Evaluating the association between exposure to multiple metals and adverse pregnancy outcomes based on a multi-step...

Adverse pregnancy outcomes (APOs) pose a serious threat to the safety of both the mother and the fetus. The association between metal exposure during pregnancy and the risk of APOs remains inconsistent. Therefore, this study aimed to evaluate the association between exposure to multiple metals and the risk of APOs based on a multi-step statistical analysis strategy.

A birth cohort study including 707 pregnant women was performed in the present study, and 182 women were ultimately diagnosed with APOs. Blood levels of arsenic (As), cadmium (Cd), mercury (Hg), lead (Pb), barium (Ba), cobalt (Co), chromium (Cr), manganese (Mn), molybdenum (Mo), nickel (Ni), thallium (Tl), and vanadium (V) were measured in pregnant women. Multi-step statistical analyses were conducted to evaluate the associations between metals exposure and APO risk. First, cluster and scatter clustering analyses were used to assess the overlap for high exposure levels of metals among participants. Second, binary logistic regression was performed to assess the association between each single metal level and APO risk, respectively. Third, weighted quantile sum (WQS) regression and quantile-based g-computation (QGC) were conducted to identify the key metals contributing most to APO risk. Finally, Bayesian kernel machine regression (BKMR) evaluated the joint effects of these key metals on APO risk.

The results from cluster analyses revealed that there were substantial overlaps for high exposure levels of metals among pregnant women. Higher blood levels of Ba and Tl were associated with an increased APO risk (Ba: adjusted odds ratio [aOR] = 2.03, 95 % confidence interval [CI]: 1.33-3.10; Tl: aOR = 1.73, 95 % CI: 1.13-2.63). Consistently, results from the WQS regression model suggested that Ba (0.27), Tl (0.16), Pb (0.01) and V (0.01) were major contributors to APO risk (p < 0.05), which was further supported by the results from QGC regression model. The BKMR model indicated that the mixtures of Ba, Tl, Pb and V, identified through the WQS and QGC models, were positively associated with the risk of APOs.

In this study, we observed substantial overlaps in high exposure levels of metals among pregnant women. Ba, Tl, Pb, and V were identified as the major contributors to the risk of APOs. Co-exposure to these metals was linked to an increased risk of APOs. This highlights the importance of avoiding metal exposure during pregnancy to protect maternal and fetal health.