Prenatal exposure to solvents and fetal outcomes in a Canadian pregnancy cohort

The solvents N-methyl-2-pyrrolidone (NMP) and N-ethyl-2-pyrrolidone (NEP) are established developmental toxicants; however, epidemiological data are lacking. We quantified associations between urinary NEP and NMP metabolites concentrations and pregnancy outcomes in participants enrolled in the pan-Canadian Maternal-Infant Research on Environmental Chemicals study (n = 1865) (2008-2011). Using discrete time survival analysis and logistic regression, we calculated the odds of preterm birth (PTB) and fetal loss. We used multivariable linear regression to quantify associations between metabolites and birth weight z-scores. Participants with quantifiable concentrations of the NEP metabolite 5-hydroxy-N-ethyl-2-pyrrolidone (5-HNEP) had a 41% increased odds of PTB (95% CI: 0.92-2.17). An interquartile range increase in concentrations of the NMP metabolite 5-hydroxy-N-methyl-2-pyrrolidone (5-HNMP) was associated with a reduced odds of fetal loss (OR = 0.51 95% CI: 0.30,0.89). All other effect estimates were centered around the null value. We report widespread, low-level exposure to NMP metabolites yet no evidence of adverse effects on fetal health. Our analysis of fetal loss was most likely subject to selection bias resulting from conditioning on pregnancies with available first trimester urine samples Our finding that 5-HNEP exposure may increase risk of preterm birth provides impetus for further biomonitoring and etiological research in a pregnant population with contemporary NEP exposure.