AUTHOR=Horsch Sandra , Parodi Alessandro , Hallberg Boubou , Malova Mariya , Björkman-Burtscher Isabella M. , Hansen-Pupp Ingrid , Marlow Neil , Beardsall Kathryn , Dunger David , van Weissenbruch Mirjam , Smith Lois E. H. , Hamdani Mohamed , Mangili Alexandra , Barton Norman , Ramenghi Luca A. , Hellström Ann , Ley David ,  ROPP-2008-01 Study Team 

TITLE=Randomized Control Trial of Postnatal rhIGF-1/rhIGFBP-3 Replacement in Preterm Infants: Post-hoc Analysis of Its Effect on Brain Injury

JOURNAL=Frontiers in Pediatrics

VOLUME=8

YEAR=2020

URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2020.517207

DOI=10.3389/fped.2020.517207

ISSN=2296-2360

ABSTRACT=<p><bold>Background:</bold> Postnatal insulin-like growth factor-1 (IGF-1) replacement with recombinant human (rh)IGF-1 and IGF binding protein-3 (rhIGF-1/rhIGFBP-3) is being studied as a potential treatment to reduce comorbidities of prematurity. We have recently reported on a phase II, multicenter, randomized, controlled trial comparing postnatal rhIGF-1/rhIGFBP-3 replacement with standard of care (SOC) in extremely preterm infants (NCT01096784). Maximum severity of retinopathy of prematurity was the primary endpoint of the trial and presence of GMH-IVH/PHI one of the pre-specified secondary endpoints. Infants therefore received serial cranial ultrasound scans (CUS) between birth and term age. In this <italic>post-hoc</italic> analysis we present a detailed analysis of the CUS data of this trial and evaluate the effect of postnatal rhIGF-1/rhIGFBP-3 replacement on the incidence of different kinds of brain injury in extremely preterm infants.</p><p><bold>Methods:</bold> This report is an exploratory <italic>post-hoc</italic> analysis of a phase II trial in which infants &lt;28 weeks gestational age were randomly allocated to rhIGF-1/rhIGFBP-3 or SOC. Serial cranial ultrasounds were performed between birth and term-equivalent age. Presence of germinal matrix hemorrhage and intraventricular hemorrhage (GMH-IVH), periventricular hemorrhagic infarction (PHI), post-hemorrhagic ventricular dilatation, and white matter injury (WMI) were scored by two independent masked readers.</p><p><bold>Results:</bold> The analysis included 117 infants; 58 received rhIGF-1/rhIGFBP-3 and 59 received SOC. A trend toward less grade II–III GMH-IVH and PHI was observed in treated infants vs. SOC. A subanalysis of infants without evidence of GMH-IVH at study entry (<italic>n</italic> = 104) showed reduced progression to GMH-IVH in treated infants (25.0% [13/52] vs. 40.4% [21/52]; not significant). No effects of rhIGF-1/rhIGFBP-3 on WMI were observed.</p><p><bold>Conclusion:</bold> The potential protective effect of rhIGF-1/rhIGFBP-3 on the occurrence of GMH-IVH/PHI appeared most pronounced in infants with no evidence of GMH-IVH at treatment start.</p>