Contrasting the effects of intra-uterine smoking and one-carbon micronutrient exposures on offspring DNA methylation

Maternal smoking and micronutrient intake during pregnancy are two strong biological candidates for impacting the developing epigenome. The extent to which DNA methylation in offspring is modified by these intrauterine exposures has not been presented in parallel. In this review, we summarize human studies which have investigated genome-wide DNA methylation in the offspring in relation to maternal smoking and one-carbon micronutrient exposure during pregnancy. We contrast the primarily independent efforts for these two categories of exposure, and potential explanations for these differences. We emphasize methodological considerations such as power to detect methylation signals, exposure assessment, control of sources of variability, causal inference and the role of observed methylation changes in mediating downstream outcomes in the offspring.