010. PERICONCEPTIONAL UNDERNUTRITION: LIFE-LONG EFFECTS FOR THE OFFSPRING

Abstract

Poor nutrition in women of child-bearing age is common, even in Western countries. It has been estimated that approximately 30% of women of child-bearing age in affluent cities such as Sydney and Southampton are either actively dieting or have a nutritional intake that does not meet daily recommended requirements for all nutrients. We have investigated the effect of reduced maternal nutrition before and around the time of conception on fetal growth and development, and have followed offspring through to adulthood. In this paradigm, ewes were fed to lose 10–15% of their body weight and then to gain weight according to conceptus mass. Control ewes were well fed throughout. Different timing and duration of undernutrition in the periconceptional period were utilised to investigate the most critical window for fetal development. Periconceptional undernutrition resulted in accelerated development of the fetal hypothalamic-pituitary-adrenal (HPA) and glucose-insulin axes in late gestation, and preterm birth. Offspring of periconceptionally undernourished ewes demonstrated altered laterality and an altered response to isolation stress; HPA axis function was also suppressed. As offspring aged, glucose tolerance decreased and became significantly impaired by young adulthood compared with control offspring. The effects of maternal undernutrition on offspring were modified by offspring sex and also by being one of a twin pair. Interestingly, our data also demonstrate that conception as a twin, regardless of maternal nutritional status, also affects all these outcomes but in a different way to maternal undernutrition. Preliminary data suggest that epigenetic changes in feeding centres of the hypothalamus may play a role in the mechanism behind some of these effects. These studies suggest that even moderate maternal undernutrition in very early pregnancy has life-long effects. Should this also be true in humans, then health care messages for women may need to be targeted prior to pregnancy.