One-third of small infants born weighing less than 2,500 grams are not premature but term infants whose growth has been retarded in utero. These infants have a greatly increased incidence of intrapartum asphyxia, neonatal morbidity, neurologic abnormalities and decreased brain cellularity. Intrauterine growth retardation appears to be caused by inadequate flow of nutrients and oxygen from mother to fetus, across the placenta. The metabolic alterations and changes in umbilical uptake of nutrients and oxygen that occur, as growth retardation develops, are unclear. Some types of growth retardation, may be reversible by providing paraplacental nutritional supplements. We propose to evaluate the effects of long-term nutritional therapy on fetuses growth retarded because of maternal malnutrition, fetuses growth retarded because of microinfraction of the placenta and normal control fetuses. Using a chronic pregnant sheep preparation, with indwelling catheters, we will prospectively follow fetal growth and metabolism, over the six week long third trimester. Some fetuses will be growth retarded by restricting maternal intake of protein and calories and others by embolization of the maternal side of the placenta. The normal fetuses and fetuses being growth retarded by each method will be separated into four groups for evaluation of nutritional supplementation: 1) those receiving intragastric supplements; 2) those receiving introamniotic supplements; 3) those receiving umbilical venous supplements; and 4) those not supplemented. Nutritional supplements will contain a balance of amino acids, glucose and acetate and will be infused continuously over the last month of gestation. In all animals we will follow: fetal weight; fetal length; hindlimb length; maternal weight; metabolite levels in fetal blood, maternal blood and amniotic fluid; nutrient delivery to fetal organs; and umbilical uptake of nutrients. Metabolities measured will be: glucose, amino nitrogen, alanine, lactate, free fatty acids, acetate, Beta hydroxybutyrate, albumin, urea, oxygen and blood gases. At birth fetal organ weights, DNA and protein content will be determined as well as fetal fat, water and ash content.
| Simmons, R A; Charlton, V E (1990) Late gestation alterations in fetal pulmonary lactate metabolism in vivo. Pediatr Res 27:274-7 |
