The studies outlined are directed at nutrient transport and its relationship to blood flow in pregnancies complicated by intrauterine growth retardation (IUGR). The transport of the 9 essential amino acids across the placenta will be studied using stable isotopes and determining the fetal/maternal enrichments and tracer concentration ratios in normal and IUGR pregnancies. IUGR pregnancies are classified by clinical severity based upon velocimetry findings and FHR data. These data on amino acid transport will be analyzed for the impact of variations in umbilical blood flow directly measured with power Doppler techniques. This will establish whether delivery of amino acids to the fetus in IUGR pregnancies is impacted by a reduction in umbilical blood flow and whether this relationship is nonlinear. The non-glucose carbohydrates including the polyols will be measured in normal and IUGR pregnancies. Specific attention is given to D-mannose and myoinositol which are studied with stable isotopes of each sugar and of D-glucose infused into the maternal circulation till steady state enrichments are established. At that time, the fetal/maternal enrichment ratios for both myoinositol and D-mannose are determined. The glucose carbon incorporation into both mannose and myoinositol will be compared in normal and IUGR pregnancies. The studies will establish which, if any, of these carbohydrates relies upon transplacental transport vs. synthesis within the fetal or placental tissues. It will determine if the transplacental gradient for some carbohydrates and polyols are increased in IUGR pregnancies as the gradient is for glucose. Finally, the impact upon the IUGR newborn of an enormous reduction in hepatic blood flow in utero will be assessed. The newborns with a marked reduction in hepatic blood flow can be detected in utero from the reduction in umbilical blood flow coupled with an increase in the ductus venosus shunt. Evidence of hepatocellular damage will be sought at delivery by analysis of cord blood for specific clotting factors and hepatic enzymes. In addition, functional disturbance in neonatal liver function will be assessed by D-galactose plasmal clearance in the newborn after a milk feeding. These studies will establish important links between blood flow changes in the fetus and nutrient delivery to the fetus.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
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Study Section
Human Embryology and Development Subcommittee 1 (HED)
Program Officer
Signore, Caroline
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University of Colorado Denver
Schools of Medicine
United States
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