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Rigshospitalet - en del af Københavns Universitetshospital
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Supplemental Insulin-Like Growth Factor-1 and Necrotizing Enterocolitis in Preterm Pigs

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DOI

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  1. Radiographic Imaging to Evaluate Food Passage Rate in Preterm Piglets as a Model for Preterm Infants

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Gut transit time, using radiological contrast imaging, to predict early signs of necrotizing enterocolitis

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  3. Mildly Pasteurized Whey Protein Promotes Gut Tolerance in Immature Piglets Compared with Extensively Heated Whey Protein

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Beneficial Effect of Mildly Pasteurized Whey Protein on Intestinal Integrity and Innate Defense in Preterm and Near-Term Piglets

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  • Kristine Holgersen
  • Xiaoyan Gao
  • Rangaraj Narayanan
  • Tripti Gaur
  • Galen Carey
  • Norman Barton
  • Xiaoyu Pan
  • Tik Muk
  • Thomas Thymann
  • Per Torp Sangild
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Background: Recombinant human IGF-1/binding protein-3 (rhIGF-1/BP-3) is currently tested as a therapy in preterm infants but possible effects on the gut, including necrotizing enterocolitis (NEC), have not been tested. The aim of this study was to evaluate if rhIGF-1/BP-3 supplementation in the first days after birth negatively affects clinical variables like growth, physical activity, blood chemistry and hematology and gut maturation (e.g., intestinal permeability, morphology, enzyme activities, cytokine levels, enterocyte proliferation, NEC lesions), using NEC-sensitive preterm pigs as a model for preterm infants. Methods: Preterm pigs were given twice daily subcutaneous injections of rhIGF-1/BP-3 or vehicle. Blood was collected for IGF-1 measurements and gut tissue for NEC evaluation and biochemical analyses on day 5. Results: Baseline circulating IGF-1 levels were low in preterm pigs compared with near-term pigs reared by their mother (<20 vs. 70 ng/ml). Injection with rhIGF-1/BP-3 resulted in increased plasma IGF-1 levels for up to 6 h after injection (>40 ng/mL). rhIGF-1/BP-3 treatment reduced the incidence of severe NEC lesions (7/24 vs.16/24, p = 0.01) and overall NEC severity (1.8 ± 0.2 vs. 2.6 ± 0.3, p < 0.05, with most lesions occurring in colon). In the small intestine, villi length (405 ± 25 vs. 345 ± 33 μm) and activities of the brush border peptidases aminopeptidase N and dipeptidylpeptidase IV were increased in rhIGF-1/BP-3 treated pigs, relative to control pigs (+31-44%, both p < 0.05). The treatment had no effects on body weight, blood chemistry or hematology, except for an increase in blood leucocyte and neutrophil counts (p < 0.05, i.e., reduced neonatal neutropenia). Likewise, rhIGF-1/BP-3 treatment did not affect intestinal tissue cytokine levels (IL-1β, IL-6, IL-8, TNFα,), enterocyte proliferation, goblet cell density, permeability or bacterial translocation to the bone marrow. Conclusion: Supplemental rhIGF-1/BP-3 did not negatively affect any of the measured variables of clinical status or gut maturation in preterm pigs. Longer-term safety and efficacy of exogenous rhIGF-1/BP-3 to support maturation of the gut and other critical organs in preterm newborns remain to be investigated in both pigs and infants.

OriginalsprogEngelsk
Artikelnummer602047
TidsskriftFrontiers in Pediatrics
Vol/bind8
Sider (fra-til)602047
ISSN2296-2360
DOI
StatusUdgivet - 4 feb. 2021

Bibliografisk note

Copyright © 2021 Holgersen, Gao, Narayanan, Gaur, Carey, Barton, Pan, Muk, Thymann and Sangild.

ID: 62427658