a1 The Liggins Institute, Faculty of Medicine and Health Science, University of Auckland, Private Bag 92019, Auckland, New Zealand
a2 Department of Pediatrics, Subdivision of Neonatology, Vrije Universiteit Medisch Centrum, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands
Urea production may be impaired in intrauterine growth restriction (IUGR), increasing the risk of toxic hyperammonaemia after birth. Arginine supplementation stimulates urea production, but its effects in IUGR are unknown. We aimed to determine the effects of IUGR and arginine supplementation on urea production and arginine metabolism in the ovine foetus. Pregnant ewes and their foetuses were catheterised at 110 days of gestation and randomly assigned to control or IUGR groups. IUGR was induced by placental embolisation. At days 120 and 126 of gestation, foetal urea production was determined from [14C]-urea kinetics and arginine metabolism was determined from the appearance of radioactive metabolites from [3H]-arginine, both at baseline and in response to arginine or an isonitrogenous mixed amino acid supplementation. Urea production decreased with gestational age in the embolised animals (13.9 ± 3.1 to 11.2 ± 3.0 μmol/kg per min, P ≤ 0.05) but not in the controls (13.3 ± 3.5 to 14.8 ± 6.0 μmol/kg per min). Arginine supplementation increased urea production in both groups, but only at 126 days of gestation (control: 15.0 ± 8.5 to 17.0 ± 9.4 μmol/kg per min; embolised: 11.7 ± 3.1 to 14.3 ± 3.1 μmol/kg per min, P ≤ 0.05). Embolisation reduced foetal arginine concentrations by 20% ( P ≤ 0.05) while foetal arginine consumption was reduced by 27% ( P ≤ 0.05). The proportions of plasma citrulline and hydroxyproline derived from arginine were reduced in the embolised animals. These data suggest that foetal urea production and arginine metabolism are perturbed in late gestation after placental embolisation.
(Received August 28 2006)
(Accepted February 07 2007)