Safety aspects of longitudinal administration of IGF-I/IGFBP-3 complex in neonatal mice (original) (raw)
Related papers
Postnatal serum insulin-like growth factor i and retinopathy of prematurity
Journal of American Association for Pediatric Ophthalmology and Strabismus, 2015
INTRODUCTION-Low serum insulin-like growth factor 1 (IGF-1) has been associated with development of severe retinopathy of prematurity (ROP), but no U.S. studies have been reported. We sought to determine the relationship between postnatal serum IGF-1 levels and severe ROP in a racially diverse U.S. cohort. METHODS-Prospective cohort study of 74 infants with birth weight (BW) <1251g and a known ROP outcome at 3 Philadelphia hospitals. Weekly postnatal filter-paper bloodspot IGF-1 assays) were measured through 42 weeks postmenstrual age (PMA). RESULTS-The cohort included 20 Caucasian, 45 black, 2 Asian, and 9 other infants; median gestational age (GA) 27.6 weeks (range 23-33); median BW 975g (range 490-1250). During PMA weeks 28 to 33, mean IGF-1 was 20.0 ng/mL(SE 0.52) for no ROP (n=46), 18.0(0.49) for stage 1 or 2 (n=23), and 17.0(0.70) for stage 3 (n=5, 2 lasered) (p=0.003). Adjustment for BW and GA showed similar results. CONCLUSION-Presence and timing of an association between low postnatal serum IGF and ROP in a racially diverse U.S. sample were found to be consistent with European cohorts. This association provides the pathophysiological basis for growth-based predictive models, which could improve efficiency of ROP screening. Keywords Insulin-like growth factor 1; Prematurity; Retinopathy of prematurity Retinopathy of prematurity (ROP) is a disease of the developing retinal vasculature and is a leading cause of blindness in children worldwide. 1-3 ROP pathogenesis is thought to involve multiple factors, including stage of retinal development and metabolic demand, retinal
Iranian journal of pediatrics, 2013
To evaluate early aggressive vs. conservative nutrition and its effect on Retinopathy of Prematurity (ROP) in <32 weeks of gestation neonates. A prospective, randomized, clinical study was conducted in NICU with a total of 75 preterm infants. In the intervention group, infants received early aggressive nutrition immediately after birth, in the control group infants were started on conventional parenteral nutrition (PN). Blood samples were obtained for Insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP3) levels before commencement of PN on the first postnatal day, and from week 1 to 6 every week. All the infants were examined for ROP. Infants in the early aggressive group had a reduction in the risk of ROP of 5% (2 from 40); the number of infants needed treatment averaged 3.7 (2.7 to 5.2). A total of 11 neonates in the conventional group were detected having ROP (P<0.05). Overall, IGF-I levels were higher in the aggressive PN (APN) vs t...
2012
Objective: Retinopathy of prematurity (ROP) is a blinding disease, initiated by the lack of retinal vascular growth after preterm birth. In Vitro, lack of insulin-like growth factor I (IGF-I) prevents normal retinal vascular growth. The present study was conducted to determine if low serum IGF-I levels in premature infants is associated with a higher incidence of retinopathy and therefore may be used as a prognostic factor for the occurrence of such events. Patients and methods: A prospective study was carried out at the neonatology intensive care unit of Cairo University in the period from June 2007 to June 2009 and included forty infants The inclusion criteria were: gestational age under 32 weeks or weight at birth < 1,500 g. Twenty healthy full term infants selected randomly during the same time period constituted the control group. Results: Of the 40 premature babies recruited, 17 (42.5%) developed some degree of retinopathy during the course of the study, among the 17 cases ...
2012
Abstract: Objective: Retinopathy of prematurity (ROP) is a blinding disease, initiated by the lack of retinal vascular growth after preterm birth. In Vitro, lack of insulin-like growth factor I (IGF-I) prevents normal retinal vascular growth. The present study was conducted to determine if low serum IGF-I levels in premature infants is associated with a higher incidence of retinopathy and therefore may be used as a prognostic factor for the occurrence of such events. Patients and methods: A prospective study was carried out at the neonatology intensive care unit of Cairo University in the period from June 2007 to June 2009 and included forty infants The inclusion criteria were: gestational age under 32 weeks or weight at birth < 1,500 g. Twenty healthy full term infants selected randomly during the same time period constituted the control group. Results: Of the 40 premature babies recruited, 17 (42.5%) developed some degree of retinopathy during the course of the study, among the...
