Prenatal phthalate exposure and emotional-behavioral problems in children aged 1.5 to 3 years from the PROTECT birth cohort.

Dara Nall Watkins, Bhramar Mukherjee, Sung-Soo Park, Gredia Huerta Montañez, Zaira Y Rosario-Pabón, Carmen M Vélez-Vega, Joaquín G Cordero, Akram Alshawabkeh, John D Meeker

J Expo Sci Environ Epidemiol

Jun 2, 2026

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Abstract

BACKGROUND: Phthalates are synthetic chemicals commonly used in plastics and personal care products, resulting in widespread human exposure. As recognized endocrine disruptors, phthalates are of particular concern during pregnancy as pregnancy is a vulnerable period for both maternal and fetal health. Although prenatal phthalate exposure has been associated with child neurodevelopmental outcomes and emotional and behavioral problems (EBP), a crucial knowledge gap remains, particularly regarding emerging phthalate replacements and phthalate mixtures. OBJECTIVE: This study examined associations between prenatal exposure to phthalates and emerging phthalate replacements, both individually and as mixtures, and early childhood EBP. METHODS: We included 306 mother-child pairs from the PROTECT birth cohort in Puerto Rico. Phthalate metabolite concentrations were measured in maternal urine at approximately 18, 22, and 26 weeks' gestation. Early childhood EBP outcomes (Externalizing, Internalizing, and Total scores) were assessed when children were 1.5 to 3 years old. Negative binomial regression models were used to estimate associations between individual prenatally measured phthalate metabolites and EBP outcomes. Sensitivity analyses evaluated effect modification by child sex and timing of exposure. Mixture effects were investigated using adaptive elastic net for variable selection and quantile g-computation for combined effect estimation. RESULTS: Several specific phthalate metabolites (e.g., DEHP and DIBP metabolites) were associated with early childhood EBP symptoms in single-pollutant analyses. Sensitivity analyses by gestational timing identified additional associations, including for the replacement chemical, DEHTP, at approximately 26 weeks' gestation. In mixture analyses, a few metabolites were identified as key predictors, though the overall mixture effect was not statistically significant. SIGNIFICANCE: These findings suggest prenatal phthalate exposure may contribute to early childhood EBP, particularly at specific gestational windows. Further research addressing mixture effects and critical exposure periods is warranted. IMPACT: Identifying risk factors for early childhood EBP is crucial, given the rising global prevalence and the potential for early onset EBP to predict persistent mental health issues later in life. Our findings highlight the need to reduce prenatal phthalate exposure, a modifiable risk factor, with special attention to critical windows of susceptibility during pregnancy. Additionally, further research is warranted to elucidate the complex interactions among multiple phthalates, which may act through the same or different modes of action, to better understand their combined impact on early childhood EBP.