Association between prenatal exposure to per- and polyfluoroalkyl substances and blood pressure among preschool-aged children: The moderating effect of child-age and the mediating effect of inflammatory cytokine

Our aim is to evaluate the association of prenatal exposure to per- and polyfluoroalkyl substances (PFAS) with offspring blood pressure (BP); examine the moderating effect of children's age; and the mediating effects of inflammatory cytokines. Data of 215 mother-child pairs were collected from the Guangxi Zhuang birth cohort. Levels of nine PFAS were measured during pregnancy, and offspring BP was assessed during follow-up. The associations of PFAS exposure with BP among preschool-aged children were estimated using the generalized linear model (GLM), quantile g calculation (qgcomp), and the Bayesian kernel machine regression (BKMR) model. A machine learning model based on the random forest model, the simple slope method and the JohnsonNeyman technique were used to examine interactions. A simple mediation model was used to explore the mediating effects of inflammatory cytokines on these associations.After adjusting for covariates, prenatal exposure to perfluorooctanesulfonic acid (PFOS) was positively associated with diastolic pressure (DBP) but negatively associated with pulse pressure (PP) and the pulse pressure index (PPI). A nonlinear association was found between perfluorodecanoic acid (PFDA) and DBP, PPI, and mean arterial pressure (MAP). There was an interaction between children's age and perfluoroundecanoic acid (PFUnA) exposure on PPI; there was also an interaction between children's age and high PFDA levels (≥0.631 ng/mL) on PP and PPI. However, there interactions were only significant among children in a certain age range. Additionally, serum levels of IL-6 and TNF-α explained 13.2 % and 16.7 % of the variance in the association between PFOS exposure and offspring DBP, respectively. Our study suggested prenatal exposure to PFOS and PFDA was associated with offspring BP, and these associations were moderated by children's age. IL-6 and TNF-α levels in cord serum can mediate the association between PFOS and DBP in preschool-aged children. Further research is needed to elucidate the mechanism underlying these effects.