IGF-1 as a drug for preterm infants: a step-wise clinical development
Current pharmaceutical design, 2017
Insulin-like growth factor 1 (IGF-1) is a mitogenic hormone involved in many processes such as growth, metabolism, angiogenesis and differentiation. After very preterm birth, energy demands increase while maternal supplies of nutrients and other factors are lost and the infant may become dependent on parenteral nutrition for weeks. Low postnatal IGF-1 concentrations in preterm infants are associated with poor weight gain, retinopathy of prematurity (ROP) and other morbidities. We will describe the process by which we aim to develop supplementation with recombinant human (rh) IGF-1 and its binding protein rhIGFBP-3 as a possible therapy to promote growth and maturation and reduce morbidities in extremely preterm infants. In order to calculate a dose of IGF-1 tolerated by neonates, a pharmacokinetic study of transfusion with fresh frozen plasma was performed, which provided a relatively low dose of IGF-1, (on average 1.4 μg/kg), that increased serum IGF-1 to levels close to those obse...
Proceedings of the National Academy of Sciences, 2001
Retinopathy of prematurity is a blinding disease, initiated by lack of retinal vascular growth after premature birth. We show that lack of insulin-like growth factor I (IGF-I) in knockout mice prevents normal retinal vascular growth, despite the presence of vascular endothelial growth factor, important to vessel development. In vitro , low levels of IGF-I prevent vascular endothelial growth factor-induced activation of protein kinase B (Akt), a kinase critical for endothelial cell survival. Our results from studies in premature infants suggest that if the IGF-I level is sufficient after birth, normal vessel development occurs and retinopathy of prematurity does not develop. When IGF-I is persistently low, vessels cease to grow, maturing avascular retina becomes hypoxic and vascular endothelial growth factor accumulates in the vitreous. As IGF-I increases to a critical level, retinal neovascularization is triggered. These data indicate that serum IGF-I levels in premature infants can...
Retinopathy of prematurity and serum level of insulin-like growth factor-1
Acta clinica Croatica, 2012
The aim of our study was to measure and compare serum insulin-like growth factor-1 (IGF-1) levels at postmenstrual age of 33 weeks between preterm infants with and without retinopathy of prematurity (ROP). ROP occurs in two phases. Low serum levels of IGF-1 during ROP phase 1 have been found to correlate with the severity of ROP. ROP phase 2 begins around postmenstrual week 33. We conducted a prospective cohort study to measure serum IGF-1 levels in premature infants at postmenstrual age of 33 weeks. The study included all premature infants (N = 74), gestational age < or = 33 weeks, hospitalized at Department of Neonatology, Clinical Center of Montenegro, from April 2008 to July 2009. The incidence of ROP in the study cohort was 50.7%. Infants with ROP had a significantly lower birth weight and significantly shorter gestational age. The mean level of IGF-1 at postmenstrual age of 33 weeks was 23.7 mcg/L. Study results showed that there was no significant difference in serum IGF-1...
Pediatric Research, 2013
Background: In preterm infants, low levels of insulin-like growth factor-I (IGF-I) and IGF binding protein 3 (IGFBP-3) are associated with impaired brain growth and retinopathy of prematurity (ROP). Treatment with IGF-I/IGFBP-3 may be beneficial for brain development and may decrease the prevalence of ROP. Methods: In a phase II pharmacokinetics and safety study, five infants (three girls) with a median (range) gestational age (Ga) of 26 wk + 6 d (26 wk + 0 d to 27 wk + 2 d) and birth weight of 990 (900-1,212) g received continuous intravenous infusion of recombinant human (rh)IGF-I/rhIGFBP-3. Treatment was initiated during the first postnatal day and continued for a median (range) duration of 168 (47-168) h in dosages between 21 and 111 µg/kg/24 h. results: Treatment with rhIGF-I/rhIGFBP-3 was associated with higher serum IGF-I and IGFBP-3 concentrations (P < 0.001) than model-predicted endogenous levels. Of 74 IGF-I samples measured during study drug infusion, 37 (50%) were within the target range, 4 (5%) were above, and 33 (45%) were below. The predicted dose of rhIGF-I/rhIGFBP-3 required to establish circulating levels of IGF-I within the intrauterine range in a 1,000 g infant was 75-100 µg/kg/24 h. No hypoglycemia or other adverse effects were recorded. conclusion: In this study, continuous intravenous infusion of rhIGF-I/rhIGFBP-3 was effective in increasing serum concentrations of IGF-I and IGFBP-3, and was found to be safe.