Necrotizing Enterocolitis

Dominguez, Kathleen M.; Moss, Richard L.

doi:10.1016/j.clp.2012.04.011

Cited by 73 publications

(59 citation statements)

References 82 publications

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“…The defining pathological feature of NEC is the presence of patchy areas of ischemia and necrosis of the small and large intestine (2). Although prematurity is the leading risk factor for NEC development, breast milk administration has been identified as the most important protective strategy (3).…”

mentioning

confidence: 99%

Endothelial TLR4 activation impairs intestinal microcirculatory perfusion in necrotizing enterocolitis via eNOS–NO–nitrite signaling

Yazji

Sodhi²,

Lee³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

202

171

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Necrotizing enterocolitis (NEC) is a devastating disease of premature infants characterized by severe intestinal necrosis and for which breast milk represents the most effective protective strategy. Previous studies have revealed a critical role for the lipopolysaccharide receptor toll-like receptor 4 (TLR4) in NEC development through its induction of mucosal injury, yet the reasons for which intestinal ischemia in NEC occurs in the first place remain unknown. We hypothesize that TLR4 signaling within the endothelium plays an essential role in NEC development by regulating perfusion to the small intestine via the vasodilatory molecule endothelial nitric oxide synthase (eNOS). Using a unique mouse system in which we selectively deleted TLR4 from the endothelium, we now show that endothelial TLR4 activation is required for NEC development and that endothelial TLR4 activation impairs intestinal perfusion without effects on other organs and reduces eNOS expression via activation of myeloid differentiation primary response gene 88. NEC severity was significantly increased in eNOS −/− mice and decreased upon administration of the phosphodiesterase inhibitor sildenafil, which augments eNOS function. Strikingly, compared with formula, human and mouse breast milk were enriched in sodium nitrate-a precursor for enteral generation of nitrite and nitric oxide-and repletion of formula with sodium nitrate/nitrite restored intestinal perfusion, reversed the deleterious effects of endothelial TLR4 signaling, and reduced NEC severity. These data identify that endothelial TLR4 critically regulates intestinal perfusion leading to NEC and reveal that the protective properties of breast milk involve enhanced intestinal microcirculatory integrity via augmentation of nitrate-nitrite-NO signaling.neonatal inflammation | prematurity | infant formula | neonatal nutrition | sepsis N ecrotizing enterocolitis (NEC) is the leading cause of death from gastrointestinal disease in the premature infant and is gradually increasing in frequency (1). The defining pathological feature of NEC is the presence of patchy areas of ischemia and necrosis of the small and large intestine (2). Although prematurity is the leading risk factor for NEC development, breast milk administration has been identified as the most important protective strategy (3). Importantly, the mechanisms that lead to the acute development of intestinal necrosis in the premature intestine and factors within breast milk that may prevent NEC remain largely unexplored.In seeking to understand the underlying biological mechanisms that lead to NEC, we and others have identified a critical role for the innate immune receptor toll-like receptor 4 (TLR4) in NEC pathogenesis, because mice deficient in TLR4 showed reduced mucosal inflammation and reduced intestinal necrosis in experimental NEC (4, 5). Microcirculatory perfusion of the premature intestine is primarily regulated by the vasodilator nitric oxide (NO), which is generated through the activity of endothelial NO synthase (eNOS) (6). ...

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mentioning

confidence: 99%

Endothelial TLR4 activation impairs intestinal microcirculatory perfusion in necrotizing enterocolitis via eNOS–NO–nitrite signaling

Yazji

Sodhi²,

Lee³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

202

171

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“…Perforated NEC is a mandatory indication for surgical treatment 9 ; however, the specific approach is guided by the infant's characteristics and clinical conditions. In the present case, repeated attempts to manage intestinal perforation by placing a PD were unsuccessful.…”

Section: Discussionmentioning

confidence: 99%

“…Such a prolonged course was aimed at avoiding the occurrence of EFs, which are a wellknown complication of abdominal surgery on which octreotide is shown to be effective. 9 Furthermore, the dosage was tapered slowly to prevent possible rebound effects. 17 At present, data about the optimal neonatal dosage of octreotide are scarce.…”

