Elsevier

Current Paediatrics

Volume 13, Issue 3, June 2003, Pages 184-189
Current Paediatrics

The prevention and management of necrotizing enterocolitis

https://doi.org/10.1016/S0957-5839(03)00025-3Get rights and content

Abstract

Necrotizing enterocolitis remains a devastating illness and there is some evidence that mortality from it is increasing. Although there has been little change in the management of established necrotizing enterocolitis, studies based on known risk factors are leading to possible preventive strategies. Several of these are based on the knowledge that breast milk is partially protective. Nutritional approaches may involve arginine, erythropoietin and epidermal growth factor supplementation. Other strategies may include manipulating the bacterial milieu of the bowel and influencing the inflammatory cascade.

Introduction

Although necrotizing enterocolitis (NEC) remains a devastating condition, there do appear to be new approaches that may well impact on its prevalence, severity and management. Many of these advances seem to have occurred in response to the question, ‘why is breast milk protective’?

Section snippets

Prevalence and cost

Data on prevalence are difficult to obtain, primarily because of a variation in the classification of ‘mild’ cases (stage 1 of the Bell classification). Between October 1993 and October 1994, the British Paediatric Surveillance Unit (for England, Wales, Scotland and Ireland) survey of NEC found 185 cases of definite NEC grade 2 (intramural/portal gas or diagnosis confirmed at laparotomy or post mortem), with 115 suspected to be grade 1, thus giving an incidence of confirmed NEC as 0.23 cases

Erythropoietin

Breast milk contains a large quantity of erythropoietin, in an amount not dissimilar to that used to treat anaemia of prematurity. Erythropoietin receptors are present on the preterm enterocyte, and rat enterocytes exposed to erythropoietin migrate more quickly, this being a marker of improved mucosal integrity. Erythropoietin also appears to be resistant to digestion and, when added to formula feeds, can be used to stimulate erythropoesis.4 In a retrospective non-randomized study of 483

Arginine

Endothelial nitric oxide, a potent local vasodilator, may be important in maintaining mucosal integrity. The inhibition of nitric oxide synthetase (NOS) has been shown to potentiate the severity of NEC-like lesions in experimental models; conversely, enhanced NOS activity may be protective. Arginine is the amino acid with the richest source of nitrogen and is a precursor for the formation of glutamine and glutamate, nitric oxide being synthesized from arginine by NOS. Several studies have shown

Epidermal Growth Factor

Epidermal growth factor (EGF), a heat-stable 53 amino acid peptide, is present in large amounts in amniotic fluid and breast milk. It has a marked trophic effect on the gastrointestinal tract, with enhanced proliferation and differentiation of the epithelial cells. Sullivan et al. demonstrated in an 8-month-old infant with nectrotising enteritis that intravenous EGF improved the crypt cell proliferative activity and recovery of the surface epithelium.8 Its action appears to occur through

Bacterial colonization prebiotics and probiotics

NEC is not seen in utero and is unusual in the infant who has not been enterally fed, suggesting that both bacterial colonization of the gut and luminal contents are important. Lucas, and recently Schanler et al.,11 have reported the protective effect of breast milk.

Two recent studies have looked at upper gastrointestinal colonization in preterm infants. In a unit in which they gastrically gravity-fed their infants 4-hourly, Mehall12 looked at the colonization rate of their nasogastric tubes,

Splanchnic blood flow velocities

Interest in splanchnic Doppler flow was partly triggered by the observations of the association between absent or reversed end-diastolic flow in the umbilical artery and the development of NEC. Although Doppler ultrasound has proved to be a useful tool for measuring blood flow velocity in the superior mesenteric artery and celiac axis, it has not proved to be an easy tool for the long-term monitoring of splanchnic perfusion.

Robel-Tillig et al.18 provide further data on the outcome of fetuses

Enteral antibiotics and immunoglobulin

The Cochrane Library has recently reviewed these two areas.19., 20. There have been five eligible trials of enteral antibiotics involving 456 infants, four early studies using gentamicin or kananycin, the latest employing vancomycin started on day 2 for 7 days.21 Overall, there was a reduction in the incidence of NEC (RR 0.47, 95% CI 0.28–0.78) and NEC deaths (RR 0.32, 95% CI 0.10–0.96) but not overall deaths (RR 0.67, 95% CI 0.34–1.32). Siu et al.21 found no evidence of vancomycin resistance, but

Platelet activating factor

Many models of NEC propose that there is a final common pathway linking the proposed risk factors with the development of ischaemic necrosis. One of the proposed mediators is platelet activation factor (PAF), one member of a family of phospholipids synthesized by many cell types, including enterocytes. It usually acts at a local level and has a short half-life. Breast milk contains PAF acetylhydrolase, a PAF degrading enzyme. Ewer22 has studied the effect of endogenous PAF in a neonatal pig

Surgical management

The criteria for surgery and the choice of procedure for NEC vary greatly between units. Over the past 20 years, the option of percutaneous peritoneal drainage as opposed to primary laparotomy has become more widespread for intestinal perforation, especially in infants weighing less than 1000 g. The long-term benefit of this approach is not, however, clear. It is undoubtedly a more straightforward procedure than laparotomy, although not without its own risks (Fig. 1).

Moss et al.,23 in a review

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