Individual and combined association between nutritional trace metals and the risk of preterm birth in a recurrent pregnancy loss cohort

Abstract

BackgroundRecurrent pregnancy loss (RPL) was associated with an elevated risk of pregnancy complications, particularly preterm birth (PTB). However, the risk factors associated with PTB in RPL remained unclear. Emerging evidence indicated that maternal exposure to metals played a crucial role in the development of PTB. The objective of our study was to investigate the individual and combined associations of nutritional trace metals (NTMs) during pregnancy with PTB in RPL.MethodsUsing data from a recurrent pregnancy loss cohort (n = 459), propensity score matching (1:3) was performed to control for covariates. Multiple logistic regression and multiple linear regression were employed to identify the individual effects, while elastic-net regularization (ENET) and Bayesian kernel machine regression (BKMR) were used to examine the combined effects on PTB in RPL.ResultsThe logistic regression model found that maternal exposure to copper (Cu) (quantile 4 [Q4] vs. quantile 1 [Q1], odds ratio [OR]: 0.21, 95% confidence interval [CI]: 0.05, 0.74) and zinc (Zn) (Q4 vs. Q1, OR: 0.19, 95%CI: 0.04, 0.77) was inversely associated with total PTB risk. We further constructed environmental risk scores (ERSs) using principal components and interaction terms derived from the ENET model to predict PTB accurately (p < 0.001). In the BKMR model, we confirmed that Cu was the most significant component (PIP = 0.85). When other metals were fixed at the 25th and 50th percentiles, Cu was inversely associated with PTB. In addition, we demonstrated the non-linear relationships of Zn with PTB and the potential interaction between Cu and other metals, including Zn, Ca, and Fe.ConclusionIn conclusion, our study highlighted the significance of maternal exposure to NTMs in RPL and its association with PTB risk. Cu and Zn were inversely associated with PTB risk, with Cu identified as a crucial factor. Potential interactions between Cu and other metals (Zn, Ca, and Fe) further contributed to the understanding of PTB etiology in RPL. These findings suggest opportunities for personalized care and preventive interventions to optimize maternal and infant health outcomes.