Correlation between mixed exposure to several heavy metals during early pregnancy and fetal low birth weight: Possible mediating effect of mitochondrial DNA copy number.

BACKGROUND

Epidemiological investigations regarding the correlation between mixed heavy metals (HMs) exposure in early pregnancy and low birth weight (LBW) have shown contradictory findings. Moreover, investigations into the fundamental mechanisms, including the possible impacts of HMs exposure on mitochondrial DNA copy number (mtDNAcn), are limited.

OBJECTIVES

This study sought to examine the influence of mixed HMs exposure during early gestation on the prevalence of LBW and to ascertain whether mtDNAcn mediates this relationship.

METHODS

The Second Affiliated Hospital of Guilin Medical University conducted a nested case-control study involving 49 pregnant women who delivered LBW infants and 196 matched controls. Urine and blood samples were collected during early pregnancy, along with placental and umbilical cord blood samples at delivery. Concentrations of ten metals-magnesium(Mg), manganese(Mn), copper(Cu), arsenic(As), selenium(Se), strontium(Sr), molybdenum(Mo), cadmium(Cd), thallium(Tl), and lead(Pb)-were quantified. mtDNAcn was measured using real-time quantitative polymerase chain reaction (qPCR). Random forest analysis identified five metals-As, Se, Tl, Mn and Cd -as most strongly associated with the risk of preterm birth in LBW cases. These were selected for further analysis. Conditional logistic regression was applied to examine associations between early maternal urinary metal levels and infant malformations. To assess the combined effect of these metals on LBW, weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) were used. Finally, mediation analysis was conducted to explore whether mtDNAcn mediated the relationship between Mn exposure and LBW.

RESULTS

The results of the study revealed a significant association between urinary Mn concentrations and LBW, with a p-value of0.015 and an odds ratio (OR) of 2.33 (95%CI:1.18-4.58) before adjusting for confounders. After adjusting for confounders, urinary manganese concentration remained significantly associated with LBW (p=0.017), with an OR of 2.36(95%CI:1.16-4.80). The odds of LBW significantly increased as exposure levels moved from the 25th to the 75th percentile for metal combinations, with the effect becoming more pronounced when the exposure index exceeded the 60th percentile. Notably, mtDNAcn levels mediated 27%of the association between Mn exposure and the incidence of umbilical cord bypass syndrome.

CONCLUSION

In conclusion, our data suggest that changes in mtDNAcn may mediate the association between Mn exposure during early pregnancy and the development of LBW. This study not only provides new evidence of the relationship between HMs exposure and fetal developmental disorders in China, but also serves as a valuable reference for global awareness regarding the effects of environmental pollution during pregnancy on fetal health.