There is an association between disease location and gestational age at birth in newborns submitted to surgery due to necrotizing enterocolitis

Feldens, Letícia; Souza, João Carlos Ketzer de; Fraga, José Carlos Soares de

doi:10.1016/j.jped.2017.06.010

Cited by 10 publications

(6 citation statements)

References 19 publications

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“…Moreover, although all segments of the intestine can be affected by NEC, the ileum is the most affected segment in large portions of NEC patients. 48 Thus, we asked whether there are segmental differences in necroptosis gene expression along the intestine and whether this differed between neonatal immature intestine and adult mature intestine. As shown in Figure 6F, using enteroids, we determined that Ripk1, Ripk3, and Mlkl all show the highest expression in the juvenile immature ileum when compared with the juvenile duodenum, juvenile jejunum, or adult ileum ( Figure 6F).…”

Section: Necroptosis Genes Are Up-regulated Specifically In the Diffementioning

confidence: 99%

A Novel Role for Necroptosis in the Pathogenesis of Necrotizing Enterocolitis

Werts

Fulton

Ladd

et al. 2020

Cellular and Molecular Gastroenterology and Hepatology

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Necrotizing enterocolitis is a devastating disease of prematurity characterized by gram-negative bacteria colonization and enterocyte death. We identify a role of Toll-like receptor 4-mediated necroptosis of the intestinal epithelium as a precursor to necrotizing enterocolitis development. BACKGROUND & AIMS: Necrotizing enterocolitis (NEC) is a devastating disease of premature infants characterized by Toll-like receptor 4 (TLR4)-dependent intestinal inflammation and enterocyte death. Given that necroptosis is a proinflammatory cell death process that is linked to bacterial signaling, we investigated its potential role in NEC, and the mechanisms involved. METHODS: Human and mouse NEC intestine were analyzed for necroptosis gene expression (ie, RIPK1, RIPK3, and MLKL), and protein activation (phosphorylated RIPK3). To evaluate a potential role for necroptosis in NEC, the effects of genetic (ie, Ripk3 knockout or Mlkl knockout) or pharmacologic (ie, Nec1s) inhibition of intestinal inflammation were assessed in a mouse NEC model, and a possible upstream role of TLR4 was assessed in Tlr4-deficient mice. The NEC-protective effects of human breast milk and its constituent milk oligosaccharides on necroptosis were assessed in a NEC-in-a-dish model, in which mouse intestinal organoids were cultured as either undifferentiated or differentiated epithelium in the presence of NEC bacteria and hypoxia. RESULTS: Necroptosis was activated in the intestines of human and mouse NEC in a TLR4-dependent manner, and was upregulated specifically in differentiated epithelium of the immature ileum. Inhibition of necroptosis genetically and pharmacologically reduced intestinal-epithelial cell death and mucosal inflammation in experimental NEC, and ex vivo in the NEC-in-a-dish system. Strikingly, the addition of human breast milk, or the human milk oligosaccharide 2 fucosyllactose in the ex vivo system, reduced necroptosis and inflammation. CONCLUSIONS: Necroptosis is activated in the intestinal epithelium upon TLR4 signaling and is required for NEC development, and explains in part the protective effects of breast milk.

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Section: Necroptosis Genes Are Up-regulated Specifically In the Diffementioning

confidence: 99%

A Novel Role for Necroptosis in the Pathogenesis of Necrotizing Enterocolitis

Werts

Fulton

Ladd

et al. 2020

Cellular and Molecular Gastroenterology and Hepatology

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“…A imaturidade digestiva é frequente em prematuros devido a múltiplas defi ciências enzimáticas e metabólicas, que prejudicam a função de absorção e digestão, com aumento de bactérias prejudiciais ao intestino, desencadeando um processo infl amatório, que pode inclusive levar a necrose intestinal, denominado enterocolite necrosante neonatal (ECN) 23 . Prematuros são mais susceptíveis a ECN, assim como os bebês com baixo peso, os quais evoluem e podem necessitar de intervenção cirúrgica.…”

