Noninvasive Biomarkers of Necrotizing Enterocolitis

Abstract

Necrotizing enterocolitis is an acute inflammatory disease, which primarily affects preterm infants, and is a leading cause of morbidity and mortality in the neonatal intensive care unit. Unfortunately, necrotizing enterocolitis can be difficult to distinguish from other diseases and clinical conditions especially during the early course of the disease. This diagnostic uncertainty is particularly relevant to clinical evaluation and medical management and potentially leads to unnecessary and extended periods of cessation of enteral feedings and prolonged courses of parenteral nutrition and antibiotics. Biomarkers are molecular indicators of a disease process, diagnosis, prognosis and can be used to monitor the effects of disease management. Historically, there has been a paucity of reliable and robust biomarkers for necrotizing enterocolitis. However, several studies have recently identified promising biomarkers. Noninvasive samples for biomarker measurement are preferred and may have certain advantages in the preterm infant. In this review article, we focus on recent exciting and promising discoveries in noninvasive biomarkers for necrotizing enterocolitis.

Necrotizing enterocolitis: new insights into pathogenesis and mechanisms

“…In this regard, the presence of several molecules that are detected in the blood have been assessed for their value in establishing the diagnosis of NEC 43–45 and a number of them have shown considerable promise, including acute-phase reactants (such as C-reactive protein) and proinflammatory cytokines (for example, TNFα, IL-6 and IL-8) 45 . In addition, organ-specific biomarkers, such as those that would indicate enterocyte injury or intestinal barrier impairment, include intestinal fatty acid-binding protein, liver fatty acid-binding protein, faecal calprotectin, trefoil factor 3 and claudin-3 (REFS 41,46 ).…”

Necrotizing enterocolitis

“…I‐FABP is found in enterocytes and localized mainly in the villi of the small intestine. Enterocyte damage causes release of I‐FABP into the circulation, and blood and urine levels of I‐FABP are increased with intestinal injury and NEC . It is unlikely that a single biomarker will possess the requisite sensitivity and specific profiles required for adequate diagnostic accuracy and a composite of two or more markers together may provide improved diagnostic accuracy.…”

“…For example, urine I‐FABP combined with fecal calprotectin, a cytoplasmic protein released by activated neutrophils and monocyte‐macrophages, and urine serum amyloid A, an acute phase reactant protein, improved diagnostic accuracy as compared to I‐FABP alone . Therefore, a comprehensive proteomic and/or metabolomic approach may ultimately be more advantageous to evaluate and define NEC (Nantais‐Smith 2015) . Intestinal microbiome assessment can also help evaluate bacterial populations specific to NEC and has the potential to aid in diagnosis …”

“…15 Much recent work has focused on specific biomarkers for prediction, early diagnosis, and determination of disease severity. 8,16 Various specific proteins, including cytokines, measured in blood, urine, and stool, have been evaluated, but most have poor specificity for making an accurate diagnosis. 17 However, blood inter-alpha inhibitor proteins are able to distinguish NEC from SIP and NEC from matched controls with feeding intolerance.…”

New Frontiers of Necrotizing Enterocolitis: From Pathophysiology to Treatment

“…In this regard, the presence of several molecules that are detected in the blood have been assessed for their value in establishing the diagnosis of NEC and a number of them have shown considerable promise, including acute-phase reactants [such as C-reactive protein] and proinflammatory cytokines [for example, TNFα, IL-6 and IL-8] which were found as nonspecific [55] [56] [57].…”