Air Pollution and Adverse Pregnancy and Birth Outcomes: Mediation Analysis Using Metabolomic Profiles

Kosuke Inoue, Qi Yan, Onyebuchi A. Arah, Kimberly Paul, Douglas I. Walker, Dean P. Jones, Beate Ritz

Research output: Contribution to journalReview articlepeer-review

24 Scopus citations


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. Summary: 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.

Original languageEnglish
Pages (from-to)231-242
Number of pages12
JournalCurrent Environmental Health Reports
Issue number3
StatePublished - 1 Sep 2020


  • 4-way decomposition
  • Adverse birth outcomes
  • Air pollution
  • Causal mediation analysis
  • Metabolomics


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