Prenatal exposure to phthalate mixtures and child neurodevelopment in toddlers aged 1-3 years from the PROTECT birth cohort.

Phthalates are widely used plasticizers and solvents in a variety of consumer and personal care products, resulting in ubiquitous exposure across the general population. Pregnancy represents a particularly critical window of vulnerability, as prenatal phthalate exposures have been linked to adverse health outcomes, including preterm birth and child developmental problems. While growing evidence highlights potential neurotoxic effects in children, few studies have examined the combined impact of multiple phthalates and newly introduced replacement chemicals. In this study, we included 199 mother-child dyads from the PROTECT birth cohort in Puerto Rico. We assessed prenatal exposure to multiple phthalates and a replacement chemical, di(2-ethylhexyl) terephthalate (DEHTP), by measuring biomarkers in maternal urine samples. Neurodevelopmental outcomes were then evaluated in early childhood (ages 1-3 years) across multiple domains - adaptive, cognitive, communication, motor, and personal-social. We employed a range of mixture modeling approaches-adaptive elastic net (adENET), Bayesian kernel machine regression (BKMR), and quantile g-computation (Q-gcomp). We identified mono(carboxyisononyl) phthalate (MCOP) as a key contributor to poorer neurodevelopmental outcomes and observed an overall adverse trend for the combined mixture. These results provide evidence of additive and mixture effects among multiple phthalates and replacement chemicals, underscoring the need for further research to elucidate the biological mechanisms by which these exposures may collectively influence child neurodevelopment.