Arginine supplementation for prevention of necrotising enterocolitis in preterm infants

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Abstract
Background Decreased concentration of nitric oxide is proposed as one of the possible cellular mechanisms for necrotising enterocolitis (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 methods A literature search was performed using the following databases: MEDLINE (1966 to April 2007), EMBASE (1980 to April 2007), CINAHL (1982 to 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 to 2007). No language restrictions were applied. The electronic search was updated in August 2010. Selection criteria Randomised or quasi‐randomised controlled trials of arginine supplementation (administered orally or parenterally for at least seven days in addition to what an infant may be receiving from enteral or parenteral source) compared to placebo or no treatment. 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 to 0.61); RD ‐0.21 (95% CI ‐0.32 to ‐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 randomised controlled study of arginine supplementation in preterm neonates is needed, focusing on the incidence of NEC, particularly the more severe stages (2 or 3).