Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Supplemental Insulin-Like Growth Factor-1 and Necrotizing Enterocolitis in Preterm Pigs

Research output: Contribution to journalJournal articleResearchpeer-review

DOI

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

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Importance of Comprehensive Molecular Profiling for Clinical Outcome in Children With Recurrent Cancer

    Research output: Contribution to journalJournal articleResearchpeer-review

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

    Research output: Contribution to journalJournal articleResearchpeer-review

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

    Research output: Contribution to journalJournal articleResearchpeer-review

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

    Research output: Contribution to journalJournal articleResearchpeer-review

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

    Research output: Contribution to journalJournal articleResearchpeer-review

  • Kristine Holgersen
  • Xiaoyan Gao
  • Rangaraj Narayanan
  • Tripti Gaur
  • Galen Carey
  • Norman Barton
  • Xiaoyu Pan
  • Tik Muk
  • Thomas Thymann
  • Per Torp Sangild
View graph of relations

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.

Original languageEnglish
JournalFrontiers in Pediatrics
Volume8
Pages (from-to)602047
ISSN2296-2360
DOIs
Publication statusPublished - 2021

ID: 62427658