Background: Immaturity, ischemia, and disturbances in gut mucosal integrity due to infections or hyperosmolar feeds are some of the suspected mechanisms in the development of necrotising enterocolitis (NEC) in preterm infants. Decreased concentration of nitric oxide is proposed as one of the possible cellular mechanisms for NEC. Plasma arginine concentrations were found to be lower in infants who developed NEC. Arginine can act as a substrate for the production of nitric oxide in the tissues and arginine supplementation may help in preventing NEC.
Objectives: To examine the effect of arginine supplementation on the incidence of NEC in preterm neonates.
Search strategy: A literature search was performed using the following databases: MEDLINE (1966 - April 2007), EMBASE (1980 - April 2007), CINAHL (1982 - April 2007), Cochrane Controlled Trials Register (Issue 2, 2007 of Cochrane Library) and abstracts from the annual meetings of the Society for Pediatric Research, American Pediatric Society and Pediatric Academic Societies published in Pediatric Research (1991-2007). No language restrictions were applied.
Study design: randomized or quasi-randomized controlled trials.
Population: preterm neonates.
Intervention: enteral or parenteral arginine supplementation (in addition to what an infant may be receiving from enteral or parenteral source), compared to placebo or no treatment; arginine administered orally or parenterally for at least seven days in order to achieve adequate plasma arginine levels (145 umol/l).
Outcomes: any of the following outcomes - NEC, death prior to discharge, death due to NEC, surgery for NEC, duration of total parenteral nutrition, plasma concentrations of arginine and glutamine at baseline and seven days after intervention, side effects of arginine.
Data collection and analysis: The methodological quality of the trials was assessed using the information provided in the studies and by personal communication with the author. Data on relevant outcomes were extracted and the effect size was estimated and reported as relative risk (RR), risk difference (RD) and mean difference (MD) as appropriate.
Main results: Only one eligible study was identified. The methodological quality of the included study was good. There was a statistically significant reduction in the risk of developing NEC (any stage) in the arginine group compared with the placebo group [RR 0.24 (95% CI 0.10, 0.61), RD -0.21 (95% CI -0.32, -0.09)]. No significant side effects directly attributable to arginine were observed. In this updated version, follow up data from this trial were available that revealed no statistically significant difference in the adverse outcomes.
Authors' conclusions: The data are insufficient at present to support a practice recommendation. A multicentre randomized controlled study of arginine supplementation in preterm neonates is needed, focusing on the incidence of NEC, particularly the more severe stages (2 or 3).