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Cardiac and Inflammatory Necrotizing Enterocolitis in Newborns Are Not the Same Entity
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 developme...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815686/ https://www.ncbi.nlm.nih.gov/pubmed/33490000 http://dx.doi.org/10.3389/fped.2020.593926 |
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author | Klinke, Michaela Wiskemann, Hanna Bay, Benjamin Schäfer, Hans-Jörg Pagerols Raluy, Laia Reinshagen, Konrad Vincent, Deirdre Boettcher, Michael |
author_facet | Klinke, Michaela Wiskemann, Hanna Bay, Benjamin Schäfer, Hans-Jörg Pagerols Raluy, Laia Reinshagen, Konrad Vincent, Deirdre Boettcher, Michael |
author_sort | Klinke, Michaela |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7815686 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-78156862021-01-21 Cardiac and Inflammatory Necrotizing Enterocolitis in Newborns Are Not the Same Entity Klinke, Michaela Wiskemann, Hanna Bay, Benjamin Schäfer, Hans-Jörg Pagerols Raluy, Laia Reinshagen, Konrad Vincent, Deirdre Boettcher, Michael Front Pediatr Pediatrics 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. Frontiers Media S.A. 2021-01-06 /pmc/articles/PMC7815686/ /pubmed/33490000 http://dx.doi.org/10.3389/fped.2020.593926 Text en Copyright © 2021 Klinke, Wiskemann, Bay, Schäfer, Pagerols Raluy, Reinshagen, Vincent and Boettcher. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pediatrics Klinke, Michaela Wiskemann, Hanna Bay, Benjamin Schäfer, Hans-Jörg Pagerols Raluy, Laia Reinshagen, Konrad Vincent, Deirdre Boettcher, Michael Cardiac and Inflammatory Necrotizing Enterocolitis in Newborns Are Not the Same Entity |
title | Cardiac and Inflammatory Necrotizing Enterocolitis in Newborns Are Not the Same Entity |
title_full | Cardiac and Inflammatory Necrotizing Enterocolitis in Newborns Are Not the Same Entity |
title_fullStr | Cardiac and Inflammatory Necrotizing Enterocolitis in Newborns Are Not the Same Entity |
title_full_unstemmed | Cardiac and Inflammatory Necrotizing Enterocolitis in Newborns Are Not the Same Entity |
title_short | Cardiac and Inflammatory Necrotizing Enterocolitis in Newborns Are Not the Same Entity |
title_sort | cardiac and inflammatory necrotizing enterocolitis in newborns are not the same entity |
topic | Pediatrics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815686/ https://www.ncbi.nlm.nih.gov/pubmed/33490000 http://dx.doi.org/10.3389/fped.2020.593926 |
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