Associations Between Prenatal Phthalate Exposure and Atopic Symptoms in Childhood: Effect Modification by Child Sex

Background: The global rise in atopic diseases, like atopic dermatitis and allergic rhinitis, may be linked to prenatal exposure to endocrine-disrupting chemicals like phthalates, with potential sex-specific effects. Methods: We analyzed 558 mother–child pairs from the PROGRESS birth cohort in Mexico City. Maternal urinary phthalate metabolites were measured during the 2nd and 3rd trimesters. Atopic dermatitis and allergic rhinitis symptoms were assessed at ages 4–6 and 6–8 years using the International Study of Asthma and Allergies in Childhood survey. Weighted Quantile Sum Regression (WQS) was used to assess sex-specific mixture associations. Individual sex-specific phthalate associations were examined using modified Poisson models with inclusion of product terms and stratification. Models were adjusted for maternal age, education, parity, pre-pregnancy body mass index, and prenatal tobacco exposure. Results: We found that child sex modified associations between the 2nd trimester phthalate mixture and current atopic dermatitis symptoms at both 4–6 years (WQS*sex OR: 1.23, 95% CI: 1.00–1.60) and 6–8 years (WQS*sex OR: 1.46, 95% CI: 1.01–2.10). Among males, higher phthalate concentrations were positively associated with symptoms at both ages (OR: 1.10, 95% CI: 0.92, 1.32; OR: 1.16, 95% CI: 0.92, 1.46), while associations were negative in females (OR: 0.87, 95% CI: 0.73, 1.04; OR: 0.79, 95% CI: 0.62, 1.02). No sex-specific associations were found for 3rd trimester exposures. Individual metabolite analyses also showed effect modification by sex for 2nd trimester exposures. Conclusions: Prenatal exposure to phthalates is associated with atopic dermatitis symptoms in childhood in a sex-specific manner.