Prenatal exposure to phthalates and phthalate replacements in relation to chorionic plate surface vasculature at...

Pregnant people are ubiquitously exposed to endocrine-disrupting phthalates through consumer products and food. The placenta may be particularly vulnerable to the adverse effects of phthalates, with evidence from animal models suggesting impacts on placental development and vascularization. We translate this research to humans, examining gestational exposure to phthalates and phthalate replacements in relation to novel markers of chorionic plate surface vascularization. Phthalate and phthalate replacement metabolites were measured in first trimester urine from pregnant participants in the Understanding Pregnancy Signals and Infant Development (UPSIDE) cohort (n = 154). At delivery, placentae underwent specialized 2D and 3D digital imaging to quantify chorionic plate surface vasculature. Using weighted quantile g-computation mixtures methods as well as multivariable linear regression models examining individual metabolites, we evaluated associations with overall chorionic plate surface area and five chorionic plate surface vascular measures, adjusting for covariates. We additionally examined interactions with placental sex. Exposure to a phthalate mixture was associated with longer total arterial arc length (β = 9.64 cm; 95%CI: 1.68, 17.59), shorter mean arterial arc length (β = -0.07 cm; 95%CI: -0.14, -0.01), and more arterial branch points (β = 5.77; 95%CI: 1.56, 9.98), but not chorionic plate surface area. In models considering individual metabolites and their molar sums, results were strongest for the metabolites of Di-isobutyl phthalate (DiBP), Di-isononyl phthalate (DiNP), and Di(2-ethylhexyl) phthalate (DEHP). Associations with metabolites of phthalate replacements tended to be in the same direction but weaker. Few sex differences were observed. Gestational phthalate exposure may be associated with alterations in placental chorionic plate surface vasculature characterized by more branching and shorter segments. These alterations may have implications for placental perfusion and suggest a placental mechanism by which phthalates may impact fetal development.