Prospective Associations of Early Pregnancy Metal Mixtures with Mitochondria DNA Copy Number and Telomere Length in Maternal and Cord Blood

BACKGROUND: Metal exposure during pregnancy influences maternal and child health. Oxidative stress and inflammation may mediate adverse effects of heavy metals, whereas essential metals may act as antioxidants. Mitochondrial DNA is a prime target for metal-induced oxidative damage. Telomere dysfunction is attributed to imbalances between reactive oxidant species and antioxidants. OBJECTIVES: We evaluated individual and joint associations of prenatal metals with mitochondrial DNA copy number (mtDNAcn) and telomere length (TL) in maternal and cord blood as biomarkers of inflammation and oxidative stress. METHODS: We measured six nonessential metals (arsenic, barium, cadmium, cesium, lead, mercury) and four essential metals (magnesium, manganese, selenium, zinc) in first-trimester maternal red blood cells in Project Viva, a U.S. prebirth cohort. We measured relative mtDNAcn ([Formula: see text]) and TL ([Formula: see text]) in second-trimester maternal blood and mtDNAcn ([Formula: see text]) and TL ([Formula: see text]) in cord blood. We used multivariable linear regression and quantile g-computation to estimate associations between prenatal metals and the biomarkers. We used generalized additive models and Bayesian kernel machine regression to examine nonlinearity and interactions. RESULTS: A 2-fold increase in maternal magnesium was associated with lower maternal [[Formula: see text] , 95% confidence interval (CI): [Formula: see text] , [Formula: see text]] and cord blood ([Formula: see text] , 95% CI: [Formula: see text] , [Formula: see text]) mtDNAcn. Lead was associated with higher maternal mtDNAcn ([Formula: see text] , 95% CI: 0.01, 0.06). Selenium was associated with longer cord blood TL ([Formula: see text] , 95% CI: 0.01 0.50). An association was observed between the nonessential metal mixture and higher maternal mtDNAcn ([Formula: see text] , 95% CI: 0.01, 0.07). There was a nonlinear relationship between cord blood mtDNAcn and magnesium; maternal mtDNAcn and barium, lead, and mercury; and maternal TL and barium. DISCUSSION: Maternal exposure to metals such as lead, magnesium, and selenium was associated with mtDNAcn and TL in maternal second trimester and cord blood. Future work will evaluate whether these biomarkers are associated with child health. https://doi.org/10.1289/EHP9294