Glutamine supplementation to prevent morbidity and mortality in preterm infants.

BACKGROUND: 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. OBJECTIVES: To determine the effects of glutamine supplementation on mortality and morbidity in preterm infants. SEARCH STRATEGY: The standard search strategy of the Cochrane Neonatal Review Group was used. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2007), MEDLINE (1966 - July 2007), EMBASE (1980 - July 2007), conference proceedings, and previous reviews. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials that compared glutamine supplementation versus no glutamine supplementation in preterm infants at any time from birth to discharge from hospital. DATA COLLECTION AND ANALYSIS: The standard methods of the Cochrane Neonatal Review Group were used, with separate evaluation of trial quality and data extraction by two authors. Data were synthesised using a fixed effects model and reported using typical relative risk, typical risk difference and weighted mean difference. MAIN RESULTS: 2365 preterm infants have participated in seven randomised controlled trials. All of the participating infants were of very low birth weight. Three trials assessed enteral glutamine supplementation and four trials assessed parenteral glutamine supplementation. The trials were generally of good methodological quality with adequate allocation concealment, blinding of caregivers and assessors to the intervention, and complete or near-complete follow-up of recruited infants. Glutamine supplementation does not have a statistically significant effect on mortality: typical relative risk 0.98 (95% confidence interval 0.80 to 1.20); typical risk difference 0.00 (95% confidence interval -0.03 to 0.02). The only trial that assessed long-term outcomes did not find any statistically significant differences in various assessments of neurodevelopment at 18 months corrected age. Glutamine supplementation does not have a statistically significant effect on other neonatal morbidities including invasive infection, necrotising enterocolitis, time to achieve full enteral nutrition, or duration of hospital stay. AUTHORS' CONCLUSIONS: The available data from good quality randomised controlled trials indicate that glutamine supplementation does not confer 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.

Glutamine supplementation to prevent morbidity and mortality in preterm infants.

BACKGROUND: 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. OBJECTIVES: To determine the effects of glutamine supplementation on mortality and morbidity in preterm infants. SEARCH STRATEGY: 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. SELECTION CRITERIA: 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. DATA COLLECTION AND ANALYSIS: 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. MAIN RESULTS: 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)). AUTHORS' CONCLUSIONS: 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.

A comparison of lutein and zeaxanthin concentrations in formula and human milk samples from Northern Ireland mothers.

BACKGROUND: Two carotenoids, lutein and zeaxanthin are found in the retinal pigment epithelium of the eye where they are believed to protect it against oxidative and light damage. The amounts of these carotenoids consumed by premature infants are not known. OBJECTIVE: The objective of the investigation was to measure these carotenoids in human and formulae milks. DESIGN: In all, 28 human milk samples were obtained at various times between days 1 and 41 of lactation from 13 mothers. Six formula milks commonly used in hospitals were also analysed. SETTING: Mothers who provided the milk samples had infants in the neonatal ward at the Royal Maternity Hospital, Belfast. RESULTS: Median lutein and zeaxanthin concentrations in human milk were 4.79 (range 0.42-9.98) nmol/g fat and 0.55 (0.00-1.70) nmol/g fat, respectively. Five of the six formula milks also contained lutein and zeaxanthin with concentrations that varied over a wide range (0.7-9.7 and 0.1-1.2 nmol/g fat, respectively). CONCLUSIONS: Carotenoid concentrations usually decreased with the duration of lactation. Some formula milks that were specially formulated for premature infants contained high concentrations of the lutein and zeaxanthin and the source may be egg yolk. SPONSORSHIP: These studies were supported by the University of Ulster and the Northern Ireland Mother and Baby Appeal.

A randomized, controlled trial of parenteral glutamine in ill, very low birth-weight neonates.

OBJECTIVE: The role of "novel substrates" in neonatal nutrition has generated much interest in recent years. Glutamine has been recognized as a "conditionally essential" amino acid in critically ill adults, particularly for gut and immune function; however, its potential role in the neonate remains unclear. The authors examined the safety and benefits of parenteral glutamine in ill, preterm neonates. DESIGN: Randomized controlled trial. METHODS: Thirty-five ill preterm neonates of <1000 g birth-weight were randomized to receive either glutamine-supplemented parenteral nutrition (PN) (n = 17) or standard PN (n = 18). RESULTS: There were no significant differences in birth-weight, gestational age, male-to-female ratio, or Clinical Risk Index for Babies (CRIB) score between the two groups. During PN there were no significant differences between the groups in white cell count, differential white cell count, blood urea nitrogen, plasma ammonia, lactate, pyruvate, plasma glutamine, or glutamate. The median time to achieving full enteral nutrition (FEN) was shorter in the study group (13 days vs. 21 days, P < 0.05). The number of episodes of culture-positive sepsis or age at discharge did not differ between groups. CONCLUSIONS: Parenteral glutamine appears to be well tolerated and safe in the ill, preterm neonate. It may reduce the time to achieving FEN.