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 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.

Glutamine supplementation for prevention of morbidity in preterm infants.

BACKGROUND: The amino acid glutamine is the preferred respiratory fuel for rapidly proliferating cells under normal conditions. Recent research has suggested a number of roles for glutamine during critical illness. This research has been largely performed in experimental animals and in adults in a variety of disease settings. There is little information on the role of glutamine in children and infants, or whether glutamine supplementation is beneficial in preterm babies. OBJECTIVES: To determine the effects of glutamine supplementation on morbidity and weight gain in preterm babies. SEARCH STRATEGY: Searches were made using the Cochrane Controlled Trials Register, Medline and Embase electronic databases from 1980 - June 2001 (MeSH terms: glutamine, preterm, newborn, nutrition), handsearching of selected English language journals (Pediatrics, Journal of Pediatrics, Archives of Disease in Childhood and Journal of Pediatric Gastroenterology and Nutrition) from 1990 - June 2001, and cross-referencing from publications where necessary. SELECTION CRITERIA: Randomised controlled trials comparing glutamine supplementation to no glutamine supplementation in preterm babies at any time from birth to discharge from hospital. DATA COLLECTION AND ANALYSIS: Data regarding clinical outcomes including duration of parenteral nutrition, time to full enteral nutrition, rate of weight gain, rate of positive blood cultures and duration of hospital stay were extracted by both reviewers. Analysis was performed by the primary reviewer (TRJT) in accordance with the standards of the Cochrane Neonatal Review Group. MAIN RESULTS: Three trials met the selection criteria. Data on proportion of babies having one or more of positive blood cultures were available from all three studies. Meta-analysis showed no significant difference between glutamine-supplemented and non-supplemented babies; RR = 0.73 (95% CI 0.44, 1.23), RD = -8.8% (95% CI -23.2, 5.5). Data for other outcome variables were pooled from two studies. There were no significant differences between glutamine-supplemented and non-supplemented babies for days to full enteral nutrition (WMD 0.4 days, 95% CI -3.0, 3.8), rate of weight gain (WMD 0.6 g/kg/d, 95% CI -1.6, 2.8) or days of hospital stay (WMD -2.4 days, 95% CI -14.9, 10.2). REVIEWER'S CONCLUSIONS: There is no evidence from randomised trials to support the routine use of parenteral or enteral glutamine supplementation in preterm babies. A large randomised controlled trial should be performed to determine whether or not glutamine supplementation enhances gut integrity and reduces sepsis rate.

Glutamine supplementation for preventing morbidity in preterm infants.

BACKGROUND: The amino acid glutamine is the preferred respiratory fuel for rapidly proliferating cells under normal conditions. Recent research has suggested a number of roles for glutamine during critical illness. This research has been largely performed in experimental animals and in adults in a variety of disease settings. There is little information on the role of glutamine in children and infants, or whether glutamine supplementation is beneficial in preterm babies. OBJECTIVES: To determine the effects of glutamine supplementation on morbidity and weight gain in preterm babies. SEARCH STRATEGY: Searches were made using Medline and Embase electronic databases and specific handsearching in the English language. The search strategy followed the guidelines of the Neonatal Cochrane Review Group. SELECTION CRITERIA: Randomised controlled trials comparing glutamine supplementation to no glutamine supplementation in preterm babies at any time from birth to discharge from hospital. DATA COLLECTION AND ANALYSIS: Data regarding clinical outcomes including duration of parenteral nutrition, time to full enteral nutrition, rate of weight gain, rate of positive blood cultures and duration of hospital stay were extracted by both reviewers. Analysis was performed by the primary reviewer (TRJT) in accordance with the standards of the Cochrane Neonatal Review Group. MAIN RESULTS: Three trials met the selection criteria. Data on proportion of babies having one or more of positive blood cultures were available from all three studies. Meta-analysis showed no significant difference between glutamine-supplemented and non-supplemented babies; RR = 0.73 (95% CI 0.44, 1.23), RD = -8.8% (95% CI -23.2, 5.5). Data for other outcome variables were pooled from two studies. There were no significant differences between glutamine-supplemented and non-supplemented babies for days to full enteral nutrition (WMD 0.42, 95% CI -3.0, 3.8), rate of weight gain (WMD 0.6 g/kg/d, 95% CI -1.6, 2.8) or days of hospital stay (WMD -2.4, 95% CI -14.9, 10.2). REVIEWER'S CONCLUSIONS: There is no evidence to support the routine use of parenteral or enteral glutamine supplementation in preterm babies. A large randomised controlled trial should be performed to determine whether or not glutamine supplementation enhances gut integrity and reduces sepsis rate.

A subchronic toxicity study of octyl acetate in rats.

The subchronic toxicity of octyl acetate was assessed following its administration to rats via oral gavage, 5 days per week for 13 weeks. Treated rats received undiluted octyl acetate at doses of 0.1, 0.5, or 1.0 g/kg. Control rats received distilled water at a dose of 1.0 g/kg. An interim termination was made after 45 days of dosing at which time five animals per sex per group were terminated and necropsied. Blood samples were collected and liver tissues were prepared for histological examination. After 13 weeks of dosing all animals were terminated and necropsied. Blood samples were obtained and selected organs were weighed and prepared for subsequent histological examination. Several treatment-related effects were observed in the high-dose group (1.0 g/kg) animals. These effects included slight reductions in body weight and food consumption, increased liver and kidney weights, and evidence of hydrocarbon nephropathy in high-dose males only. The significance of these observations is discussed in the report. With the exception of increased liver weights in the mid-dose group, no other significant treatment-related effects were observed in the mid- or low-dose groups of animals. It is believed that the increases in liver weight which were observed are a compensatory response to an increased metabolic load, and not a reflection of true hepatotoxicity. The results of this study indicated that octyl acetate possessed an overall low degree of systemic toxicity when administered orally to rats for 13 weeks.