On third of neonates weighing less than 2500 grams are not premature but term infants whose growth has been retarded in utero. These infants have an increased incidence of perinatal problems, decreased ultimate stature, and long-term neurologic sequelae. Growth retardation appears to be caused by an inadequate flow of nutrients and oxygen across the placenta into the fetus. We have found that concurrent, fetal gastric infusion of supplemental nutrients will prevent growth retardation in fetuses of malnourished mothers, and fetal femoral venous nutrient infusions will prevent growth retardation induced by placental embolization. In the latter infusions, placental size and umbilical blood flow were also increased.
Our aims now are to determine if supplementation: 1) will correct pre-existing growth retardation; 2) alters placental function, metabolism, cellularity or composition; 3) has similar effects on maternal and fetal portions of the placenta; 4) enhances growth by action of glucose alone, amino acids alone, or the total calories infused; 5) effects growth through changes in placental or feta secretion of growth promoting hormones; and 6) can be given through other routes. Characterized, pregnant sheep will be prospectively followed over the third trimester. We will compare: normal animals; animals growth retarded by placental embolization; and embolized animals with evidence of growth retardation, then given in utero supplements. Equal caloric infusions of either glucose or amino acids will initially be given via the fetal femoral vein; alternate routes will be used in later studies. In all groups we will follow: fetal growth (the in utero change in girth, change in crown-rump and hindlimb length, birth weight); maternal weight; fetal and maternal metabolite and hormone levels; umbilical and uteroplacental blood flow and blood flow distribution in the placenta and uterus; umbilical, uteroplacental and placental uptake of substrates; placental composition and cellularity; and fetal organ size, composition, cellularity and maturity. Metabolites measured will be: glucose, alpha amino nitrogen, individual amino acids, lactate, urea, ammonia, total protein, hemoglobin, oxygen content, pH, PaO2, PCO2, and hematocrit. Hormones measured will be GH, insulin, somatomedin-C/IGF1, prolactin, and oCS. Maternal and fetal blood flow will be determined prospectively with an antipyrine technique; flow distribution will be determined with radiolabelled microspheres. Fetal brain, liver and lung, and maternal and fetal placental tissues will be analyzed for DNA, protein, and water; where relevant glycogen and saturated phosphatidylcholine will be measured.
