Urinary Phthalate Metabolites and Biomarkers of Oxidative Stress in a Mexican-American Cohort: Variability in Early and Late Pregnancy

Abstract

People are exposed to phthalates through their wide use as plasticizers and in personal care products. Many phthalates are endocrine disruptors and have been associated with adverse health outcomes. However, knowledge gaps exist in understanding the molecular mechanisms associated with the effects of exposure in early and late pregnancy. In this study, we examined the relationship of eleven urinary phthalate metabolites with isoprostane, an established marker of oxidative stress, among pregnant Mexican-American women from an agricultural cohort. Isoprostane levels were on average 20% higher at 26 weeks than at 13 weeks of pregnancy. Urinary phthalate metabolite concentrations suggested relatively consistent phthalate exposures over pregnancy. The relationship between phthalate metabolite concentrations and isoprostane levels was significant for the sum of di-2-ethylhexyl phthalate and the sum of high molecular weight metabolites with the exception of monobenzyl phthalate, which was not associated with oxidative stress at either time point. In contrast, low molecular weight metabolite concentrations were not associated with isoprostane at 13 weeks, but this relationship became stronger later in pregnancy (p-value = 0.009 for the sum of low molecular weight metabolites). Our findings suggest that prenatal exposure to phthalates may influence oxidative stress, which is consistent with their relationship with obesity and other adverse health outcomes.

Keywords: birth cohort; endocrine disruptors; in utero exposure; isoprostane; oxidative stress; phthalates; pregnancy.

Figure 1

Differences in the phthalate metabolite concentrations (creatinine adjusted) between samples from the same individual collected at 13 and 26 weeks gestation. Differences that are statistically significant are indicated by: * p < 0.05, ** p < 0.01 and *** p < 0.001.

Figure 2

Correlation matrix of concentrations between eleven phthalate metabolites and isoprostane averaged for two time points in early and late pregnancy. Each colored square represents Pearson’s correlation coefficient between different phthalate metabolites. The dark blue squares indicate strong positive correlations with correlation coefficients ranging from 0.5–1.

Figure 3

Heatmap of the relationship between phthalate metabolite concentrations and demographic variables at (a) 13 and (b) 26 weeks gestation. Each colored square represents the −log10 p-value for the association of demographic variables (using the same categories as Table 1) with phthalate metabolites concentrations as determined by analysis of variance (ANOVA). The darker squares represent associations with smaller p-values, with dark red representing the most significant associations (p ~ 1 × 10⁻⁴). Each model is adjusted for creatinine by including it as a covariate.