BACKGROUND-High-dose erythropoietin has been shown to have a neuroprotective effect in preclinical models of neonatal brain injury, and phase 2 trials have suggested possible efficacy; however, the benefits and safety of this therapy in extremely preterm infants have not been established. METHODS-In this multicenter, randomized, double-blind trial of high-dose erythropoietin, we assigned 941 infants who were born at 24 weeks 0 days to 27 weeks 6 days of gestation to receive erythropoietin or placebo within 24 hours after birth.

Late-onset neonatal sepsis is a significant cause of morbidity and mortality, and early detection could prove beneficial. Previously, we found that abnormal heart rate characteristics (HRC) of reduced variability and transient decelerations occurred early in the course of neonatal sepsis and sepsis-like illness in infants in a single neonatal intensive care unit (NICU). We hypothesized that this finding can be generalized to other NICUs. We prospectively collected clinical data and continuously measured RR intervals in all infants in two NICUs who stayed for Ͼ7 d. We defined episodes of sepsis and sepsis-like illness as acute clinical deteriorations that prompted physicians to obtain blood cultures and start antibiotics. A predictive statistical model yielding an HRC index was developed on a derivation cohort of 316 neonates in the University of Virginia NICU and then applied to the validation cohort of 317 neonates in the Wake Forest University NICU. In the derivation cohort, there were 155 episodes of sepsis and sepsis-like illness in 101 infants, and in the validation cohort, there were 118 episodes in 93 infants. In the validation cohort, the HRC index 1) showed highly significant association with impending sepsis and sepsis-like illness (receiver operator characteristic area 0.75, p Ͻ 0.001) and 2) added significantly to the demographic information of birth weight, gestational age, and days of postnatal age in predicting sepsis and sepsis-like illness Abbreviations BW, birth weight GA, gestational age HRC, heart rate characteristics HRV, heart rate variability NICU, neonatal intensive care unit ROC, receiver operating characteristic SampEn, sample entropy UVA, University of Virginia WFU, Wake Forest University Late-onset nosocomial neonatal sepsis occurs after 3 days of life and is a major health problem in high-risk newborn infants in the neonatal intensive care unit (NICU). It occurs in 25% of very low birth weight (Ͻ1500 g) infants and leads to a more than doubling of mortality and a 50% increase in hospital stay (1). Early detection is very difficult using clinical signs and currently available laboratory tests (2, 3). Clinicians have found neither to be reliable (4, 5), and the diagnostic challenge is manifest in the Centers for Disease Control and Prevention's definition that allows diagnosis of neonatal "clinical sepsis" with either a negative blood culture or no blood culture at all (6). These high-stakes uncertainties lead to two shortcomings of the current practice. First, infants with sepsis are often detected only when seriously ill, increasing morbidity and mortality and lowering the chance for prompt, complete recovery with antibiotic therapy. Second, physicians have a very low threshold for suspecting sepsis, and as many as 10 -20 infants are treated unnecessarily for every infant who truly is septic (3-5). The National Institute of Child Health and Human 0031-3998/03/5306-0920 PEDIATRIC RESEARCH Vol. 53, No. 6, 2003 Copyright © 2003 Printed in U.S.A. ABSTRACT920

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Higher PPCV is associated with worse developmental outcome in premature infants at 1-year adjusted age. Maternal anxiety at neonatal discharge predicts later high PPCV. Interventions to prevent or decrease PPCV in premature infants should be targeted at parents who are more anxious at hospital discharge.

Objectives To identify variables associated with successful elective extubation, and to determine neonatal morbidities associated with extubation failure in extremely preterm neonates. Study design This study was a secondary analysis of the National Institute of Child Health and Human Development Neonatal Research Network’s Surfactant, Positive Pressure, and Oxygenation Randomized Trial that included extremely preterm infants born at 240/7 to 276/7 weeks’ gestation. Patients were randomized either to a permissive ventilatory strategy (continuous positive airway pressure group) or intubation followed by early surfactant (surfactant group). There were prespecified intubation and extubation criteria. Extubation failure was defined as reintubation within 5 days of extubation. Results Of 1316 infants in the trial, 1071 were eligible; 926 infants had data available on extubation status; 538 were successful and 388 failed extubation. The rate of successful extubation was 50% (188/374) in the continuous positive airway pressure group and 63% (350/552) in the surfactant group. Successful extubation was associated with higher 5-minute Apgar score, and pH prior to extubation, lower peak fraction of inspired oxygen within the first 24 hours of age and prior to extubation, lower partial pressure of carbon dioxide prior to extubation, and non-small for gestational age status after adjustment for the randomization group assignment. Infants who failed extubation had higher adjusted rates of mortality (OR 2.89), bronchopulmonary dysplasia (OR 3.06), and death/bronchopulmonary dysplasia (OR 3.27). Conclusions Higher 5-minute Apgar score, and pH prior to extubation, lower peak fraction of inspired oxygen within first 24 hours of age, lower partial pressure of carbon dioxide and fraction of inspired oxygen prior to extubation, and nonsmall for gestational age status were associated with successful extubation. Failed extubation was associated with significantly higher likelihood of mortality and morbidities. Trial registration ClinicalTrials.gov: NCT00233324.