with poor metabolic health in children. We studied the association between prenatal and postnatal PFASs mixture exposure and cardiometabolic health in children, and the role of inflammatory proteins. In 1,101 mothers-child pairs from the Human Early Life Exposome project, we measured the concentrations of PFAS in blood collected in pregnancy and at 8years (range=6-12years). We applied Bayesian Kernel Machine regression (BKMR) to estimate the associations between exposure to PFAS mixture and the cardiometabolic factors as age and sex- specific z-scores of waist circumference (WC), systolic and diastolic blood pressures (BP), and concentrations of triglycerides (TG), high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C) cholesterol. We measured thirty six inflammatory biomarkers in child plasma and examined the underlying role of inflammatory status for the exposure-outcome association by integrating the three panels into a network. Exposure to the PFAS mixture was positively associated with HDL-C and systolic BP, and negatively associated with WC, LDL-C and TG. When we examined the independent effects of the individual chemicals in the mixture, prenatal PFHxS was negatively associated with HDL-C and prenatal PFNA was positively associated with WC and these were opposing directions from the overall mixture. Further, the network consisted of five distinct communities connected with positive and negative correlations. The selected inflammatory biomarkers were positively, while the postnatal PFAS were negatively related with the included cardiometabolic factors, and only prenatal PFOA was positively related with the pro-inflammatory cytokine IL-1beta and WC. Our study supports that prenatal, rather than postnatal, PFAS exposure might contribute to an unfavorable lipidemic profile and adiposity in childhood.
Highlights
Cardiovascular disease (CVD) is the most common cause of death in adults worldwide (GBD 2017 Causes of Death Collaborators, 2018a)
The strongest dose–response associations were found for HDL-C and waist circumference (WC), while the positive association with Sys tolic blood pressures (BP) was seen in high polyfluoroalkyl substances (PFAS) mixture exposure levels (>50th percentile)
When all the PFAS in the mixture were held on the 50th percentile, prenatal per fluorohexane sulfonate (PFHxS) was negatively associated with HDL-C, prenatal PFNA was positively asso ciated with WC, and postnatal perfluorooctane sulfonate (PFOS) was positively associated with LDLC, and these were opposing directions from the overall mixture (Sup plementary Figure S2)
Summary
Cardiovascular disease (CVD) is the most common cause of death in adults worldwide (GBD 2017 Causes of Death Collaborators, 2018a). In Europe, 6% out of 19,000 2–11 year-olds had metabolic syndrome, a cluster of the CVD risk factors, and more than 30% of 3,500 13–18 yearolds had elevated blood cholesterol, blood glucose or blood pressure (Ahrens et al, 2014; Henriksson et al, 2017). Such unfavorable cardiometabolic status in early life can track through adolescents and adult hood, posing as high as five times increased risk for hypertension, dys lipidemia, diabetes and CVD (Franks et al, 2010; Juonala et al, 2011). The epidemiologic evidence of combined prenatal and postnatal PFAS exposure at environmentally relevant concentra tions remains inconsistent and with large knowledge gaps (Rappazzo et al, 2017)
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