A metabolome-wide association study of in utero metal and trace element exposures with cord blood metabolome profile: Findings from the Boston Birth Cohort. (January 2022)

• Record Type: Journal Article
• Authors: Zhang, Mingyu; Buckley, Jessie P; Liang, Liming; Hong, Xiumei; Wang, Guoying; Wang, Mei-Cheng; Wills-Karp, Marsha; Wang, Xiaobin; Mueller, Noel T
• Is Part Of: Environment international. Volume 158(2022)
• Publication Date: 2022-01
• Subjects: Pb lead -- Hg mercury -- Cd cadmium -- Se selenium -- Mn manganese -- RBC red blood cell -- WHO World Health Organization -- U.S. United States -- CDC Centers for Disease Control and Prevention -- CV coefficient of variation -- LOD limit of detection -- ICP-MS inductively coupled plasma mass spectrometry -- LC-MS liquid chromatography-tandem mass spectrometry -- BMI body mass index -- FDR false discovery rate -- CE cholesterol ester -- LPC lysophosphatidylcholine -- LPE lysophosphatidylethanolamine -- TAG triacylglycerol -- AA amino acid -- PC phosphatidylcholine -- GAA guanidinoacetic acid -- ImP imidazole propionate -- 8-OHdG 8-hydroxy-deoxyguanosine -- T2D type 2 diabetes; Heavy metals -- Lead -- Mercury -- Cadmium -- Trace elements -- Selenium -- Manganese -- Metabolome -- Metabolomics -- Metabolome-wide association study -- Child health -- Environmental health; Environmental protection -- Periodicals; Environmental health -- Periodicals; Environmental monitoring -- Periodicals; Environmental Monitoring -- Periodicals; Environnement -- Protection -- Périodiques; Hygiène du milieu -- Périodiques; Environnement -- Surveillance -- Périodiques; Environmental health; Environmental monitoring; Environmental protection; Periodicals; 333.705
• DOI: 10.1016/j.envint.2021.106976
• Languages: English
• ISSNs: 0160-4120

Abstract

Graphical abstract: Volcano plots of associations of lead (Panel A), mercury (Panel B), cadmium (Panel C), selenium (Panel D) and manganese (Panel E) with cord metabolites after Bonferroni correction for multiple comparisons. Highlights: We conducted a metabolome-wide association study to understand how in utero exposure to Pb, Hg, Cd, Se, and Mn may affect the metabolic programming of fetuses. We used data from the Boston Birth Cohort, an ongoing prospective birth cohort that comprises a predominantly urban, low-income, minority population in the United States. After Bonferroni correction, there were 25 cord metabolites associated with at least one of the metals or trace elements. Whether these metals- and trace elements-associated changes in cord metabolites can influence a child's risk of cardiometabolic diseases remains to be determined. Abstract: 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.