Asymptomatic Hyperammonemia in Low Birthweight Infants

Abstract

SummaryAt 0-3 days of age the plasma ammonium concentration in full term appropriate for gestational age (AGA) infants was (mean 2 SEM) 27.5 & 0.5 pM; a value similarlo that reported * in adults. Ammonium levels in low birthweight AGA and SGA groups were 47.0 + 2.0 p M and 45.1 r 3.3 p M respectively; significantly elevated (P < 0.001) as compared to the full term group. These increased ammonium levels persisted at 3-5 weeks of age. Associated with the hyperammonemia was a significant (P < 0.01) decrease in plasma a-ketoglutarate concentration:11.8 r 1.0 pM, in the low birthweight AGA as compared to 20.7 r 0.6 p M in the full term AGA infants. There was an inverse linear correlation between ~l a s m a concentrations of ammonium and a-ketoglutarate r = -0.86, P < 0.001. Urinary orotate excretion was significantly elevated (P < 0.05) in low birthweight AGA infants. There was no difference in the plasma concentrations of glutamine, glutamate, or alanine among the various groups. Hyperammonemia was not associated with neurologic dysfunction. SpeculationThere is a greater accumulation of ammonium in low birthweight as compared to full term infants. This may be a consequence of a developmental delay of one or more of the enzymes required for urea synthesis. Alternatively, the hyperammonemia may be related to arginine andlor ornithine diversion out of the cycle and incomplete repletion of ornithine from glutamate via the A'-pyrroline-5-carboxylate pathway.were measured once or twice a week on capillary blood during the first 2 months of life. Plasma a-ketoglutarate concentration and urinary orotate excretion were also measured at 0-3 days of age in 30 infants. Plasma ammonium determinations were performed within 30 min of blood drawing using a cation exchange resin, AS previobsly described (3). The normal adult range is 15-33 pM. Glutamine (18), glutamate (4), alanine (30), and a-ketoglutarate (16) were measured by modifications of enzymatic fluorometric techniques, allowing capillary plasma to be used. Urinary orotate was measured by the method of Goldstein et al. (11). A neurologic examination as described by Prechtl and Beintema (20) was performed on the low birthweight infants at 0-3 days of age. RESULTSThe full term group consisted of 25 males (22 were black) and 27 females (25 were black); the low birthweight groups consisted of 14 males (11 were black) and 22 females (20 were black).Birthweights of the groups were (mean + SEM): full term 3261 + 59 g, low birthweight SGA 1848 + 185 g, and low birthweight AGA 1963 + 79 g. Gestational age in the groups were (mean + SD): full term AGA 39 + 1.5 weeks, low birthweight SGA 37 + 3 weeks and low birthweight AGA 33 + 2.5 weeks. All infants received a proprietary milk formula (Similac) containing 1.5 g protein/100 ml, 18 parts bovine whey protein to 82 parts bovine caseins. Mean protein intake was similar in all groups at 3-5 weeks of age (3.0 g/kg/day) and was higher in the full term group during the first 3 days of life (1.7 compared to 1.2 &kg/ day). At 0-3 days of age,...

Intestinal arginine metabolism during development

“…This hyperammonemia is apparently not a consequence of a low level of hepatic urea cycle enzymes but due to a low plasma concentration of L-arginine and L-ornithine [51, 521. It has been speculated that hyperammonemia in low-birth-weight infants may be due to an incomplete repletion of L-arginine in the liver urea cyle [51,6]. The capacity for L-arginine production in enterocytes isolated from newborn pigs could then be related to protein synthesis during development andor to the formation of urea-cycle intermediates in the liver where urea cycle enzymes are already high at birth compared to the values recorded in the adult pig [53].…”

“…This would allow de novo net synthesis of L-arginine from various precursors (L-citrulline, L-ornithine) which are present in milk [50] or in plasma [43]. In this context, in premature or low-birth-weight infants, a moderate and transient hyperammonemia that is reversible by L-arginine is often observed [51,521. This hyperammonemia is apparently not a consequence of a low level of hepatic urea cycle enzymes but due to a low plasma concentration of L-arginine and L-ornithine [51, 521.…”

Within-litter variation in birth weight: impact of nutritional status in the sow

“…We detected an abnormally high activity of glutamate oxaloacetate transaminase in the liver of IUGR fetuses compared with normal fetuses at Day 110 of gestation, this enzyme being responsible for the generation of ammonia from glutamate . High levels of expression of glutamate dehydrogenase 1, coupled with reduced levels of carbomoyphosphate synthase 1 to degrade it, result in the accumulation of ammonia, which increases the risk of hyperammonemia in low-birth-weight piglets and low-birth-weight human infants (Batshaw and Brusilow, 1978). This condition severely threatens survival of the neonate.…”

Altered Mental Status in a Teenager

“…The differential diagnosis of hyperammonemia in the pediatric population includes transient hyperammonemia of the neonate and a large number of IEMs, including organicacidopathies, urea cycle defects, congenital lactic acidosis, and some aminoacidopathies (2 ). The immature liver in the newborn period with concomitant immature urea cycle enzymes or a generalized liver dysfunction may also contribute.…”