Necrotizing enterocolitis: Pathophysiology from a historical context

Abstract

Necrotizing Enterocolitis (NEC) continues to afflict approximately 7% of preterm infants born weighing less than 1500 grams, though recent investigations have provided novel insights into the pathogenesis of this complex disease1. The disease has been a major cause of morbidity and mortality in neonatal intensive care units worldwide for many years, and our current understanding reflects exceptional observations made decades ago. In this review, we will describe NEC from a historical context and summarize seminal findings that underscore the importance of enteral feeding, the gut microbiota, and intestinal inflammation in this complex pathophysiology.

Necrotizing Enterocolitis, Gut Microbiota, and Brain Development: Role of the Brain-Gut Axis

“…Preterm infants who survive NEC are at increased risk of neurocognitive deficits. Although the exact etiology of NEC has not been elucidated, microbiota play a major role in its development by inciting a TLR4-mediated inflammatory cascade [41]. …”

“…First, in TLR mutant or knockout animals, NEC is not inducible. Second, probiotic bacteria that activate TLR9, which in turn limits the degree of TLR4 signaling, are associated with reduced NEC in clinical studies [38, 41, 42]. …”

Necrotizing Enterocolitis: Using Regulatory Science and Drug Development to Improve Outcomes

“…Although clinical associations (eg, enteral feeding, blood transfusion), predisposing risk factors (eg, prematurity, altered intestinal microbiome, growth restriction), and specific molecular pathway involvement (eg, Toll-like receptor-4 signaling) are well established, the interactions between each of these factors and exposures are not fully understood. 2,3 There are currently no licensed drugs or biologics for the prevention and/or treatment of NEC.…”

Neonatal Necrotizing Enterocolitis - Diagnostic Problems

“…Наявні дані досліджень показують різну частоту НЕК (в середньому -10% недоношених з ДММТ); але більшість результатів демонструють стабільність показників. Частка тих, хто потребує хірургічного втручання становить 27-52% [1,[21][22][23][24][26][27][28][29][30].…”

“…Узагальнення інформації призвело до визнання того, що різні групи новонароджених мають відмінні фактори ризику НЕК, різну ефективність діагностичних алгоритмів, превентивних і лікувальних технологій, і, нарешті, до визнання існування «підмножини НЕК» [1,[21][22][23][24][26][27][28][29][30].…”