Necrotizing Enterocolitis: Updates on Morbidity and Mortality Outcomes

Flahive, Colleen; Schlegel, Amy; Mezoff, Ethan A.

doi:10.1016/j.jpeds.2019.12.035

Cited by 23 publications

(19 citation statements)

References 14 publications

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“…NEC is an acute bowel necrosis that mainly affects premature infants, in which the mortality rate is 23.5%. [ 20 ] Survivors may have serious sequelae, ranging from gastrointestinal complications, to severe neurodevelopmental retardation. [ 14 ] Since the initial description of NEC, there has been little change in total mortality and treatment outcomes.…”

Section: Discussionmentioning

confidence: 99%

Lipidomic Profiling of Human Milk Derived Exosomes and Their Emerging Roles in the Prevention of Necrotizing Enterocolitis

Chen

Qian

et al. 2021

Molecular Nutrition Food Res

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Scope: Human milk can prevent the development of necrotizing enterocolitis (NEC). Human milk is rich in cargo-carrying exosomes that participate in intercellular communication. This study investigated the effects of term and preterm human milk-derived exosomes, and elucidated their lipid expression profiles. Methods and Results: Milk from healthy mothers is collected who have delivered full-term or preterm infants, and exosomes are isolated and quantified. Administration of term and preterm milk exosomes significantly enhances epithelial proliferation and migration in vitro, and ameliorates the severity of NEC in vivo. A total of 395 lipids are identified in term and preterm human milk-derived exosomes. Bioinformatics analysis and western blotting reveal that top 50 lipids regulate intestinal epithelial cell function via the Extracellular-Signal-Regulated Kinase/Mitogen Activated Protein Kinase (ERK/MAPK) pathway. Conclusion: This study reveals for the first time the lipidomic complexities in exosomes derived from preterm and term milk. The results provide novel mechanistic insight on how human milk prevents the development of NEC.

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Section: Discussionmentioning

confidence: 99%

Lipidomic Profiling of Human Milk Derived Exosomes and Their Emerging Roles in the Prevention of Necrotizing Enterocolitis

Chen

Qian

et al. 2021

Molecular Nutrition Food Res

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“…ecrotizing enterocolitis (NEC) is an often fatal disease of premature infants that is characterized by the acute onset of inflammation and necrosis of the intestine, leading to overwhelming sepsis and death 1,2 . NEC develops in the setting of premature birth, the administration of formula feeds, and bacterial colonization of the newborn gastrointestinal tract, and caries a 30% mortality rate 3 . In seeking to understand the pathogenesis of NEC, we [4][5][6] and others 7,8 have shown that exaggerated signaling of the receptor for bacterial lipopolysaccharide, namely toll-like receptor 4 (TLR4), on the intestinal epithelium 5 plays a critical role in NEC development.…”

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confidence: 99%

Maternal aryl hydrocarbon receptor activation protects newborns against necrotizing enterocolitis

et al. 2021

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Necrotizing enterocolitis (NEC) is a disease of premature infants characterized by acute intestinal necrosis. Current dogma suggests that NEC develops in response to post-natal dietary and bacterial factors, and so a potential role for in utero factors in NEC remains unexplored. We now show that during pregnancy, administration of a diet rich in the aryl hydrocarbon receptor (AHR) ligand indole-3-carbinole (I3C), or of breast milk, activates AHR and prevents NEC in newborn mice by reducing Toll-like receptor 4 (TLR4) signaling in the newborn gut. Protection from NEC requires activation of AHR in the intestinal epithelium which is reduced in mouse and human NEC, and is independent of leukocyte activation. Finally, we identify an AHR ligand (“A18”) that limits TLR4 signaling in mouse and human intestine, and prevents NEC in mice when administered during pregnancy. In summary, AHR signaling is critical in NEC development, and maternally-delivered, AHR-based therapies may alleviate NEC.

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Section: Introductionmentioning

confidence: 99%

“…Necrotizing enterocolitis (NEC) is one of the most devastating diseases of newborn and preterm infants and has numerous short-and long-term physiological and psychological consequences (1). Despite improvement of neonatal care and the development of novel treatment options, the morbidity and mortality rates of NEC remain high (1). However, due to overall improvements in neonatal care, such as the introduction of donated breast milk, the incidence rate of NEC has been increasing steadily in parallel with rising survival rates of premature infants -the patient population at greatest risk for developing NEC (2)(3)(4).…”

Section: Introductionmentioning

confidence: 99%

Cardiac and Inflammatory Necrotizing Enterocolitis in Newborns Are Not the Same Entity

et al. 2021

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Background: Necrotizing enterocolitis (NEC) is an often-fatal neonatal disease involving intestinal hyperinflammation leading to necrosis. Despite ongoing research, (1) conflicting results and (2) comorbidities of NEC patients make early NEC detection challenging and may complicate therapy development. Most research suggests that NEC pathogenesis is multifactorial, involving a combination of (1) gut prematurity; (2) abnormal bacterial colonization; and (3) ischemia-reperfusion (I/R) injury. As neutrophil extracellular traps (NETs) partially mediate I/R injury and drive inflammation in NEC, we hypothesized that NETs contribute to NEC development; particularly in cardiac patients.Methods: A retrospective analysis of baseline characteristics, clinical signs, laboratory parameters, and imaging was conducted for surgically verified NEC cases over 10 years. Patients were stratified into two groups: (1) prior medically or surgically treated cardiac disease (cardiac NEC) and (2) no cardiac comorbidities (inflammatory NEC). Additionally, histology was reassessed for neutrophil activation and NETs formation.Results: A total of 110 patients (cNEC 43/110 vs. iNEC 67/110) were included in the study, with cNEC neonates being significantly older than iNEC neonates (p = 0.005). While no significant differences were found regarding clinical signs and imaging, laboratory parameters revealed that cNEC patients have significantly increased leucocyte (p = 0.024) and neutrophil (p < 0.001) counts. Both groups also differed in pH value (p = 0.011). Regarding histology: a non-significant increase in staining of myeloperoxidase within the cNEC group could be found in comparison to iNEC samples. Neutrophil elastase (p = 0.012) and citrullinated histone H3 stained (p = 0.041) slides showed a significant markup for neonates diagnosed with cNEC in comparison to neonates with iNEC.Conclusion: The study shows that many standardized methods for diagnosing NEC are rather unspecific. However, differing leucocyte and neutrophil concentrations for iNEC and cNEC may indicate a different pathogenesis and may aid in diagnosis. As we propose that iNEC is grounded rather in sepsis and neutropenia, while cNEC primarily involves I/R injuries, which involves neutrophilia and NETs formation, it is plausible that I/R injury due to interventions for cardiac comorbidities results in pronounced neutrophil activation followed by a hyperinflammation reaction and NEC. However, prospective studies are necessary to validate these findings and to determine the accuracy of the potential diagnostic parameters.

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Necrotizing Enterocolitis: Updates on Morbidity and Mortality Outcomes

Cited by 23 publications

References 14 publications

Lipidomic Profiling of Human Milk Derived Exosomes and Their Emerging Roles in the Prevention of Necrotizing Enterocolitis

Lipidomic Profiling of Human Milk Derived Exosomes and Their Emerging Roles in the Prevention of Necrotizing Enterocolitis

Maternal aryl hydrocarbon receptor activation protects newborns against necrotizing enterocolitis

Cardiac and Inflammatory Necrotizing Enterocolitis in Newborns Are Not the Same Entity

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