Epigenetic Embodiment of Health and Disease: A Framework for Nutritional Intervention (WP-12-15)
Christopher Kuzawa and Zaneta Thayer
Evidence that fetal nutrition influences epigenetic profiles and adult health has heightened interest in pregnancy nutritional interventions. However, like all placental mammals, the human fetus is buffered against short-term nutritional fluctuations by maternal physiology. We review evidence that nutritional buffering reflects a broader capacity to buffer fetal biology from environmental fluctuations that varies by exposure. At one extreme are evolutionarily-novel teratogens that the placenta and mother’s body have minimal capacity to shield the fetus from, making them excellent targets for intervention during pregnancy. At the other extreme are macronutrients homeostatically maintained by maternal metabolism. For macronutrients like glucose, the diet is only one of multiple sources, and temporary deficits may be redressed using maternal stores and endogenous synthesis. Fetal experience of maternal pregnancy supplementation will be tempered by these buffering mechanisms. We propose that strategies to improve fetal macronutrient delivery should strive to modify maternal metabolism, in addition to targeting her pregnancy macronutrient intake. We review evidence that sustained improvements in early life nutrition of future mothers hold promise to improve fetal nutrition and epigenetic profiles in future generations.