Abstract

Necrotizing Enterocolitis (NEC) is most common gastrointestinal infection in predominantly preterm neonates. It needs multifaceted approach for the treatment and prevention. The first case of nectrotizing enterocolitis was reported in 1823. But till now there is hardly any definite treatment in advanced stages, prevention has the main role in this disease. In NEC, the intestinal mucosa actually excoriates, becomes totally necrosed soggy and dies off. What is the actual cause of this death and why it is more prevalent in preterm, is not fully clear. Some of the recent research has thrown some lights on it. There is a great role of Toll like receptor 4 (TLR-4) for the pathogenesis. These receptors identify the pathogen (The bacterial cell wall lipo-polysaccharides-LPS) and stimulate the host to react to it, induce a pro inflammatory reaction. This activates cytokine inducing transcription factor NFkB. This TLR4 signal induces endoplasmic reticulum and enterocyte apoptosis along with reduction of mucosal repair. This results in mucosal breakdown and bacterial migration and sepsis. This TLR4 expression specifically occurs on the intestinal progenitor cells within the crypts. This TLR4 expression is higher in preterm newborn than in full term. Breast milk is a strong TLR4 signaling inhibitor. It is well enriched with NO precursor molecule and human milk oligosaccharides, which increase intestinal wall perfusion, prevent an exaggerated reaction to bacterial cell wall and NEC. Amniotic fluid also have protective role through higher concentration of epidermal growth factor which is an inhibitor of TLR4 signaling. Probiotic bacterial DNA also can inhibit the TLR4 signaling. Disruption of gut microbiota and its homeostasis is also an important factor for NEC development. Intestinal epithelium cell regeneration also gets hampered in NEC. Normally it renews every 3-6 days, it is driven by the vigorous proliferation of epithelium within the crypts towards the villous tip. In the crypts there is a specific stem cell zone called Intestinal stem cell (ISC), whose population is reduced in NEC. The diagnosis of NEC is also not very easy and there is lot of scope for further advancement. Main conventional methods of diagnosis are clinical surveillance, abdominal radiograph, blood count, stool occult blood detection, comprehensive metabolic panel. Recently different biomarkers are getting explored. Increased fecal calprotectin, microbial composition of stool, fecal volatile organic compounds, level of urine I-FABP (Intestinal fatty acid binding protein), Urinary SAA (serum amyloid A), Prostaglandin E2 major urinary metabolite, Urinary protein gets increased in NEC. Serum I-FABP, Ischemia modified albumin (IMA), Interleukin -8(IL-8), acylcarnitine level gets increased, Fibrinogen γ dimmers, Inter α inhibitor protein, decreases in NEC. Among the other non invasive markers those predict NEC are near infrared spectroscopy, Doppler flow velocity of superior mesenteric artery, heart rate variability, decreased vagal tone, gene polymorphism. Recent advancement of the treatment strategies are breast milk component, prophylactic pre, pro biotics and stem cell administration. But prevention is the best strategy like avoiding premature delivery, slow progress of oral feed, avoiding formula feed.