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

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).

Keywords: IGF-1; IGFBP-1; IL-6; Inflammation; Preterm infants; rhIGF-1/rhIGFBP-3.

Conflict of interest statement

Declaration of Competing Interest IH-P, DL and AH hold stock/stock options in Premalux AB, and have received consulting fees from Shire PLC. BH has received consulting fees from Premacure AB and Shire PLC, and grant/research support from Baxter. JB holds stock in Premalux AB.

Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.

Figures

Fig. 1.

Biomarkers over time for treated infants during active and non-active treatment periods and controls. Individual values, estimated mean and 95% CI for active intervention (blue unfilled circles, solid line), non-active intervention (red filled circles, short dash line) and controls (green triangles, long dash line) are demonstrated. a: Insulin-like growth factor-1 (IGF-1, μg/L) b: Interleukin-6 (IL-6, pg/mL) c: Insulin-like growth factor binding protein-1 (IGFBP-1, μg/L). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 2.

Estimated probability for IGF1