Phthalates, Bisphenols, and Childhood Allergic Phenotypes: Findings from Two Birth Cohort Studies

ABSTRACT Background Phthalates and bisphenols may contribute to childhood allergic outcomes, but whether these are differentially associated with atopic or non-atopic phenotypes is uncertain. We investigated whether early-life exposure to these chemicals differentially impacts atopic and non-atopic allergic outcomes. Methods We used two prospective birth cohorts to investigate distinct exposure windows. The Barwon Infant Study (n = 797) measured urinary phthalate and bisphenol metabolites at 36 weeks’ gestation. The Canadian Healthy Infant Longitudinal Development Study (n = 993) measured phthalate metabolites at 3, 12, and 36 months. Atopy was assessed via skin prick tests at 4-5 years. Outcomes included asthma, wheeze, eczema, and rhinitis at 4-5 years. Models were stratified by atopy. We modelled exposure mixtures using quantile G-computation and Bayesian kernel machine regression. Results Phthalate mixtures were associated with increased asthma risk in both exposure windows. Prenatal phthalate mixtures were more strongly associated with non-atopic asthma (adjusted risk ratio [aRR] = 1.83; 95% confidence interval [CI]: 1.10-3.04), with evidence of effect modification by atopy (p = 0.02 for interaction). Postnatal phthalate mixtures were associated with non-atopic asthma (aRR = 1.82, 95% CI: 1.19-2.78), though the association did not differ by phenotype (p = 0.45 for interaction). Phthalate mixtures showed U-shaped (prenatal) and inverse U-shaped (postnatal) associations with atopic asthma, and linear associations with non-atopic asthma. There was little evidence of associations for other allergic outcomes. Conclusion Early-life exposure to phthalates may differentially influence the risk of childhood atopic and non-atopic asthma. Future studies are needed to confirm these associations. HIGHLIGHTS We used two birth cohorts to examine distinct exposure windows to phthalates. Pre-and postnatal phthalate exposure was associated with increased asthma risk. Pre-and postnatal associations with asthma differed by atopic status. There was little evidence of association with other allergic outcomes.