In Utero Exposure to Select Phenols and Phthalates and Respiratory Health in Five-Year-Old Boys: A Prospective Study

Abstract

Background: Phenols and phthalates may have immunomodulatory and proinflammatory effects and thereby adversely affect respiratory health.

Objective: We estimated the associations between gestational exposure to select phthalates and phenols and respiratory health in boys.

Methods: Among 587 pregnant women from the EDEN (Etude des Déterminants pré et post natals du développement et de la santé de l'Enfant) cohort who delivered a boy, 9 phenols and 11 phthalates metabolites were quantified in spot pregnancy urine samples. Respiratory outcomes were followed up by questionnaires until age 5, when forced expiratory volume in 1 s (FEV1) was measured by spirometry. Adjusted associations of urinary metabolites log-transformed concentrations with respiratory outcomes and FEV1 in percent predicted (FEV1%) were estimated by survival and linear regression models, respectively.

Results: No phenol or phthalate metabolite exhibited clear deleterious associations simultaneously with several respiratory outcomes. Ethyl-paraben was associated with increased asthma rate [hazard rate (HR)=1.10; 95% confidence interval (CI): 1.00, 1.21] and tended to be negatively associated with FEV1% (beta=-0.59; 95% CI: -1.24, 0.05); bisphenol A tended to be associated with increased rates of asthma diagnosis (HR=1.23; 95% CI: 0.97, 1.55) and bronchiolitis/bronchitis (HR=1.13; 95% CI: 0.99, 1.30). Isolated trends for deleterious associations were also observed between 2,5-dichlorophenol and wheezing, and between monocarboxynonyl phthalate, a metabolite of di-isodecyl phthalate (DIDP), and wheezing.

Conclusion: Ethyl-paraben, bisphenol A, 2,5-dichlorophenol, and DIDP tended to be associated with altered respiratory health, with ethyl-paraben and bisphenol A exhibiting some consistency across respiratory outcomes. The trends between bisphenol A pregnancy level and increased asthma and bronchiolitis/bronchitis rates in childhood were consistent with a previous cohort study. https://doi.org/10.1289/EHP1015.

Figure 1.

Adjusted associations of (A) phenols and (B) phthalates metabolites ln-transformed standardized concentrations with respiratory outcomes (HR, $\mathit{n}=587$) and ${\text{FEV}}_1\%$ in boys (beta, $\mathit{n}=228$, EDEN cohort). Effect estimates for 1-unit increase in ln-transformed standardized concentrations. Adjusted for center, residence area, parental history of asthma/allergies, maternal ethnicity, maximal parental education level, passive or active smoking during pregnancy, postnatal passive smoking, older siblings, child care (and additionally adjusted for boy’s height and age in spirometry analysis). Multiple imputation was used to handle missing values in covariates (100 imputations were performed). Phenols and phthalates metabolites concentrations were standardized for urine sampling conditions (see Methods section). Diamond and triangle markers represent HR and beta values, respectively, with error bars for 95% CI.