Association of placental single and mixed metal burdens with offspring dyslipidemia: Can vitamin D levels during pregnancy alleviate this effect?

Metals can partly accumulate in the placenta and disrupt placental function, thereby affecting fetal programming. Prenatal metal exposure may be associated with long-term lipid health in offspring, but this association has not been studied in birth cohorts. In the Ma'anshan birth Cohort (MABC), placental tissue concentrations of fourteen metals were quantified. We assessed the lipid profile of children aged 5-6 years and identified children with dyslipidemia. Placental thallium (Tl) (OR = 1.555; 95 % CI: 1.150-2.103), vanadium (V) (OR = 1.465; 95 % CI: 1.131-1.898), and molybdenum (Mo) (OR = 1.446; 95 % CI: 1.038-2.014) are associated with increased risk of dyslipidemia in children. Both bayesian kernel machine regression (BKMR) and weighted quantile sum (WQS) models suggested that placental metal mixture were positively associated with increased risk of dyslipidemia. The results of both WQS and quantile g-computation (Qgcomp) analyses revealed that Mo, V, and Tl were the three key metals predominantly responsible for the heightened risk of dyslipidemia. In the interaction analysis, no significant moderating effect on dyslipidemia was found between maternal average vitamin D levels during pregnancy and single or mixed placental metals. However, the association between placental V and dyslipidemia was more pronounced in maternal average vitamin D deficiency group, while placental Mo was associated with dyslipidemia only in maternal average vitamin D non-deficiency group. Moreover, the association of placental Tl, V, Mo, Zn, Cu with dyslipidemia was particularly prominent in mother-child pairs with metabolic disorders during pregnancy. In summary, placental exposure to Tl, V and Mo may increase the risk of dyslipidemia in offspring, no significant evidence of a modifying effect by average vitamin D levels. While exploratory trimester-specific analyses suggest potential complexity, these findings require confirmation in future studies to avoid conflicting conclusions.