Prenatal exposure to mixtures of phthalates and bisphenol A and eczema risk: findings in atopic and non-atopic children from the LiNA birth cohort

Abstract

Background: We investigated whether maternal exposure to phthalate and bisphenol A (BPA) mixtures is associated with eczema in children, as most studies have only addressed single chemical exposures.

Methods: Nine phthalate metabolites and BPA were quantified in urine at gestational weeks 34-36 (n = 540) and total, inhalant, and food allergen-specific immunoglobulin (Ig)E levels (sx1, and fx5) were measured in serum from 4-year-old children of the LiNA cohort (n = 219). The association of prenatal exposure to phthalates and BPA, both single and mixed, with eczema and IgE was assessed in children stratified by atopy status. Three independent statistical models adjusted for covariates were used: logistic regression -also in the sex-stratified analysis-, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR). Moreover, an in silico toxicogenomic analysis was conducted to explore putative underlying mechanisms.

Results: The adjusted logistic regression showed that monobenzyl phthalate (MBzP; OR = 2.64, 95 % CI: 1.29-6.4) and the sum of di-2-ethylhexyl phthalate metabolites (2.09, 1.1-4.32) were significantly associated with eczema exclusively in atopic boys. The BKMR suggested a positive trend between chemical exposure and IgE values in the atopic subgroup. In the WQS model, the mixture' positive effect on eczema among atopic children was significant (1.90, 1.80-2.01) with MBzP (65.9 %), monoethyl phthalate (13.3 %), and BPA (10.9 %) being the main contributors, which jointly modulate antibody-mediated immunity and inflammation gene pathways in the toxicogenomic profiling.

Conclusions: Maternal exposure to mixtures of phthalates and BPA differentially impacts eczema risk among atopy-stratified children. The in silico chemical-gene interaction analysis in atopic children identified genes involved in immune cell activation and Ig production. Compared to non-atopic children, individual phthalates were significantly associated with eczema in atopic boys, suggesting that chemicals may have a larger effect size in predisposed populations.

Keywords: Atopic eczema; Bayesian kernel machine regression (BKMR); Bisphenol A; Immunoglobulin E (IgE); Weighted quantile sum (WQS) regression; phthalates.