Glutamine supplementation to prevent morbidity and mortality in preterm infants

Glutamine endogenous biosynthesis may be insufficient for tissue needs in states of metabolic stress. Trials in adults have suggested that glutamine supplementation improves clinical outcomes in critically ill adults. It has been suggested that glutamine supplementation may benefit preterm infants, particularly very low birth weight infants.

To determine the effects of glutamine supplementation on mortality and morbidity in preterm infants.

We used the standard search strategy of the Cochrane Neonatal Review Group. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2004), MEDLINE (1966 - August 2004), EMBASE (1980 - August 2004), conference proceedings, and previous reviews.

Randomised or quasi-randomised controlled trials that compared glutamine supplementation versus no glutamine supplementation in preterm babies at any time from birth to discharge from hospital.

We extracted the data using the standard methods of the Cochrane Neonatal Review Group, with separate evaluation of trial quality and data extraction by two reviewers, and synthesis of data using relative risk, risk difference and weighted mean difference.

More than 2300 infants have participated in six randomised controlled trials. All of the participating infants were of very low birth weight. Three trials assessed enteral glutamine supplementation, and three trials assessed parenteral glutamine supplementation. These trials were generally of good methodological quality with adequate allocation concealment, blinding of care-givers and assessors to the intervention, and complete or near-complete follow-up of recruited infants. We found that glutamine supplementation does not have a statistically significant effect on mortality: typical relative risk 0.98 (95% confidence interval 0.80 to 1.21); typical risk difference 0.00 (95% confidence interval -0.03 to 0.03). One of the trials assessed longer term neurodevelopmental outcomes (Poindexter 2004). The investigators reported that they did not find any statistically significant differences in various assessments of neurodevelopment (including Bayley scales) on follow up at 18 months corrected age. We found that glutamine supplementation does not have a statistically significant effect on the incidence of systemic infection (typical relative risk 1.02 (95% confidence interval 0.92 to 1.13); typical risk difference 0.01 (95% confidence interval -0.03 to 0.05)), necrotising enterocolitis (typical relative risk 1.02 (95% confidence interval 0.79 to 1.33); typical risk difference 0.00 (95% confidence interval -0.02 to 0.03)), days to full enteral nutrition (weighted mean difference -1.1 days (95% confidence interval -3.4 to 1.2)), or duration of hospital stay (weighted mean difference 0.65 days (95% confidence interval -2.9 to 4.2)).

The available data from good quality randomised controlled trials suggest that glutamine supplementation does not confer clinically significant benefits for preterm infants. The narrow confidence intervals for the effect size estimates suggest that a further trial of this intervention is not a research priority.