Glutamine supplementation of parenteral nutrition does not improve intestinal permeability, nitrogen balance, or outcome in newborns and infants undergoing digestive-tract surgery: results from a double-blind, randomized, controlled trial. Glutamine supplementation in infants with gastrointestinal disease: a randomized, placebo-controlled pilot trial.
To assess the effect of isocaloric isonitrogenous parenteral glutamine supplementation on intestinal permeability and nitrogen loss in newborns and infants after major digestive-tract surgery.
                Glutamine supplementation in critically ill and surgical adults may normalize intestinal permeability, attenuate nitrogen loss, improve survival, and lower the incidence of nosocomial infections. Previous studies in critically ill children were limited to very-low-birthweight infants and had equivocal results.
                Eighty newborns and infants were included in a double-blind, randomized trial comparing standard parenteral nutrition (sPN; n = 39) to glutamine-supplemented parenteral nutrition (GlnPN; glutamine target intake, 0.4 g kg day; n = 41), starting on day 2 after major digestive-tract surgery. Primary endpoints were intestinal permeability, as assessed by the urinary excretion ratio of lactulose and rhamnose (weeks 1 through 4); nitrogen balance (days 4 through 6), and urinary 3-methylhistidine excretion (day 5). Secondary endpoints were mortality, length of stay in the ICU and the hospital, number of septic episodes, and usage of antibiotics and ICU resources.
                Glutamine intake plateaued at 90% of the target on day 4. No differences were found between patients assigned sPN and patients assigned GlnPN regarding any of the endpoints. Glutamine supplementation was not associated with adverse effects.
                In newborns and infants after major digestive-tract surgery, we did not identify beneficial effects of isonitrogenous, isocaloric glutamine supplementation of parenteral nutrition. Glutamine supplementation in these patients therefore is not warranted until further research proves otherwise. Glutamine (Gln) is a non-essential amino acid that plays an important role in energy metabolism for gastrointestinal epithelia and other cells with rapid turnover. We evaluated the effects of enteral supplementation with Gln in infants undergoing surgery for congenital or acquired gastrointestinal disease.
                This was a randomized, double-masked, controlled clinical trial.
                Twenty infants were randomly assigned to receive Gln (n = 9) or placebo amino acid (n = 11), with a goal of supplemental amino acid intake of 0.4 g.kg(-1).d(-1). Infants were weaned from parenteral nutrition, and enteral feeds were started according to a standardized feeding protocol. Median (interquartile range) durations of parenteral nutrition were 39 d (12 to 99) in the Gln group and 21 d (6 to 59) in the control group (P = 0.201). Median (interquartile range) durations needed to reach 80% of the US recommended dietary allowance for energy with enteral nutrition were 24 d (8 to 55) in the Gln group and 12.5 d (5 to 32) in the control group (P = 0.313). There were no differences in the occurrence of infections between groups. Among all infants enrolled, significant correlations were found between duration of parenteral nutrition and residual small bowel length, peak concentrations of direct bilirubin, and alanine aminotransferase. Peak direct bilirubin was associated with longer duration of parenteral nutrition, shorter gestation, older age before feeds were started, shorter bowel length, and larger amounts of parenteral energy and protein intake.
                In this pilot trial, enteral Gln supplementation was well tolerated among infants with surgical gastrointestinal disease. There was no effect observed on the duration of parenteral nutrition, tolerance of enteral feeds, or intestinal absorptive or barrier function. Larger, multicenter trials in infants with surgical gastrointestinal disease are needed due to the variability in important outcome measurements.
The available data from randomised controlled trials are insufficient to determine whether glutamine supplementation has any important benefits for young infants with severe gastrointestinal disease.