Arginine supplementation for prevention of necrotising enterocolitis in preterm infants

Shah PS, Shah VS

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Summary

Arginine supplementation for prevention of necrotising enterocolitis in preterm infants

Arginine supplements for preventing severe, damaging inflammation of the gastrointestinal (GI) tract (necrotising enterocolitis) in infants born before 37 weeks gestation (preterm). Necrotising enterocolitis (NEC) may be caused by an infant's immaturity, a lack of blood flow to the GI tract (ischemia), and surface (mucosa) breakdown resulting from infection or feeding with strong/concentrated (hyperosmolar) solutions. It can result in feeding intolerance, problems with intestinal motility or a very sick infant. To protect the GI tract the body makes a natural substance, nitric oxide, from the amino acid arginine. Plasma arginine concentrations are reported to be low in very low birth weight infants and preterm infants who develop NEC. Adding extra arginine to the feeding solution may, therefore, prevent NEC. The review authors searched the literature for controlled studies evaluating the efficacy and safety of arginine supplementation. Adding extra arginine to a preterm infant's feed, starting between 2 to 5 days of age and continued until 28 days of age, reduced the risk of developing NEC in one good quality study (in 152 infants born at less than 32 weeks gestation). Five infants had to be treated for one to benefit. This was the only study identified and it had a high incidence of NEC possibly because it included even the lowest grade of NEC. No significant side effects directly attributable to too much arginine were observed. Possible effects of supplementing arginine are a lowering of blood pressure and change in control of blood glucose.

This is a Cochrane review abstract and plain language summary, prepared and maintained by The Cochrane Collaboration, currently published in The Cochrane Database of Systematic Reviews 2010 Issue 1, Copyright © 2010 The Cochrane Collaboration. Published by John Wiley and Sons, Ltd.. The full text of the review is available in The Cochrane Library (ISSN 1464-780X).
This record should be cited as: Shah PS, Shah VS. Arginine supplementation for prevention of necrotising enterocolitis in preterm infants. Cochrane Database of Systematic Reviews 2007, Issue 3. Art. No.: CD004339. DOI: 10.1002/14651858.CD004339.pub3.

This version first published online: October 18. 2004
Last assessed as up-to-date: May 01. 2007

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

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.

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 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).

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