Prenatal Exposure to Mixtures of Nonpersistent Endocrine-Disrupting Chemicals and Angiogenic Biomarkers, Placental Function, and Fetal Growth

Exposure to endocrine-disrupting chemicals (EDCs) during pregnancy may influence the placenta and fetal growth; however, evidence is scarce regarding EDC mixtures, newer chemicals, and the role of angiogenic biomarkers and fetoplacental hemodynamics. We aimed to examine the associations between nonpersistent EDC mixtures and fetal growth, fetoplacental hemodynamics, and angiogenic biomarkers. We included 734 pregnant participants from the Barcelona Life Study Cohort (BiSC), Spain (2018-2021). Metabolites of phthalates, DINCH, insecticides, polycyclic aromatic hydrocarbons, pesticides, flame retardants, and parent compounds of phenols and parabens were measured in pools of week-long maternal urine samples at 18 and 34 weeks' gestation. Penalized LASSO-type multigroup Bayesian Weighted Quantile Sum Regression estimated associations with fetal growth, fetoplacental hemodynamics, and angiogenic biomarkers. Birthweight z-score decreased with low-molecular-weight phthalate (LMWP) (β = -0.119; CrI -0.224, -0.008) mixtures and increased with organophosphate mixtures (β = 0.143; CrI 0.042, 0.245). LMWP exposure was also associated with altered hemodynamics and angiogenic biomarkers; angiogenic biomarkers mediated the relationship with birthweight z-score (ACME = -0.032; 95% CI -0.062, -0.009; p = 0.002). This comprehensive study suggests that mixtures of low-molecular-weight phthalates and organophosphate compounds may alter fetal growth and that angiogenic biomarkers may play a role as mediator.