Current research in necrotizing enterocolitis
Introduction
Although necrotizing enterocolitis (NEC) is one of the most common life-threatening surgical diseases affecting neonates, we still do not completely understand the pathogenesis or how to prevent or treat the disease [1]. The high mortality (around 30% for surgical NEC [2], [3] and long-term morbidity [4, 5] of survivors mandates urgent research into the pathogenesis, diagnosis, prevention and treatment of this devastating disease. There are several animal models of NEC, however, it is not completely clear how accurately these models recapitulate the human disease. This is particularly difficult as clinical NEC itself is quite variable, with some authors arguing for sub-classification into different forms reflecting the differences in disease onset and progression between a ‘typical’ NEC presentation in an extremely premature infant who has been fed enterally for a few weeks, and other presentations such as NEC in a term infant who has a cardiac defect or who has had gastroschisis [6]. As a consequence of the limitations of the animal models, it is vital to undertake clinical research studies in parallel with basic science/animal model studies, and in this brief review article, our aim is to describe some areas of current research interest; an exhaustive review of all current NEC research is unfeasible.
Section snippets
Pathogenesis
The main factors thought to be involved in the pathogenesis of NEC are: intestinal immaturity, enteral feeds, the intestinal microbiome, inflammation and local ischaemia and/or reperfusion injury. We will briefly discuss recent research in each of these areas below.
Diagnosis
Diagnosis of NEC currently relies on a combination of clinical symptoms and signs, and radiological features such as pneumatosis intestinalis and pneumoperitoneum, which are encapsulated in the Bell's stages of disease, which although frequently criticized, are still widely used to describe populations of infants with NEC. For many years, researchers have sought biomarkers that would be diagnostic for NEC in plasma, urine or stool samples (reviewed [57], [58]). One of the most widely researched
Dietary/pharmacological approaches
There are several suggested dietary and/or pharmacological approaches to the prevention of NEC. Many of these agents are found in human breast milk, for example lactoferrin is a glycoprotein that forms part of the innate immune response. It is found in high concentration in colostrum and lower concentration in breast milk and has antibacterial and antiviral properties. It has been speculated that it would be a potential preventative measure for NEC, but few animal or human studies have yet been
Conclusions
Despite understanding the cardinal features involved in the pathogenesis of NEC, and decades of research, we still do not fully understand this devastating disease, how to prevent it or treat it. Nevertheless, the broad range and depth of research on the topic does lead to a degree of optimism that clinicians and scientists will hopefully be able to deliver novel preventative, diagnostic and therapeutic strategies that will translate into improved outcomes.
Research directions
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Testing of research-based biomarkers in large clinical cohorts to determine whether they improve decision-making
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Improve understanding of the interplay between microbiota and intestinal inflammation
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Elucidation of the molecular basis of the protective effect of probiotics, in order to optimise probiotic strains to be used in prevention of NEC
Conflict of interest statement
Simon Eaton has received consultancy fees from Fresenius Kabi and a speaker's honorarium from Danone. The authors have no other relevant financial interests or affiliations.
Acknowledgements
SE gratefully acknowledges support from Great Ormond Street Hospital Children's Charity and NJH is supported by the NIHR Southampton Biomedical Research Centre in Nutrition.
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