Urinary metabolites of multiple volatile organic compounds among pregnant women across pregnancy: Variability, exposure characteristics, and associations with selected oxidative stress biomarkers

Volatile organic compounds (VOCs) are a group of pollutants pervasive in daily life with identified adverse health effects. However, no study has investigated the variability in VOC metabolites during pregnancy and their relationships with oxidative stress biomarkers in pregnant women. In the present study, the variability of 21 selected VOC metabolites was examined and their relationships with three selected oxidative stress biomarkers measured in spot urine samples at three trimesters of 1094 pregnant women were analyzed. Nineteen VOC metabolites were ubiquitous in the urine samples with detection rates ranging from 75.9% to 100%. Mono-hydroxybutenyl mercapturic acid (MHBMA) and s-phenyl mercapturic acid (PMA) had detection rates lower than 1.00%. Intraclass correlation coefficients (ICCs) of the detected analytes at three trimesters ranged 0.07-0.24, and the concentrations were highest in the first trimester. Higher concentrations of some VOC metabolites were related with participant characteristics including higher pre-pregnancy body mass index (BMI), lower education level, unemployment during pregnancy, multiparity, and sampling season of summer or winter. In repeated cross-sectional analyses, interquartile range (IQR) increases in the 19 detected VOC metabolites were positively related with 8-hydroxy-2 '-deoxyguanosine (8-OHdG), 8-hydroxyguanosine (8-OHG), and 4-hydroxy nonenal mercapturic acid (HNEMA) with the estimates ranging from 9.00% to 204%. The mixture effect of the VOC metabolites on the oxidative stress biomarkers was further assessed using weighted quantile sum regression (WQS) models and the results showed that the WQS index of VOC metabolite mixture was significantly asso-ciated with 8-OHdG (beta: 0.37, 0,32, and 0.39 at the 1st, 2nd, and 3rd trimester, respectively), 8-OHG (0.38, 0.32, and 0.39) and HNEMA (1.21, 1.08, and 1.10). Glycidamide mercapturic acid (GAMA), and trans,trans-muconic acid (MU) were the strongest contributors of the mixture effect on 8-OHdG, 8-OHG, and HNEMA, respectively. Overall, urinary concentrations of the VOC metabolites during pregnancy were strongly associated with the oxidative stress biomarkers.