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

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Prospective Associations of Early Pregnancy Metal Mixtures with Mitochondria DNA Copy Number and Telomere Length in Maternal and Cord Blood
Environmental Health Perspectives ( IF 10.1 ) Pub Date : 2021-11-19 , DOI: 10.1289/ehp9294
Anna R Smith ₁ , Pi-I D Lin ₂ , Sheryl L Rifas-Shiman ₂ , Mohammad L Rahman ₂ , Diane R Gold _{3,

4} , Andrea A Baccarelli ₅ , Birgit Claus Henn ₆ , Chitra Amarasiriwardena ₇ , Robert O Wright ₇ , Brent Coull ₈ , Marie-France Hivert _{2,

9} , Emily Oken ₂ , Andres Cardenas ₁

Affiliation

Division of Environmental Health Sciences, School of Public Health and Center for Computational Biology, University of California, Berkeley, Berkeley, California, USA.
Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts, USA.
Department of Environmental Health, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts, USA.
Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston Massachusetts, USA.
Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, New York, USA.
Department of Environmental Health, Boston University School of Public Health, Boston University, Boston, Massachusetts, USA.
Department of Environmental Medicine and Institute for Exposomic Research, Icahn School of Medicine at Mount Sinai, New York City, New York, USA.
Department of Biostatistics, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts, USA.
Diabetes Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.

Abstract

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 ( $lowercase italic n equals 898$ ) and TL ( $lowercase italic n equals 893$ ) in second-trimester maternal blood and mtDNAcn ( $lowercase italic n equals 419$ ) and TL ( $lowercase italic n equals 408$ ) 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 [ $β = - 0.07$ , 95% confidence interval (CI): $negative 0.10$ , $negative 0.01$ ] and cord blood ( $β = - 0.08$ , 95% CI: $negative 0.20$ , $negative 0.01$ ) mtDNAcn. Lead was associated with higher maternal mtDNAcn ( $lowercase beta equals 0.04$ , 95% CI: 0.01, 0.06). Selenium was associated with longer cord blood TL ( $lowercase beta equals 0.30$ , 95% CI: 0.01 0.50). An association was observed between the nonessential metal mixture and higher maternal mtDNAcn ( $lowercase beta equals 0.04$ , 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

中文翻译：

早期妊娠金属混合物与母体和脐带血中线粒体 DNA 拷贝数和端粒长度的前瞻性关联

摘要

背景：

怀孕期间接触金属会影响母婴健康。氧化应激和炎症可能介导重金属的不利影响，而必需金属可能充当抗氧化剂。线粒体 DNA 是金属诱导的氧化损伤的主要目标。端粒功能障碍归因于活性氧化剂种类和抗氧化剂之间的不平衡。

目标：

我们评估了产前金属与母体和脐带血中线粒体 DNA 拷贝数 (mtDNAcn) 和端粒长度 (TL) 的个体和联合关联，作为炎症和氧化应激的生物标志物。

方法：

我们在美国产前队列 Project Viva 中测量了孕早期母体红细胞中的六种非必需金属（砷、钡、镉、铯、铅、汞）和四种必需金属（镁、锰、硒、锌）。我们测量了相对 mtDNAcn ( $lowercase italic n equals 898$ ) 和 TL ( $lowercase italic n equals 893$ ) 在孕中期母体血液和 mtDNAcn ( $lowercase italic n equals 419$ ) 和 TL ( $lowercase italic n equals 408$ ) 在脐带血中。我们使用多变量线性回归和分位数 g 计算来估计产前金属和生物标志物之间的关联。我们使用广义加性模型和贝叶斯核机器回归来检查非线性和相互作用。

结果：

母体镁含量增加 2 倍与母体降低有关 [ $β = - 0.07$ , 95% 置信区间 (CI): $negative 0.10$ , $negative 0.01$ ] 和脐带血 ( $β = - 0.08$ , 95% 置信区间: $negative 0.20$ , $negative 0.01$ ) mtDNAcn。铅与较高的母体 mtDNAcn 相关（ $lowercase beta equals 0.04$ , 95% CI: 0.01, 0.06)。硒与更长的脐带血 TL 相关（ $lowercase beta equals 0.30$ , 95% CI: 0.01 0.50)。观察到非必需金属混合物与更高的母体 mtDNAcn 之间存在关联（ $lowercase beta equals 0.04$ , 95% CI: 0.01, 0.07)。脐带血mtDNAcn与镁之间存在非线性关系；母体 mtDNAcn 和钡、铅和汞；和母体 TL 和钡。