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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.

Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden. Electronic address: susanna.klevebro@ki.se. Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden; Institute of Bioscience, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden. Lund University, Skåne University Hospital, Department of Clinical Sciences Lund, Pediatrics, Lund, Sweden. Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden. Former Premacure AB, Uppsala, Sweden. Statistiska konsultgruppen, Gothenburg, Sweden. Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA, United States of America. Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.

Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society. 2020;:1-8
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Abstract

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).