; for the the Swiss EPO Neuroprotection Trial Group IMPORTANCE Very preterm infants are at risk of developing encephalopathy of prematurity and long-term neurodevelopmental delay. Erythropoietin treatment is neuroprotective in animal experimental and human clinical studies. OBJECTIVE To determine whether prophylactic early high-dose recombinant human erythropoietin (rhEPO) in preterm infants improves neurodevelopmental outcome at 2 years' corrected age. DESIGN, SETTING, AND PARTICIPANTS Preterm infants born between 26 weeks 0 days' and 31 weeks 6 days' gestation were enrolled in a randomized, double-blind, placebo-controlled, multicenter trial in Switzerland between 2005 and 2012. Neurodevelopmental assessments at age 2 years were completed in 2014. INTERVENTIONS Participants were randomly assigned to receive either rhEPO (3000 IU/kg) or placebo (isotonic saline, 0.9%) intravenously within 3 hours, at 12 to 18 hours, and at 36 to 42 hours after birth. MAIN OUTCOMES AND MEASURES Primary outcome was cognitive development assessed with the Mental Development Index (MDI; norm, 100 [SD, 15]; higher values indicate better function) of the Bayley Scales of Infant Development, second edition (BSID-II) at 2 years corrected age. The minimal clinically important difference between groups was 5 points (0.3 SD). Secondary outcomes were motor development (assessed with the Psychomotor Development Index), cerebral palsy, hearing or visual impairment, and anthropometric growth parameters. RESULTS Among 448 preterm infants randomized (mean gestational age, 29.0 [range, 26.0-30.9] weeks; 264 [59%] female; mean birth weight, 1210 [range, 490-2290] g), 228 were randomized to rhEPO and 220 to placebo. Neurodevelopmental outcome data were available for 365 (81%) at a mean age of 23.6 months. In an intention-to-treat analysis, mean MDI was not statistically significantly different between the rhEPO group (93.5 [SD, 16.0] [95% CI, 91.2 to 95.8]) and the placebo group (94.5 [SD, 17.8] [95% CI, 90.8 to 98.5]) (difference, −1.0 [95% CI, −4.5 to 2.5]; P = .56). No differences were found between groups in the secondary outcomes. CONCLUSIONS AND RELEVANCE Among very preterm infants who received prophylactic early high-dose rhEPO for neuroprotection, compared with infants who received placebo, there were no statistically significant differences in neurodevelopmental outcomes at 2 years. Follow-up for cognitive and physical problems that may not become evident until later in life is required.

BackgroundOver the last two decades, improvements in medical care have been associated with a significant increase and better outcome of very preterm (VP, < 32 completed gestational weeks) and very low birth weight (VLBW, < 1500 g) infants. Only a few publications analyse changes of their short-term outcome in a geographically defined area over more than 10 years. We therefore aimed to investigate the net change of VP- and VLBW infants leaving the hospital without major complications.MethodsOur population-based observational cohort study used the Minimal Neonatal Data Set, a database maintained by the Swiss Society of Neonatology including information of all VP- and VLBW infants. Perinatal characteristics, mortality and morbidity rates and the survival free of major complications were analysed and their temporal trends evaluated.ResultsIn 1996, 2000, 2004, and 2008, a total number of 3090 infants were enrolled in the Network Database. At the same time the rate of VP- and VLBW neonates increased significantly from 0.87% in 1996 to 1.10% in 2008 (p < 0.001). The overall mortality remained stable by 13%, but the survival free of major complications increased from 66.9% to 71.7% (p < 0.01). The percentage of infants getting a full course of antenatal corticosteroids increased from 67.7% in 1996 to 91.4% in 2008 (p < 0.001). Surfactant was given more frequently (24.8% in 1996 compared to 40.1% in 2008, p < 0.001) and the frequency of mechanical ventilation remained stable by about 43%. However, the use of CPAP therapy increased considerably from 43% to 73.2% (p < 0.001). Some of the typical neonatal pathologies like bronchopulmonary dysplasia, necrotising enterocolitis and intraventricular haemorrhage decreased significantly (p ≤ 0.02) whereas others like patent ductus arteriosus and respiratory distress syndrome increased (p < 0.001).ConclusionsOver the 12-year observation period, the number of VP- and VLBW infants increased significantly. An unchanged overall mortality rate and an increase of survivors free of major complication resulted in a considerable net gain in infants with potentially good outcome.

No abstract