Phthalates, bisphenols, and childhood allergic Phenotypes: Findings from two birth cohort studies

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. We used two birth cohorts to investigate late pregnancy and early childhood exposure windows. The Barwon Infant Study (n = 797) in Australia 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 using 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. Prenatal mono-carboxy-propyl phthalate was suggestively associated with non-atopic asthma (adjusted risk ratio [aRR] = 1.12; 95 % confidence interval [CI]: 0.99–1.27) with evidence of effect modification by atopy (p for interaction = 0.02). Prenatal bisphenol A was inversely associated with overall wheeze (aRR = 0.64; 95 % CI: 0.44–0.94). In the postnatal period, diethyl and dibutyl phthalates were associated with non-atopic asthma, but not with atopic asthma, though estimates did not differ substantially by atopic status. Prenatal phthalate mixtures were more strongly associated with non-atopic asthma (aRR = 1.83; 95 % 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), but not atopic asthma, though the association did not differ by phenotype (p for interaction = 0.45). Phthalate mixtures showed U-shaped (prenatal) and inverse U-shaped (postnatal) associations with atopic asthma, and linear positive associations with non-atopic asthma. There was little evidence of associations for other allergic outcomes. Early-life exposure to phthalates may differentially influence the risk of childhood atopic and non-atopic asthma.