IntroductionPerfluoroalkyl substances (PFAS) are synthetic chemicals used in industrial and consumer goods that are widely detected in human populations and are associated with adverse health outcomes, including perinatal health risks and child health. One mechanism of influence may be the impact of PFAS exposure on placental structure and function. ObjectivesThe objective of this study is to investigate the relationship between maternal prenatal exposure to PFAS and measures of placental vascularization, and to assess whether changes in vascularization play a role in mediating the impact of PFAS on birth outcomes. MethodsUsing data from a prospective cohort study, we examined associations between second trimester PFAS (individually and as mixtures using Bayesian kernel machine regression) and placental arterial vasculature in term placentae (N = 158); secondarily we evaluated the degree to which alterations in placental arterial vasculature explained associations between PFAS exposure and birth outcomes. Placental arterial vasculature features were collected from arterial tracings of each placental image. ResultsIn both linear regression and mixture models, natural log-transformed perfluorooctanoic acid concentrations were negatively associated with surface vasculature, indexed by the mean distance from arterial end point to perimeter (β = −0.23, 95% CI: −0.41, −0.041); additionally, maximum arterial tortuosity was negatively associated with placental weight (β = −0.19, 95% CI: −0.34, −0.051). There were no reliable differences in effect by fetal sex. DiscussionThe findings provide some of the first evidence of PFAS exposure shaping a key measure of placental vascular function, which may underlie the impact of PFAS on perinatal and child health risks.