The focus of this Program Grant is metabolic regulation of fetal growth, emphasizing experiments in comparative reproductive and developmental physiology to determine pathogenesis and metabolic consequences of fetal growth restriction (FGR). FGR affects a large number of human pregnancies and is responsible for increased fetal, neonatal, and adult morbidity and mortality. Three Projects will address the following experimental aims and hypotheses: 1. in pregnant sheep, deprivation of glucose and amino acid supply to the fetus produces fetal insulin deficiency and insulin resistance, resulting in FGR and a limitation to nutrient therapy; 2. in pregnant sheep, placental insufficiency from abnormal growth and function produces severe FGR and limitation to nutrient therapy; 3. clinical studies in normal and FGR pregnancies are directed at fetal surveillance and fetal and placental amino acid metabolism using techniques comparable to those in the animal models, and also provide measures of placental and fetal responses to nutrient therapy. The animal studies are supported by the UCHSC Perinatal Research Facility. Clinical studies are conducted at the University of Milan, Italy, and in the UCHSC Obstetrics Service at University Hospital. The Program is supported by an Administrative Core, a Laboratory Core, and a Statistical Core. Understanding metabolic causes and consequences of FGR and mechanisms by which nutrient therapy affects placental and fetal metabolism and growth through integration of the basic and clinical research in the Program should lead to more rational preventative and therapeutic measures to diminish the severity of FGR and thus to improve fetal and neonatal survival and health.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Program Projects (P01)
Project #
5P01HD020761-14
Application #
2888909
Study Section
Maternal and Child Health Research Committee (HDMC)
Program Officer
Catz, Charlotte S
Project Start
1985-09-30
Project End
2001-06-30
Budget Start
1999-07-01
Budget End
2000-06-30
Support Year
14
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Colorado Denver
Department
Pediatrics
Type
Schools of Medicine
DUNS #
065391526
City
Aurora
State
CO
Country
United States
Zip Code
80045
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
Manco-Johnson, Marilyn J; Hacker, Michele R; Jacobson, Linda J et al. (2009) Pharmacokinetics of protein C and antithrombin in the fetal lamb: a model to predict human neonatal replacement dosing. Neonatology 95:279-85
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
Paolini, C L; Teng, C; Jozwik, M et al. (2003) Umbilical threonine uptake during maternal threonine infusion in sheep. Placenta 24:354-60
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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