The specific aims of this project involve clinical studies in normal pregnancies and pregnancies complicated by fetal growth restriction. The study of in vivo amino acid placental transport and metabolism follow-up observations that fetal amino acid concentrations are significantly reduced in fetal growth restricted pregnancies. A non steady state study utilizing stable isoptomers of essential and nonessential amino acids in pregnant women scheduled for cordocentesis examines in vivo transport rates for different groups of amino acids; a.) to define differences in their relative rates of in vivo transport and b.) to test whether amino acid transport is reduced in FGR pregnancies compared to normal pregnancies for all amino acids or a specific subset. Steady state stable isotope methodology is also used to test whether the fetal maternal enrichment ratios for stable isoptomers of amino acids infused into the maternal circulation is lower in FGR pregnancies reflecting decreased transport and increased protein turnover. The relationship of maternal concentration to umbilical uptake for normal and FGR pregnancies is also investigated utilizing data on umbilical arterial venous differences determined at the time of cesarean section. Finally the role of direct measurements of umbilical venous blood flow compared to arterial velocemetry measurements and fetal blood chemistry is examined around the framework of the classification of clinical severity in FGR pregnancies.

Project Start
Project End
Budget Start
Budget End
Support Year
11
Fiscal Year
1996
Total Cost
Indirect Cost
Regnault, Timothy R H; de Vrijer, Barbra; Galan, Henry L et al. (2013) Umbilical uptakes and transplacental concentration ratios of amino acids in severe fetal growth restriction. Pediatr Res 73:602-11
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Timmerman, M; Wilkening, R B; Regnault, T R H (2003) Induction of glutamate dehydrogenase in the ovine fetal liver by dexamethasone infusion during late gestation. Exp Biol Med (Maywood) 228:100-5
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Wilkes, Paul T; Meschia, Giacomo; Teng, Cecilia et al. (2003) The effect of an elevated maternal lysine concentration on placental lysine transport in pregnant sheep. Am J Obstet Gynecol 189:1494-500
Ferrazzi, E; Bozzo, M; Rigano, S et al. (2002) Temporal sequence of abnormal Doppler changes in the peripheral and central circulatory systems of the severely growth-restricted fetus. Ultrasound Obstet Gynecol 19:140-6
Teng, Cecilia C; Tjoa, Susan; Fennessey, Paul V et al. (2002) Transplacental carbohydrate and sugar alcohol concentrations and their uptakes in ovine pregnancy. Exp Biol Med (Maywood) 227:189-95
Teng, Cecilia; Battaglia, Frederick C; Meschia, Giacomo et al. (2002) Fetal hepatic and umbilical uptakes of glucogenic substrates during a glucagon-somatostatin infusion. Am J Physiol Endocrinol Metab 282:E542-50
Regnault, T R H; Orbus, R J; de Vrijer, B et al. (2002) Placental expression of VEGF, PlGF and their receptors in a model of placental insufficiency-intrauterine growth restriction (PI-IUGR). Placenta 23:132-44
Paolini, C L; Marconi, A M; Pike, A W et al. (2001) A multiple infusion start time (MIST) protocol for stable isotope studies of fetal blood. Placenta 22:171-6

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