Kosuke Inoue1, Qi Yan1, Onyebuchi A Arah1,2,3, Kimberly Paul1, Douglas I Walker4, Dean P Jones5,6, Beate Ritz7,8,9. 1. Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles (UCLA), 650 Charles E. Young Dr. South, Los Angeles, CA, 90095, USA. 2. Department of Statistics, UCLA College of Letters and Science, Los Angeles, CA, USA. 3. Department of Public Health, Aarhus University, Aarhus, Denmark. 4. Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 5. Clinical Biomarkers Laboratory, Division of Pulmonary, Allergy, and Critical Care Medicine, School of Medicine, Emory University, Atlanta, GA, USA. 6. Department of Medicine, Emory University, Atlanta, GA, USA. 7. Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles (UCLA), 650 Charles E. Young Dr. South, Los Angeles, CA, 90095, USA. britz@ucla.edu. 8. Department of Environmental Health Sciences, UCLA Fielding School of Public Health, Los Angeles, CA, USA. britz@ucla.edu. 9. Department of Neurology, UCLA David Geffen School of Medicine, Los Angeles, CA, USA. britz@ucla.edu.
Abstract
PURPOSE OF REVIEW: Review how to use metabolomic profiling in causal mediation analysis to assess epidemiological evidence for air pollution impacts on birth outcomes. RECENT FINDINGS: Maternal exposures to air pollutants have been associated with pregnancy complications and adverse pregnancy and birth outcomes. Causal mediation analysis enables us to estimate direct and indirect effects on outcomes (i.e., effect decomposition), elucidating causal mechanisms or effect pathways. Maternal metabolites and metabolic pathways are perturbed by air pollution exposures may lead to adverse pregnancy and birth outcomes, thus they can be considered mediators in the causal pathways. Metabolomic markers have been used to explain the biological mechanisms linking air pollution and respiratory function, and of arsenic exposure and birth weight. However, mediation analysis of metabolomic markers has not been used to assess air pollution effects on adverse birth outcomes. In this article, we describe the assumptions and applications of mediation analysis using metabolomic markers that elucidate the potential mechanisms of the effects of air pollution on adverse pregnancy and birth outcomes. The hypothesis of mediation along specified pathways can be assessed within the structural causal modeling framework. For causal inferences, several assumptions that go beyond the data-including no uncontrolled confounding-need to be made to justify the effect decomposition. Nevertheless, studies that integrate metabolomic information in causal mediation analysis may greatly improve our understanding of the effects of ambient air pollution on adverse pregnancy and birth outcomes as they allow us to suggest and test hypotheses about underlying biological mechanisms in studies of pregnant women.
PURPOSE OF REVIEW: Review how to use metabolomic profiling in causal mediation analysis to assess epidemiological evidence for air pollution impacts on birth outcomes. RECENT FINDINGS: Maternal exposures to air pollutants have been associated with pregnancy complications and adverse pregnancy and birth outcomes. Causal mediation analysis enables us to estimate direct and indirect effects on outcomes (i.e., effect decomposition), elucidating causal mechanisms or effect pathways. Maternal metabolites and metabolic pathways are perturbed by air pollution exposures may lead to adverse pregnancy and birth outcomes, thus they can be considered mediators in the causal pathways. Metabolomic markers have been used to explain the biological mechanisms linking air pollution and respiratory function, and of arsenic exposure and birth weight. However, mediation analysis of metabolomic markers has not been used to assess air pollution effects on adverse birth outcomes. In this article, we describe the assumptions and applications of mediation analysis using metabolomic markers that elucidate the potential mechanisms of the effects of air pollution on adverse pregnancy and birth outcomes. The hypothesis of mediation along specified pathways can be assessed within the structural causal modeling framework. For causal inferences, several assumptions that go beyond the data-including no uncontrolled confounding-need to be made to justify the effect decomposition. Nevertheless, studies that integrate metabolomic information in causal mediation analysis may greatly improve our understanding of the effects of ambient air pollution on adverse pregnancy and birth outcomes as they allow us to suggest and test hypotheses about underlying biological mechanisms in studies of pregnant women.
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