RESEARCH ARTICLE Associations between Maternal Biomarkers of Phthalate Exposure and Inflammation Using Repeated Measurements across Pregnancy

Phthalate exposure is prevalent in populations worldwide, including pregnant women. Maternal urinary metabolite concentrations have been associated with adverse reproduc-tive outcomes, but underlying mechanisms remain unclear. Here we investigate inflamma-tion as a possible pathway by examining phthalates in association with inflammation biomarkers, including C-reactive protein (CRP) and a panel of cytokines (IL-1β, IL-6, IL-10, and TNF-α) in a repeated measures analysis of pregnant women (N = 480). Urinary phthal-ate metabolites and plasma inflammation biomarkers were measured from samples col-lected at up to four visits per subject during gestation (median 10, 18, 26, and 35 weeks). Associations were examined using mixed models to account for within-individual correlation of measures. Few statistically significant associations or clear trends were observed, although in full models mono-carboxypropyl phthalate (MCPP) was significantly (percent change with interquartile range increase in exposure [%Δ] = 8.89, 95 % confidence interval [CI] = 3.28, 14.8), and mono-benzyl phthalate (MBzP) was suggestively (%Δ = 6.79, 95%CI =-1.21, 15.4) associated with IL-6. Overall these findings show little evidence of an associa-tion between phthalate exposure and peripheral inflammation in pregnant women. To inves-tigate inflammation as a mechanism of phthalate effects in humans, biomarkers from target tissues or fluids, though difficult to measure in large-scale studies, may be necessary to detect effects