Consequences of Perturbations of Fetal Fuels in Ovine Pregnancy

Maternal or fetal substrate infusions into chronically catheterized fetal lambs have recently been performed in order to examine the effects of excessive fetal substrate presentation on fetal metabolism and metabolic rate. The degree of maternal hyperglycemia in this animal model has been shown to relate to the degree of fetal hyperglycemia and to the magnitude of fetal glucose utilization. Series of direct fetal glucose infusions were performed designed to mimic the development of moderate maternal hyperglycemia. These studies suggest that fetal glucose excess stimulates fetal oxidative metabolism with increases in fetal glucose and lactate entry and stimulation of fetal oxygen consumption. If severe, fetal lamb hyperglycemia may result in fetal hypoxia with metabolic acidosis and fetal demise. The metabolic goal of the stimulation of fetal oxidation may relate to increases in fetal activity such as respiration, excessive fetal growth, and other factors, as yet unidentified. Insulin or catecholamines may be mediators of at least some of these events. Chronic infusion studies regarding other potential fetal fuels have not yet been performed. The chronically catheterized glucoseinfused fetal lamb may offer insights into the metabolic derangements observed and suspected in infants born to women with gestational and insulin-requiring diabetes mellitus.