High-resolution metabolomics of exposure to tobacco smoke during pregnancy and adverse birth outcomes in the Atlanta African American Maternal-Child cohort 公开
Tan, Youran (Spring 2021)
Abstract
Background: 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. To help close this gap, we conducted a metabolome-wide association study (MWAS) to identify the metabolic perturbations and potential biomarkers underlying the association between cotinine, a widely used biomarker of tobacco exposure, and adverse birth outcomes.
Methods: 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 (preterm birth, early term birth vs. full term birth; gestational age at birth) 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.
Results: The median maternal urinary cotinine concentrations were 5.93 ug/g creatinine and 3.69 ug/g creatinine in early and late pregnancy, respectively, with a total of 29 women having higher than 100 ug/g creatinine concentration. In total, 16,481 and 13,043 metabolic features were identified in serum samples at each visit using liquid chromatography-high resolution mass spectrometry with positive and negative electrospray ionization (ESI) modes, respectively. Thirteen metabolic pathways were found to be associated with 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 exposure, preterm birth, and shorter gestational length, including glutamate, serine, choline, and taurine. The identified metabolites are closely involved in endogenous inflammation, vascular reactivity, and lipid peroxidation processes.
Conclusions: The metabolic perturbations associated with cotinine exposure were related to inflammation, oxidative stress, placental vascularization, and insulin action, which could contribute to shorter gestations. These findings support the future development of targeted interventions to reduce adverse birth outcomes associated with tobacco smoke exposure, especially among African American women who are disproportionately exposed to high tobacco smoke and experience higher rates of adverse birth outcomes.
Table of Contents
BACKGROUND ........................................................................................................................ 1
METHODS ................................................................................................................................ 7
Study Population ............................................................................................................................... 7
Measurement of Maternal Cotinine Concentrations ..................................................................... 7
Measure of Adverse Birth Outcomes and Other Factors.............................................................. 8
Untargeted High-Resolution Metabolomics Analysis .................................................................... 8
Statistical Analyses............................................................................................................................ 9
Metabolic Pathway Enrichment Analysis and Metabolite Annotation ..................................... 10
Meet-in-the-middle Analysis .......................................................................................................... 11
RESULTS ................................................................................................................................ 12
MWAS Model .................................................................................................................................. 12
Pathway Enrichment Analysis ....................................................................................................... 13
Metabolite Annotation .................................................................................................................... 14
Sensitivity Analysis ......................................................................................................................... 15
DISCUSSION ......................................................................................................................... 16
FUTURE WORK ............................................................................................................................ 22
REFERENCES ....................................................................................................................... 23
TABLES AND FIGURES ...................................................................................................... 29
APPENDIX ............................................................................................................................. 39
About this Master's Thesis
| School | |
|---|---|
| Department | |
| Subfield / Discipline | |
| Degree | |
| Submission | |
| Language |
|
| Research Field | |
| 关键词 | |
| Committee Chair / Thesis Advisor | |
| Committee Members |
Primary PDF
| Thumbnail | Title | Date Uploaded | Actions |
|---|---|---|---|
|
|
High-resolution metabolomics of exposure to tobacco smoke during pregnancy and adverse birth outcomes in the Atlanta African American Maternal-Child cohort () | 2021-04-30 16:58:47 -0400 |
|
Supplemental Files
| Thumbnail | Title | Date Uploaded | Actions |
|---|