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Intestinal intraluminal glycerol and plasma I-FABP levels in preterm infants with necrotizing enterocolitis
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery. (Barnkirurgi/Christofferson)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery. (Barnkirurgi/Christofferson)
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2016 (English)In: Clinics in Surgery, Vol. 1, no 1085, 1-6 p.Article in journal (Refereed) Published
Abstract [en]

Background/Purpose: Necrotizing enterocolitis (NEC) is highly associated with prematurity and is characterized by bowel necrosis and multi-organ failure. There is a strong need for improved diagnostic methods to reduce the significant morbidity and mortality associated with NEC. The aim of this single centre prospective study was to investigate the possibility to detect early signs of NEC, by using rectal intraluminal microdialysis and plasma intestinal fatty acid binding protein (I-FABP) in preterm infants admitted to a level III neonatal intensive care unit.

Methods: The study was performed on extremely preterm infants with a gestational age of less than 28 weeks. During a 4-week period after birth, rectal intraluminal microdialysate levels of glucose, lactate, pyruvate and glycerol were measured, and plasma was collected for I-FABP analysis. Infants not developing NEC served as controls.

 Results: Microdialysis revealed signs of intestinal hypoxic or ischemic damage and cell membrane degradation, with a marked increase of both intraluminal glycerol and plasma I-FABP in infants developing NEC, as well as in infants suffering from other complications. The microdialysate levels of glucose, lactate and pyruvate were too low to be evaluated in this setting. All infants tolerated the microdialysis well without any complications.

Conclusion: Elevated levels of intraluminal glycerol and plasma I-FABP suggests mucosal cell membrane degradation and hypoxic or ischemic damage in preterm infants developing NEC, as well as in preterm infants suffering from other complications such as volvulus, sepsis or respiratory distress. However, it was not possible to predict development of NEC before clinical diagnosis using these markers. 

Place, publisher, year, edition, pages
2016. Vol. 1, no 1085, 1-6 p.
National Category
Surgery
Research subject
Pediatric Surgery
Identifiers
URN: urn:nbn:se:uu:diva-197752OAI: oai:DiVA.org:uu-197752DiVA: diva2:614033
Available from: 2013-04-03 Created: 2013-04-03 Last updated: 2017-01-04
In thesis
1. Experimental and Clinical Necrotizing Enterocolitis
Open this publication in new window or tab >>Experimental and Clinical Necrotizing Enterocolitis
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Necrotizing enterocolitis (NEC), a severe inflammatory disorder of the gastrointestinal tract with high morbidity and mortality, affects primarily preterm infants. The diagnosis represents a challenging task, and no biomarker has been found to aid early diagnosis with high accuracy. Microdialysis has been widely used to detect metabolites of anaerobic metabolism, enabling a local and early detection of ischemia. This thesis aims to evaluate the possibility of detecting intestinal ischemic stress in experimental and clinical  NEC, by use of rectal intraluminal microdialysis.

Intraluminal rectal microdialysis was performed on rats subjected to total intestinal ischemia. Metabolites of ischemia were detectable in both ileum and rectum, with raised glycerol concentrations and lactate/pyruvate ratios. Elevated concentrations of glycerol correlated to increasing intestinal histopathological injury.

Experimental early NEC was induced in newborn rat pups, by hypoxia/re-oxygenation treatment. Development of NEC was confirmed by histopathology. Elevated glycerol concentrations were detected by rectal microdialysis.

The genetic alterations following experimental NEC in rat pups were studied with microarray. Immunohistochemistry staining was performed for tight junction proteins claudin-1 and claudin-8. Several genes were altered in experimental NEC, mainly genes regulating tight junctions and cell adhesion. Immunohistochemistry revealed reduced expression of claudin-1.

A prospective study was conducted on preterm infants with a gestational age of less than 28 weeks. The infants were admitted to a neonatal intensive care unit, and observed during a 4-week period. Rectal microdialysis was performed twice a week, and blood was drawn for analysis of I-FABP. A total of 15 infants were included in the study, whereof four infants developed NEC, and 11 served as controls. Rectal glycerol and I-FABP displayed high concentrations, which varied considerably during the observation periods, both in NEC and controls. No differences in either glycerol or I-FABP concentrations were seen in the NEC-group vs. the controls.

In conclusion, rectal microdialysis can detect metabolites of intestinal ischemia, both in experimental and clinical NEC. Rectal microdialysis is safe and could provide a valuable non-invasive aid to detect hypoxia-induced intestinal damage or ischemic stress in extremely preterm infants. In this study however, it was not possible to predict the development of clinical NEC using microdialysis or I-FABP.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2013. 47 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 898
Keyword
Necrotizing, Enterocolitis, Ischemia, Microdialysis, Intraluminal, I-FABP
National Category
Surgery
Research subject
Pediatric Surgery
Identifiers
urn:nbn:se:uu:diva-197754 (URN)978-91-554-8655-6 (ISBN)
Public defence
2013-05-30, Rosénsalen, Ing 95/96, NB, Akademiska Barnsjukhuset, Uppsala, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2013-05-06 Created: 2013-04-03 Last updated: 2013-08-30Bibliographically approved

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