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Arginine supplementation for prevention of necrotising enterocolitis in preterm infants

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Abstract

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

This review examines the efficacy and safety of arginine supplementation in decreasing the incidence of NEC among preterm neonates.

Search methods

A literature search was performed using the following databases: MEDLINE (1966 ‐ June 2004), EMBASE (1980 ‐ June 2004), CINAHL (1982 ‐ June 2004), Cochrane Controlled Trials Register (Issue 2, 2004 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 (1991‐2004). No language restrictions were applied.

Selection criteria

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 7 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.

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 stage 2 or 3.

PICOs

Population
Intervention
Comparison
Outcome

The PICO model is widely used and taught in evidence-based health care as a strategy for formulating questions and search strategies and for characterizing clinical studies or meta-analyses. PICO stands for four different potential components of a clinical question: Patient, Population or Problem; Intervention; Comparison; Outcome.

See more on using PICO in the Cochrane Handbook.

Plain language summary

Synopsis pending.