A metabolome-wide association study of in utero metal and trace element exposures with cord blood metabolome profile: Findings from the Boston Birth Cohort,Environment International

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A metabolome-wide association study of in utero metal and trace element exposures with cord blood metabolome profile: Findings from the Boston Birth Cohort
Environment International ( IF 10.3 ) Pub Date : 2021-11-19 , DOI: 10.1016/j.envint.2021.106976
Mingyu Zhang ₁ , Jessie P Buckley ₂ , Liming Liang ₃ , Xiumei Hong ₄ , Guoying Wang ₄ , Mei-Cheng Wang ₅ , Marsha Wills-Karp ₆ , Xiaobin Wang ₇ , Noel T Mueller ₁

Affiliation

Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, MD, USA.
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Center on the Early Life Origins of Disease, Department of Population, Family and Reproductive Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Center on the Early Life Origins of Disease, Department of Population, Family and Reproductive Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, MD, USA.

Background

Exposure to metals lead (Pb), mercury (Hg), and cadmium (Cd) and trace elements selenium (Se) and manganese (Mn) has been linked to the developmental origins of cardiometabolic diseases, but the mechanisms are not well-understood.

Objective

Conduct a metabolome-wide association study to understand how in utero exposure to Pb, Hg, Cd, Se, and Mn affects the metabolic programming of fetuses.

Methods

We used data from the Boston Birth Cohort, which enrolled mother-child pairs from Boston, MA. We measured metals and trace elements in maternal red blood cells (RBCs) collected 24–72 h after delivery, and metabolites in cord blood collected at birth. We used multivariable linear regression to examine associations of metals and trace elements with metabolites and Bonferroni correction to account for multiple comparisons. We assessed non-linear associations of metals and trace elements with metabolites using restricted cubic spline plots.

Results

This analysis included 670 mother-child pairs (57% non-Hispanic Black and 24% Hispanic). After Bonferroni correction, there were 25 cord metabolites associated with at least one of the metals or trace elements. Pb was negatively associated with the xenobiotic piperine, Cd was positively associated with xenobiotics cotinine and hydroxycotinine, and Hg was associated with 8 lipid metabolites (in both directions). Se and Mn shared associations with 6 metabolites (in both directions), which mostly included nucleotides and amino acids; Se was additionally associated with 7 metabolites (mostly amino acids, nucleotides, and carnitines) and Mn was additionally associated with C36:4 hydroxy phosphatidylcholine. Restricted cubic spline plots showed that most associations were linear.

Discussion

Maternal RBC metal and trace element concentrations were associated in a dose-dependent fashion with cord blood metabolites. What remains to be determined is whether these metals- and trace elements-associated changes in cord metabolites can influence a child’s risk of cardiometabolic diseases.

中文翻译：

子宫内金属和微量元素暴露与脐带血代谢组概况的全代谢组关联研究：来自波士顿出生队列的发现

背景

暴露于金属铅 (Pb)、汞 (Hg) 和镉 (Cd) 以及微量元素硒 (Se) 和锰 (Mn) 与心脏代谢疾病的发展起源有关，但其机制尚不清楚。

客观的

进行代谢组范围的关联研究，以了解在子宫内暴露于 Pb、Hg、Cd、Se 和 Mn 如何影响胎儿的代谢程序。

方法

我们使用了来自波士顿出生队列的数据，该队列招募了来自马萨诸塞州波士顿的母子对。我们测量了分娩后 24-72 小时收集的母体红细胞 (RBC) 中的金属和微量元素，以及出生时收集的脐带血中的代谢物。我们使用多变量线性回归来检查金属和微量元素与代谢物的关联，并使用 Bonferroni 校正来解释多重比较。我们使用受限三次样条图评估了金属和微量元素与代谢物的非线性关联。

结果

该分析包括 670 对母子（57% 非西班牙裔黑人和 24% 西班牙裔）。在 Bonferroni 校正后，有 25 种脐带代谢物与至少一种金属或微量元素相关。Pb 与外源性胡椒碱呈负相关，Cd 与外源性可替宁和羟可替宁呈正相关，Hg 与 8 种脂质代谢物（双向）相关。Se 和 Mn 与 6 种代谢物（双向）共享关联，其中主要包括核苷酸和氨基酸；Se 还与 7 种代谢物（主要是氨基酸、核苷酸和肉毒碱）相关，Mn 还与 C36:4 羟基磷脂酰胆碱相关。受限三次样条图显示大多数关联是线性的。