The Relationship Between Heavy Metals and Missed Abortion: Using Mediation of Serum Hormones.

Abstract

Accumulating evidence suggests that heavy metal exposure may have adverse effects on the fetal development. Furthermore, disruption of serum hormone homeostasis can result in the adverse pregnancy outcomes. Therefore, this study aimed to investigate the potential association between heavy metals and missed abortion, with a focus on whether serum hormones mediate this relationship. The concentrations of heavy metals and hormones in serum were measured in this case-control study. Statistical models including, logistic regression model, principal component analysis (PCA), and weighted quantile sum (WQS) regression model were employed to examine the relationship between heavy metals, serum hormones, and missed abortion. Furthermore, the mediation analysis was performed to assess the role of serum hormones as potential mediators in this relationship. This study revealed significant associations between heavy metal exposure and missed abortion. Notable, the WQS index weight, which was mainly influenced by copper (Cu) and zine (Zn), is associated with missed abortion. Moreover, heavy metals including manganese (Mn), nickel (Ni), Zn, arsenic (As), Cu, cadmium (Cd), and lead (Pb) were found to be associated with serum levels of β-human chorionic gonadotropin (β-hCG), progesterone (P), estradiol (E2), and lactogen (HPL). In addition, the mediation analysis indicated that β-hCG explained a portion of the association (ranging from 18.77 to 43.51%) of between Mn, Ni, Zn, and As exposure and missed abortion. Serum P levels explained 17.93 to 51.70% of the association between Ni, Cu, and As exposure and missed abortion. Serum E2 levels played a significant mediating role, explaining a portion of the association (ranging from 22.14 to 73.60%) between Mn, Ni, Cu, As, Cd, and Pb exposure and missed abortion. Our results suggested that β-hCG, P, and E2 are one of the potential mediators in the complex relationship between heavy metals exposure and missed abortion. These results highlight the importance of considering both heavy metal exposure and serum hormone levels in understanding the etiology of missed abortion.