ABSTRACT
OBJECTIVE: To investigate recombinant human insulin-like growth factor 1 complexed with its binding protein (rhIGF-1/rhIGFBP-3) for the prevention of retinopathy of prematurity (ROP) and other complications of prematurity among extremely preterm infants. STUDY DESIGN: This phase 2 trial was conducted from September 2014 to March 2016. Infants born at a gestational age of 230/7 weeks to 276/7 weeks were randomly allocated to rhIGF-1/rhIGFBP-3 (250 µg/kg/ 24 hours, continuous intravenous infusion from <24 hours of birth to postmenstrual age 296/7 weeks) or standard neonatal care, with follow-up to a postmenstrual age of 404/7 weeks. Target exposure was ≥70% IGF-1 measurements within 28-109 µg/L and ≥70% intended therapy duration. The primary endpoint was maximum severity of ROP. Secondary endpoints included time to discharge from neonatal care, bronchopulmonary dysplasia, intraventricular hemorrhage, and growth measures. RESULTS: Overall, 61 infants were allocated to rhIGF-1/rhIGFBP-3, 60 to standard care (full analysis set); 24 of 61 treated infants achieved target exposure (evaluable set). rhIGF-1/rhIGFBP-3 did not decrease ROP severity or ROP occurrence. There was, however, a 53% decrease in severe bronchopulmonary dysplasia in the full analysis set (21.3% treated vs 44.9% standard care), and an 89% decrease in the evaluable set (4.8% vs 44.9%; P = .04 and P = .02, respectively) for severity distribution between groups. There was also a nonsignificant trend toward decrease in grades 3-4 intraventricular hemorrhage in the full analysis set (13.1% vs 23.3%) and in the evaluable set (8.3% vs 23.3%). Fatal serious adverse events were reported in 19.7% of treated infants (12/61) and 11.7% of control infants (7/60). No effect was observed on time to discharge from neonatal care/growth measures. CONCLUSIONS: rhIGF-1/rhIGFBP-3 did not affect development of ROP, but decreased the occurrence of severe bronchopulmonary dysplasia, with a nonsignificant decrease in grades 3-4 intraventricular hemorrhage. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01096784.
Subject(s)
Cerebral Hemorrhage/prevention & control , Insulin-Like Growth Factor I/therapeutic use , Recombinant Proteins/therapeutic use , Retinopathy of Prematurity/prevention & control , Bronchopulmonary Dysplasia/prevention & control , Cerebral Hemorrhage/therapy , Female , Gestational Age , Humans , Infant, Extremely Premature , Infant, Newborn , Infant, Premature , Infusions, Intravenous , Insulin-Like Growth Factor Binding Protein 3/therapeutic use , Male , Retinopathy of Prematurity/mortality , Retinopathy of Prematurity/therapy , Severity of Illness Index , Treatment OutcomeABSTRACT
OBJECTIVE: To assess visual function in low-risk preterm infants at 3, 5, and 12 months corrected age to determine whether the maturation of visual function in the first year is similar to that reported in term-born infants. STUDY DESIGN: Seventy-five low-risk infants (25.0-30.9 weeks gestation) underwent ophthalmological examinations and a battery of tests (fix and follow, visual fields, acuity, attention at distance, and fixation shift) designed to assess various aspects of visual function at 3, 5, and 12 months corrected age. RESULTS: The results were comparable with normative data from term-born infants in all tests but fixation shift, suggesting that maturation of most aspects of visual function is not significantly affected by preterm birth. In contrast, >25% of preterm infants failed the fixation shift test at 3 months, with a higher percentage of failing at 5 and 12 months. CONCLUSIONS: There is a specific profile of early visual behavior in low-risk preterm infants, with a high percentage of infants failing a test that specifically assesses visual attention and provides a measure of cortical processing.