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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

Journal article
Authors S. Klevebro
Gunnel Hellgren
I. Hansen-Pupp
D. Wackernagel
B. Hallberg
J. Borg
A. Pivodic
L. Smith
D. Ley
Ann Hellström
Published in Growth Hormone and IGF Research
Volume 50
Pages 1-8
ISSN 1096-6374
Publication year 2020
Published at Institute of Neuroscience and Physiology
Institute of Biomedicine
Pages 1-8
Language en
Keywords IGF-1, IGFBP-1, IL-6, Inflammation, Preterm infants, rhIGF-1/rhIGFBP-3, interleukin 6, mecasermin rinfabate, somatomedin binding protein 1, somatomedin C, Article, blood analysis, clinical article, continuous infusion, controlled study, disease association, female, gestational age, human, infection, male, newborn, newborn care, prediction, prematurity, priority journal, protein blood level, randomized controlled trial
Subject categories Pediatrics


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 (NCT01096784). © 2019

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