Periconceptional and prenatal nutrition shapes the fetal epigenomic landscape

Nutrition during pregnancy can influence fetal development and health across the lifespan. Prenatal nutrition is mechanistically linked to the epigenetic landscape because nutrients supply methyl groups and regulate microRNAs and proteins involved in epigenetic modifications. This review focuses on the epigenomic landscape in both the umbilical cord blood, as a window into fetal development, and in the placenta, as the master regulator of fetal nutrition. We highlight associations between the epigenome and nutrients found in prenatal multiple micronutrient supplements, including one carbon metabolism nutrients, antioxidant vitamins, vitamin D, trace minerals, and omega-3 polyunsaturated fatty acids. We discuss challenges in this field including reliance on observational studies, non-linear relationships, cell type-specific effects, and sex-specific effects. We also highlight emerging approaches to explore the role of nutritional epigenomics in development including critical windows of exposure and novel epigenetic and epitranscriptomic features by applying new technological advancements. A better understanding of how nutrients affect the epigenomic landscape in early life can inform further mechanistic studies and improve clinical guidance surrounding nutrient and intake during pregnancy, ultimately leading to improved maternal and fetal outcomes and health throughout the lifespan.