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.

Objectives To assess whether late surfactant treatment of extremely low gestational age newborn (ELGAN) infants requiring ventilation at 7–14 days, who often have surfactant deficiency and dysfunction, safely improves survival without bronchopulmonary dysplasia (BPD). Study design ELGAN infants (≤ 28 0/7 weeks) who required mechanical ventilation at 7–14 days were enrolled in a randomized, masked controlled trial at 25 US centers. All infants received inhaled nitric oxide (INO) and either surfactant (calfactant/Infasurf®) or sham instillation every 1–3 days to a maximum of 5 doses while intubated. The primary outcome was survival at 36 weeks postmenstrual age (PMA) without BPD, evaluated by physiologic oxygen/flow reduction. Results Between January 2010 and September 2013, 511 infants were enrolled. There were no differences between treatment groups in mean birth weight (701±164 g), gestational age (25.2±1.2 weeks), percentage <26 weeks (70.6%), race, sex, severity of lung disease at enrollment, or co-morbidities of prematurity. Survival without BPD was not different between treated vs. controls at 36 weeks PMA (31.3% vs. 31.7%; relative benefit 0.98 (95% CI: 0.75, 1.28 p=0.89) or 40 weeks (58.7% vs. 54.1%; relative benefit 1.08:0.92, 1.27 p=0.33). There were no differences between groups in serious adverse events, co-morbidities of prematurity, nor in the severity of lung disease to 36 weeks. Conclusions Late treatment with up to 5 doses of surfactant in ventilated premature infants receiving iNO was well tolerated but did not improve survival without BPD at 36 or 40 weeks. Pulmonary and neurodevelopmental assessments are ongoing.

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Objective To determine the effects of late surfactant on respiratory outcomes determined at one-year corrected age In the Trial of Late Surfactant (TOLSURF), which randomized extremely low gestational age newborns (ELGAN, ≤28 weeks’ gestational age) ventilated at 7–14 days to late surfactant and inhaled nitric oxide versus inhaled nitric oxide-alone (control). Study design Caregivers were surveyed in a double-blinded manner at 3, 6, 9 and 12 months corrected age to collect information on respiratory resource utilization (infant medication use, home support and hospitalization). Infants were classified for composite outcomes of Pulmonary Morbidity (No PM, determined in infants with no reported respiratory resource utilization) and Persistent PM (determined in infants with any resource utilization in ≥3 surveys). Results Infants (n=450, late surfactant n=217, control n=233) were 25.3±1.2 weeks’ gestation and 713±164g at birth. In the late surfactant group, fewer infants received home respiratory support than in the control group [35.8% versus 52.9%, Relative Benefit (RB) 1.28 (1.07, 1.55)]. There was no benefit of late surfactant for No PM versus PM (RB 1.27; 95% CI 0.89, 1.81) or No Persistent PM versus Persistent PM (RB 1.01; 95% CI 0.87, 1.17). After adjustment for imbalances in baseline characteristics, relative benefit of late surfactant treatment increased: RB 1.40 (95% CI 0.89, 1.80) for No PM and RB 1.24 (95% CI 1.08, 1.42) for No Persistent PM. Conclusion Treatment of ELGAN with late surfactant in combination with inhaled nitric oxide decreased use of home respiratory support and may decrease persistent pulmonary morbidity. Trial registration ClinicalTrials.gov: NCT01022580

IMPORTANCE It remains poorly understood how parents decide whether to enroll a child in a neonatal clinical trial. This is particularly true for parents from racial or ethnic minority populations.Understanding factors associated with enrollment decisions may improve recruitment processes for families, increase enrollment rates, and decrease disparities in research participation. OBJECTIVE To assess differences in parental factors between parents who enrolled their infant and those who declined enrollment for a neonatal randomized clinical trial. DESIGN, SETTING, AND PARTICIPANTSThis survey study conducted from July 2017 to October 2019 in 12 US level 3 and 4 neonatal intensive care units included parents of infants who enrolled in the High-dose Erythropoietin for Asphyxia and Encephalopathy (HEAL) trial or who were eligible but declined enrollment. Data were analyzed October 2019 through July 2020. EXPOSURE Parental choice of enrollment in neonatal clinical trial. MAIN OUTCOMES AND MEASURES Percentages and odds ratios (ORs) of parent participation as categorized by demographic characteristics, self-assessment of child's medical condition, study comprehension, and trust in medical researchers. Survey questions were based on the hypothesis that parents who enrolled their infant in HEAL differ from those who declined enrollment across 4 categories: (1) infant characteristics and parental demographic characteristics, (2) perception of infant's illness, (3) study comprehension, and (4) trust in clinicians and researchers. RESULTSOf a total 387 eligible parents, 269 (69.5%) completed the survey and were included in analysis. This included 183 of 242 (75.6%) of HEAL-enrolled and 86 of 145 (59.3%) of HEAL-declined parents. Parents who enrolled their infant had lower rates of Medicaid participation (74 [41.1%] vs 47 [55.3%]; P = .04) and higher rates of annual income greater than $55 000 (94 [52.8%] vs 30 [37.5%]; P = .03) compared with those who declined. Black parents had lower enrollment rates compared with White parents (OR, 0.35; 95% CI, 0.17-0.73). Parents who reported their infant's medical condition as more serious had higher enrollment rates (OR, 5.7; 95% CI, 2.0-16.3). Parents who enrolled their infant reported higher trust in medical researchers compared with parents who declined (mean [SD] difference, 5.3 [0.3-10.3]). There was no association between study comprehension and enrollment. CONCLUSIONS AND RELEVANCEIn this study, the following factors were associated with neonatal clinical trial enrollment: demographic characteristics (ie, race/ethnicity, Medicaid status, and (continued) Key Points Question How do parents with infants enrolled in a neonatal clinical trial differ from those who decline participation? Findings In this survey study including 269 parent responses, participants who enrolled their infant had different demographic characteristics (lower rate of Medicaid participation, higher income, less likely to identify as Black), reported their infant's medical condition as more serious, and reported ...