Section: Discussionunclassified

“…Prematuros são mais susceptíveis a ECN, assim como os bebês com baixo peso, os quais evoluem e podem necessitar de intervenção cirúrgica. Importante ressaltar que a menor idade gestacional e menor peso pode favorecer o desfecho óbito para bebês acometidos pela ECN 9,23 .…”

Section: Discussionunclassified

Óbitos precoces de recém-nascidos prematuros em município brasileiro de fronteira

Oliveira

Ferreira

Zilly

et al. 2022

SDH

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Introdução: A prematuridade é um problema de saúde pública global, por representar a principal causa de óbito infantis, sobretudo no período neonatal precoce. Objetivo: Analisar a incidência de óbitos de bebês prematuros hospitalizados e identificar fatores relacionados ao óbito precoce em município brasileiro de fronteira.Método: Estudo analítico, transversal, realizado em Foz do Iguaçu-PR, Brasil. Foram analisados 202 prontuários eletrônicos, entre 2013 e 2017, utilizando-se o teste Qui-quadrado e exato de Fisher, com nível de significância (p<0,05).Resultados: O óbito entre bebês prematuros hospitalizados foi considerado alto (21,3%), sobretudo no período neonatal precoce (p<0,001). Parto vaginal, peso ao nascer inferior a 1.000g, prematuridade extrema, escores de Apgar inferior a sete e intervenções invasivas foram fatores relacionados ao óbito neonatal precoce (p<0,001). A maior utilização de antibióticos foi relacionada ao óbito neonatal tardio e infantil (p<0,001).Conclusão: O incremento da assistência pré-natal, da atenção ao parto e da hospitalização de prematuros pode reduzir a mortalidade infantil, em especial em municípios de vulnerabilidade assistencial por pertencerem em região de fronteira.

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“…An additional difference between preterm and term NEC cases includes location of the disease, severity and overall outcome. The small intestine is more commonly affected in preterm infants while the colon is the more frequent location in term infants [8,11,15]. The trend is the greater the gestational age the more distal the site of intestinal involvement [15].…”

Section: Discussion and Literature Reviewmentioning

confidence: 99%

“…The small intestine is more commonly affected in preterm infants while the colon is the more frequent location in term infants [8,11,15]. The trend is the greater the gestational age the more distal the site of intestinal involvement [15]. Broadly, the preterm infants with NEC have more severe disease when compared with term neonates [1].…”

Section: Discussion and Literature Reviewmentioning

confidence: 99%

Case report: necrotizing enterocolitis with a transverse colonic perforation in a 2-day old term neonate and literature review

Hudson

Byrns

Nizalik

et al. 2021

matern health, neonatol and perinatol

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Background Necrotizing enterocolitis (NEC), while classically discussed in preterm and low birth weight neonates, also occurs in the term infant and accounts for 10% of all NEC cases. Despite there being fewer reported cases of NEC in term infants, these presentations demonstrate differences in the onset, severity and risk factors from the classic presentation observed in premature infants. We present a novel case of term NEC that contravenes the reported literature making departures from clinical presentation, risk factors and location of perforation in an otherwise healthy term two-day old infant born after an uncomplicated pregnancy who presented with hematochezia. Case presentation A healthy term baby born after an uneventful pregnancy presented with bloody stool at 2 days of life who was otherwise well. Investigations revealed pneumoperitoneum from a large proximal transverse colonic perforation secondary to NEC. No typical risk factors for NEC were found. Conclusion Given the life-threatening potential of an unrecognized perforation we recommend the inclusion of NEC on the differential for neonatal hematochezia.

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There is an association between disease location and gestational age at birth in newborns submitted to surgery due to necrotizing enterocolitis

Cited by 10 publications

References 19 publications

A Novel Role for Necroptosis in the Pathogenesis of Necrotizing Enterocolitis

A Novel Role for Necroptosis in the Pathogenesis of Necrotizing Enterocolitis

Óbitos precoces de recém-nascidos prematuros em município brasileiro de fronteira

Case report: necrotizing enterocolitis with a transverse colonic perforation in a 2-day old term neonate and literature review

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