Section: Discussionmentioning

confidence: 99%

Octreotide in a Critically Ill Extremely Preterm Infant With Perforated Necrotizing Enterocolitis

et al. 2016

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Necrotizing enterocolitis (NEC) is the most severe gastrointestinal complication of prematurity. Surgery, either peritoneal drainage placement or laparotomy with resection of the intestinal necrotic tracts, is the definitive treatment of perforated NEC; however, when clinical conditions contraindicate surgical approaches, little is known about medical treatments adjuvant or alternative to surgery. Octreotide is a synthetic somatostatin analog that inhibits pancreatic secretion and leads to splanchnic vasoconstriction. In preterm neonates, it is mainly used off-label for chylothorax and congenital hyperinsulinism, whereas gastrointestinal indications are limited. We describe the case of a critically ill extremely low birth weight infant with perforated NEC, who had unsuccessfully undergone peritoneal drainage placement and laparotomy. Her unstable condition contraindicated a further laparotomy, thus off-label treatment with octreotide was attempted. No adverse events occurred. The infant’s condition gradually improved and progressive reduction of peritoneal outputs and successful resolution of pneumoperitoneum were achieved, with no relapse after octreotide discontinuation.

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“…NEC is an inflammatory process, characterized by intestinal necrosis of variable extension, leading to perforation, generalized peritonitis and death (1,4). It is the most common gastrointestinal emergency in the newborn (1)(2)(3)5,6), more frequent in the preterm infant, especially those of very low weight [newborns with birth weight <1,500 g or very low birth weight (VLBW)], although it affects term infants also (5,(7)(8)(9)(10). The incidence of NEC in VLBW infants, stable over the years, is between 5-7% (11,12); a slight increase over the period [2000][2001][2002][2003][2004][2005][2006][2007][2008][2009] was reported in the intensive care unit neonatal (NICU) of the Vermont Oxford Network (VON) (12).…”

Section: Introductionmentioning

confidence: 99%

“…Newborn necrotizing enterocolitis (NEC) is a term used to describe a common and devastating gastrointestinal neonatal pathology (1)(2)(3). NEC is an inflammatory process, characterized by intestinal necrosis of variable extension, leading to perforation, generalized peritonitis and death (1,4).…”

Section: Introductionmentioning

confidence: 99%

Diagnostic imaging features of necrotizing enterocolitis: a narrative review

Esposito¹,

Mamone²,

Serafino³

et al. 2017

Quant. Imaging Med. Surg.

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Necrotizing enterocolitis (NEC) is an inflammatory process, characterized by intestinal necrosis of variable extension, leading to perforation, generalized peritonitis and death. The classical pathogenetic theory focuses on mucosal damage related to a stress induced intestinal ischemia leading to mucosal injury and bacterial colonization of the wall. A more recent hypothesis emphasizes the role of immaturity of gastrointestinal and immune system, particularly of the premature, responsible of bowel wall vulnerability and suffering. NEC is the most common gastrointestinal emergency in the newborn, with a higher incidence in the preterm; improvement of neonatal resuscitation techniques enables the survival of premature of very low birth weight (VLBW) with prolongation of hospital stay for perinatal and neonatal care and a higher risk of NEC. Clinical presentation of NEC in newborn ranges from mild forms with moderate gastrointestinal tract disorder and that can heal spontaneously, to very serious forms with fulminant course characterized by perforation, peritonitis, sepsis, disseminated intravascular coagulation (DIC) and shock. Imaging modality in the diagnosis of NEC is historically represented by the plain-film abdominal radiographs which can be performed every 6 hours because of the rapid evolution that may occur in the patient's clinical condition.However ultrasound (US), in recent years, is playing an increasingly important role in the evaluation of early stages of the disease as it provides images in real time of the abdominal structures being able to assess the presence and validity of peristalsis of the bowel loops, detect the thickness of the intestinal wall and the presence of minimal amounts of fluid in the peritoneal cavity. In this paper we review the pathogenesis, clinical presentation and imaging of NEC with a particular attention to the emergent role of US in the diagnosis of the disease.

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Necrotizing Enterocolitis

Cited by 73 publications

References 82 publications

Endothelial TLR4 activation impairs intestinal microcirculatory perfusion in necrotizing enterocolitis via eNOS–NO–nitrite signaling

Endothelial TLR4 activation impairs intestinal microcirculatory perfusion in necrotizing enterocolitis via eNOS–NO–nitrite signaling

Octreotide in a Critically Ill Extremely Preterm Infant With Perforated Necrotizing Enterocolitis

Diagnostic imaging features of necrotizing enterocolitis: a narrative review

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