Elevated levels of IL-6 and IGFBP-1 predict low serum IGF-1 levels during continuous infusion of rhIGF-1/rhIGFBP-3 in extremely preterm infants

Research output: Contribution to journalArticle


Objective: Steady state insulin-like growth factor-1 (IGF-1) levels vary significantly during continuous intravenous infusion of recombinant human insulin-like growth factor-1/recombinant human insulin-like growth factor binding protein-3 (rhIGF-1/rhIGFBP-3) in the first weeks of life in extremely preterm infants. We evaluated interleukin-6 (IL-6) and insulin-like growth factor binding protein-1 (IGFBP-1) levels as predictors of low IGF-1 levels. Methods: Nineteen extremely preterm infants were enrolled in a trial, 9 received rhIGF-1/rhIGFBP-3 and 10 received standard neonatal care. Blood samples were analyzed daily for IGF-1, IL-6 and IGFBP-1 during intervention with rhIGF-1/rhIGFBP-3. Results: Thirty seven percent of IGF-1 values during active treatment were <20 μg/L. Among treated infants, higher levels of IL-6, one and two days before sampled IGF-1, were associated with IGF-1 < 20 μg/L, gestational age adjusted OR 1.30 (95% CI 1.03–1.63), p = .026, and 1.57 (95% CI 1.26–1.97), p < .001 respectively. Higher levels of IGFBP-1 one day before sampled IGF-1 was also associated with IGF-1 < 20 μg/L, gestational age adjusted OR 1.74 (95% CI 1.19–2.53), p = .004. Conclusion: In preterm infants receiving continuous infusion of rhIGF-1/rhIGFBP-3, higher levels of IL-6 and IGFBP-1 preceded lower levels of circulating IGF-1. These findings demonstrate a need to further evaluate if inflammation and/or infection suppress serum IGF-1 levels. The trial is registered at ClinicalTrials.gov (NCT01096784).


  • Susanna Klevebro
  • Gunnel Hellgren
  • Ingrid Hansen-Pupp
  • Dirk Wackernagel
  • Boubou Hallberg
  • Jan Borg
  • Aldina Pivodic
  • Lois Smith
  • David Ley
  • Ann Hellström
External organisations
  • Karolinska Institutet
  • Boston Children's Hospital
  • University of Gothenburg
  • Premacure AB
  • Statistiska Konsultgruppen
  • Skåne University Hospital
  • Harvard University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Pediatrics


  • IGF-1, IGFBP-1, IL-6, Inflammation, Preterm infants, rhIGF-1/rhIGFBP-3
Original languageEnglish
Pages (from-to)1-8
Number of pages8
JournalGrowth Hormone and IGF Research
Publication statusPublished - 2020
Publication categoryResearch