Causal Mediation Analysis in Pregnancy Studies: the Case of Environmental Epigenetics

Abstract

Purpose of Review

Studies on the mechanisms of action of environmental exposures in pregnancy are increasingly popular. In particular, it is of interest to investigate the role of genetic and epigenetic factors as mediators of the maternal environmental exposures’ effects on perinatal outcomes. Causal mediation analysis lies at the center of environmental epigenetics research, and the methodological challenges that arise in this context have not yet been fully articulated.

Recent Findings

Measurement error, unmeasured confounding, reverse causation, and multiple mediators are often disregarded issues in environmental epigenetic studies that can lead to important biases. Considering the study of maternal smoking effect on birth weight potentially mediated by DNA methylation as example, I discuss the impact of these phenomena on estimation and testing of causal pathways. Statistical methods have been recently introduced to account for these frequently encountered issues.

Summary

Causal interpretation of pregnancy studies on the role epigenetic factors as mediators of environmental exposures effects can be improved by the adoption of recent methodological advancements in mediation analysis that correct for measurement error, use genetic instrumental variables, and account for the presence of multiple mediators.

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