Arginine-responsive asymptomatic hyperammonemia in the premature infant

We found that more than 50% of premature infants have elevated plasma ammonium levels during the first 2 months of life. Ammonium levels were twice normal and were unaccompanied by clinical symptoms of vomiting or lethargy. Ten of these infants were given supplements of arginine (1 to 2 mmol/kg/day PO) for 1 to 2 weeks preceded and followed by control periods. In each infant, plasma ammonium levels fell significantly within 2 days of start of arginine supplementation, and increased once arginine was discontinued. We studied 59 additional premature infants, of whom 26 had normal ammonium levels and 33 were hyperammonemic. Plasma arginine and ornithine levels were significantly lower in the hyperammonemic group, but there was no difference in urinary excretion of arginine or ornithine between groups. Half of the hyperammonemic infants received arginine supplementation between 2 and 8 weeks of age. Plasma ammonium levels in the arginine group was 33+1 μmol/L, compared to 45+2 μmol/L in the untreated group. Follow-up at 18 months of age showed similar IQ scores in all groups, suggesting that significant neurologic deficits do not result from this transient metabolic defect. The mechanism of the hyperammonemia is unclear.