Background Bloodstream infections (BSIs) cause significant morbidity and mortality in children. Recent pediatric epidemiological data may inform prevention strategies and empiric antimicrobial therapy selection. Methods We conducted a retrospective cohort study from 2009 through 2016 utilizing demographic and microbiologic data on inpatients aged <19 years using the Premier Healthcare Database. BSIs were positive blood cultures without known contaminants. Hospitalization rate was the number of BSI-positive encounters per 1000 admissions. Community-acquired infections (CAIs) were cultures positive ≤2 days of admission among nonneonates. BSI patients were compared to documented positive BSI patients (non-BSI); differences were analyzed using χ2 test, t test, and Cochran-Armitage test for time trends. Results Among 1 809 751 encounters from 162 US hospitals, 5340 (0.30%) were BSI positive; CAIs were most common (50%). BSI patients were more often aged 1–5 years and had complex chronic conditions or central lines compared to non-BSI patients. The BSI hospitalization rate declined nonsignificantly over time (3.13 in 2009 to 2.98 in 2016, P = .08). Among pathogens, Escherichia coli (0.80 to 1.26), methicillin-sensitive Staphylococcus aureus (0.83 to 1.98), and group A Streptococcus (0.16 to 0.37) significantly increased for nonneonates, while Streptococcus pneumoniae (1.07 to 0.26) and Enterococcus spp. (0.60 to 0.17) declined. Regional differences were greatest for E. coli and highest in the New England and South Atlantic regions. Conclusions Trends in pediatric BSI hospitalization rates varied by pathogen and regionally. Overall the BSI hospitalization rate did not significantly decline, indicating a continued need to improve pediatric BSI assessment and prevention.

IMPORTANCE Extremely preterm (EP) infants frequently receive opioids and/or benzodiazepines, but these drugs' association with neurodevelopmental outcomes is poorly understood.OBJECTIVES To describe the use of opioids and benzodiazepines in EP infants during neonatal intensive care unit (NICU) hospitalization and to explore these drugs' association with neurodevelopmental outcomes at 2 years' corrected age. DESIGN, SETTING, AND PARTICIPANTSThis cohort study was a secondary analysis of data from the Preterm Erythropoietin Neuroprotection (PENUT) Trial, which was conducted among infants born between gestational ages of 24 weeks, 0 days, and 27 weeks, 6 days. Infants received care at 19 sites in the United States, and data were collected from December 2013 to September 2016. Data analysis for this study was conducted from March to December 2020. EXPOSURES Short (ie, Յ7 days) and prolonged (ie, >7 days) exposure to opioids and/or benzodiazepines during NICU stay. MAIN OUTCOMES AND MEASURESCognitive, language, and motor development scores were assessed using the Bayley Scales of Infant Development-Third Edition (BSID-III). RESULTS There were 936 EP infants (448 [48%] female infants; 611 [65%] White infants; mean [SD]gestational age, 181 [8] days) included in the study, and 692 (74%) had neurodevelopmental outcome data available. Overall, 158 infants (17%) were not exposed to any drugs of interest, 297 (32%) received either opioids or benzodiazepines, and 481 (51%) received both. Infants exposed to both had adjusted odds ratios of 9.7 (95% CI, 2.9 to 32.2) for necrotizing enterocolitis and 1.7 (95% CI, 1.1 to 2.7) for severe bronchopulmonary dysplasia; they also had a longer estimated adjusted mean difference in length of stay of 34.2 (95% CI, 26.2 to 42.2) days compared with those who received neither drug. After adjusting for site and propensity scores derived for each exposure category, infants exposed to opioids and benzodiazepines had lower BSID-III cognitive, motor, and language scores compared with infants with no exposure (eg, estimated difference in mean scores on cognitive scale: −5.72; 95% CI, -8.88 to -2.57). Prolonged exposure to morphine, fentanyl, midazolam, or lorazepam was associated with lower BSID-III scores compared with infants without exposure (median [interquartile range] motor score, 85 [73-97] vs 97 [91-107]). In contrast, BSID-III scores for infants with short exposure to both opioids and benzodiazepines were not different than those of infants without exposure.

for the Preterm Erythropoietin Neuroprotection Trial Consortium IMPORTANCE Extremely preterm infants are among the populations receiving the highest levels of transfusions. Erythropoietin has not been recommended for premature infants because most studies have not demonstrated a decrease in donor exposure.OBJECTIVES To determine whether high-dose erythropoietin given within 24 hours of birth through postmenstrual age of 32 completed weeks will decrease the need for blood transfusions. DESIGN, SETTING, AND PARTICIPANTSThe Preterm Erythropoietin Neuroprotection Trial (PENUT) is a randomized, double-masked clinical trial with participants enrolled at 19 sites consisting of 30 neonatal intensive care units across the United States. Participants were born at a gestational age of 24 weeks (0-6 days) to 27 weeks (6-7 days). Exclusion criteria included conditions known to affect neurodevelopmental outcomes. Of 3266 patients screened, 2325 were excluded, and 941 were enrolled and randomized to erythropoietin (n = 477) or placebo (n = 464).