Urinary paraben derivatives in pregnant women at three trimesters: Variability, predictors, and association with oxidative stress biomarkers

Exposure to parabens has been shown to increase oxidative stress, which has a vital impact on the development of numerous diseases. However, few studies reported the effects of the paraben derivatives on oxidative stress, particularly among pregnant women. This study, using repeated measurements, aimed to understand the exposure profiles of urinary paraben derivative concentrations and their relationships with oxidative stress biomarkers (OSBs). A total of 861 pregnant women, who provided spot urine samples at three trimesters, were included, and 2583 urine samples were used to measure four paraben derivatives [p-hydroxybenzoic acid (p-HB), 3,4-dihydroxybenzoic acid (3,4-DHB), methyl protocatechuate, and ethyl protocatechuate], four parabens (methyl, ethyl, propyl, and butyl), and three OSBs [8-hydroxy-2'-deoxyguanosine (for DNA), 8-hydroxyguanosine (for RNA), and 4-hydroxy nonenal mercapturic acid (for lipid)]. Pregnant women were extensively exposed to parabens and paraben derivatives with detection frequencies (DFs) of 86.1%-100%, except for butylparaben with a DF of 14.9%. p-HB and 3,4-DHB had relatively high urinary concentrations (specific gravity-adjusted median values: 1394 and 74.5 ng/mL, respectively). Low reproducibility in paraben derivatives was found across the three trimesters. Sampling season, pre-pregnancy body mass index, and infant sex were predictors of some paraben derivatives/parabens. Linear mixed model analyses showed that all target compounds (if DF > 50%) were associated with increases in all the selected OSBs, where the percent change in OSBs with an interquartile range increase in paraben concentration ranged from 9.85% to 24.7%, while those in paraben derivative concentration ranged from 13.8% to 72.1%. Weighted quantile sum model showed that joint exposure was significantly associated with increased OSBs, and paraben derivatives were stronger contributors to OSBs compared with parabens. Overall, urinary paraben derivatives were associated with increased oxidative stress of nucleic acids and lipid in pregnant women.