High-resolution metabolomics of exposure to tobacco smoke during pregnancy and adverse birth outcomes in the Atlanta African American maternal-child cohort. (1st January 2022)

• Record Type: Journal Article
• Authors: Tan, Youran; Barr, Dana Boyd; Ryan, P. Barry; Fedirko, Veronika; Sarnat, Jeremy A.; Gaskins, Audrey J.; Chang, Che-Jung; Tang, Ziyin; Marsit, Carmen J.; Corwin, Elizabeth J.; Jones, Dean P.; Dunlop, Anne L.; Liang, Donghai
• Is Part Of: Environmental pollution. Volume 292:Part A(2022)
• Publication Date: 2022-01-01
• Subjects: Tobacco smoke exposure -- High-resolution metabolomics -- Cotinine -- Preterm birth -- Shorter gestational age; Pollution -- Periodicals; Pollution -- Environmental aspects -- Periodicals; Environmental Pollution -- Periodicals; Pollution -- Périodiques; Pollution -- Aspect de l'environnement -- Périodiques; Pollution -- Effets physiologiques -- Périodiques; Pollution; Pollution -- Environmental aspects; Periodicals; Electronic journals; 363.73
• DOI: 10.1016/j.envpol.2021.118361
• Languages: English
• ISSNs: 0269-7491

Abstract

Abstract: Exposure to tobacco smoke during pregnancy has been associated with a series of adverse reproductive outcomes; however, the underlying molecular mechanisms are not well-established. We conducted an untargeted metabolome-wide association study to identify the metabolic perturbations and molecular mechanisms underlying the association between cotinine, a widely used biomarker of tobacco exposure, and adverse birth outcomes. We collected early and late pregnancy urine samples for cotinine measurement and serum samples for high-resolution metabolomics (HRM) profiling from 105 pregnant women from the Atlanta African American Maternal-Child cohort (2014–2016). Maternal metabolome perturbations mediating prenatal tobacco smoke exposure and adverse birth outcomes were assessed by an untargeted HRM workflow using generalized linear models, followed by pathway enrichment analysis and chemical annotation, with a meet-in-the-middle approach. The median maternal urinary cotinine concentrations were 5.93 μg/g creatinine and 3.69 μg/g creatinine in early and late pregnancy, respectively. In total, 16, 481 and 13, 043 metabolic features were identified in serum samples at each visit from positive and negative electrospray ionization modes, respectively. Twelve metabolic pathways were found to be associated with both cotinine concentrations and adverse birth outcomes during early and late pregnancy, including tryptophan, histidine, urea cycle, arginine, and proline metabolism. We confirmed 47 metabolites associated with cotinine levels, preterm birth, and shorter gestational age, including glutamate, serine, choline, and taurine, which are closely involved in endogenous inflammation, vascular reactivity, and lipid peroxidation processes. The metabolic perturbations associated with cotinine levels were related to inflammation, oxidative stress, placental vascularization, and insulin action, which could contribute to shorter gestations. The findings will support the further understanding of potential internal responses in association with tobacco smoke exposures, especially among African American women who are disproportionately exposed to high tobacco smoke and experience higher rates of adverse birth outcomes. Graphical abstract: Image 1 Highlights: Metabolic perturbation associated with cotinine may contribute to shorter gestation. Urea cycle and amino metabolism associated with both cotinine and birth outcomes. 47 metabolic features were confirmed at level 1 confidence. Metabolites mostly involved in oxidative stress and placental vascularization.