Association of Co-Exposure to Polycyclic Aromatic Hydrocarbons and Metal(loid)s with the Risk of Neural Tube Defects:A Case-Control Study in Northern China

Objective Exposure to polycyclic aromatic hydrocarbons（PAHs） or metal（loid）s individually has been associated with neural tube defects（NTDs）.However,the impacts of PAH and metal（loid） co-exposure and potential interaction effects on NTD risk remain unclear.We conducted a case-control study in China among population with a high prevalence of NTDs to investigate the combined effects of PAH and metal（loid） exposures on the risk of NTD.Methods Cases included 80 women who gave birth to offspring with NTDs,whereas controls were 50women who delivered infants with no congenital malformations.We analyzed the levels of placental PAHs using gas chromatography and mass spectrometry,PAH-DNA adducts with 32P-post-labeling method,and metal（loid）s with an inductively coupled plasma mass spectrometer.Unconditional logistic regression was employed to estimate the associations between individual exposures and NTDs.Least absolute shrinkage and selection operator（LASSO） penalized regression models were used to select a subset of exposures,while additive interaction models were used to identify interaction effects.Results In the single-exposure models,we found that eight PAHs,PAH-DNA adducts,and 28 metal（loid）s were associated with NTDs.Pyrene,selenium,molybdenum,cadmium,uranium,and rubidium were selected through LASSO regression and were statistically associated with NTDs in the multiple-exposure models.Women with high levels of pyrene and molybdenum or pyrene and selenium exhibited significantly increased risk of having offspring with NTDs,indicating that these combinations may have synergistic effects on the risk of NTDs.Conclusion Our findings suggest that individual PAHs and metal（loid）s,as well as their interactions,may be associated with the risk of NTDs,which warrants further investigation.