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OBJECTIVE: Oxidant injury and lung inflammation in extremely premature infants are associated with the development of bronchopulmonary dysplasia. Surfactant dysfunction resulting from these events may contribute to the pathogenesis of bronchopulmonary dysplasia. Treatment with exogenous surfactant may decrease the incidence or severity of bronchopulmonary dysplasia. We conducted a masked, multicenter, multinational, randomized, controlled, pilot study to estimate the effects of treating infants at high risk for developing bronchopulmonary dysplasia with lucinactant, a synthetic, peptide-containing surfactant, on safety during dosing and the incidence of death or bronchopulmonary dysplasia. METHODS: Preterm infants between 600 and 900 g requiring mechanical ventilation and a fraction of inspired oxygen of > or =0.30 between 3 and 10 days of age were randomly assigned to receive either sham air (placebo) or 1 of 2 doses of lucinactant (90 or 175 mg/kg total phospholipid) every 48 hours to a maximum of 5 doses, if they remained on mechanical ventilation. RESULTS: Of 136 infants enrolled at 34 sites, 44 received placebo, 47 received 90 mg/kg total phospholipid, and 45 received 175 mg/kg total phospholipid. The 90 mg/kg group had a significantly higher percentage of boys (64%) compared with the placebo group (39%); no other significant differences in baseline characteristics among groups were present. Compared with placebo, both the 90 mg/kg and 175 mg/kg groups experienced a significantly higher incidence of desaturation and bradycardia during dosing. Twenty-four hours after dosing, the mean fraction of inspired oxygen was lower in both lucinactant groups (33%) compared with the placebo group (39%). The incidence of mortality or bronchopulmonary dysplasia was 66% in the placebo group, 79% in the 90 mg/kg group, and 58% in the 175 mg/kg group. These differences were not statistically significant. There were no statistical differences among groups for pneumothorax, pulmonary interstitial emphysema, intraventricular hemorrhage, periventricular leukomalacia, retinopathy of prematurity, or mortality. CONCLUSIONS: There were trends toward lower oxygen requirements and toward a lower incidence of mortality or bronchopulmonary dysplasia at 36 weeks' postmenstrual age in infants who received the higher dose of lucinactant, and this warrants further investigation. [ABSTRACT FROM AUTHOR]

Abstract Background To develop an accurate, proxy-reported bedside measurement tool for assessment of the severity of bronchopulmonary dysplasia (also called chronic lung disease) in preterm infants to supplement providers' current biometric measurements of the disease. Methods We adapted Patient-Reported Outcomes Measurement Information System (PROMIS) methodology to develop the Proxy-Reported Pulmonary Outcomes Scale (PRPOS). A multidisciplinary group of registered nurses, nurse practitioners, neonatologists, developmental specialists, and feeding specialists at five academic medical centers participated in the PRPOS development, which included five phases: (1) identification of domains, items, and responses; (2) item classification and selection using a modified Delphi process; (3) focus group exploration of items and response options; (4) cognitive interviews on a preliminary scale; and (5) final revision before field testing. Results Each phase of the process helped us to identify, classify, review, and revise possible domains, questions, and response options. The final items for field testing include 26 questions or observations that a nurse assesses before, during, and after routine care time and feeding. Conclusions We successfully created a prototype scale using modified PROMIS methodology. This process can serve as a model for the development of proxy-reported outcomes scales in other pediatric populations.

Introduction: The incidence of chronic lung disease (CLD) varies among groups defined by their early pattern of respiratory disease.Methods: The study examined data collected prospectively on 1204 of the 1506 infants born in 2002-2004 at 23-27 weeks gestation who survived to 36 weeks post-menstrual age. Based on their initial respiratory presentation and need for supplemental oxygen during the first 2 weeks, infants were classified as having early and persistent pulmonary dysfunction (EPPD), early recovery of pulmonary function followed by deterioration (PD) or consistently good pulmonary function characterised by low FiO(2) (Low FiO(2)).Results: CLD was diagnosed in 69% of infants with EPPD, 52% with PD, and 17% in the Low FiO(2) group. Birth weight z score <-1 conveyed information about CLD risk in all three groups and was the major risk factor for infants in the Low FiO(2) group (OR 27; 95% CI 7 to 95). Mechanical ventilation at 7 days was associated with increased risk in the PD (OR 4.2, 95% CI 2.5 to 6.9) and EPPD groups (OR 2.7, 95% CI 1.5 to 4.7), but not the Low FiO(2) group (OR 1.5, 95% CI 0.5 to 3.9).Conclusion: The likelihood of a very preterm infant developing CLD and the profile of risk factors linked with CLD are related to the infant's pattern of respiratory disease during the first 2 postnatal weeks. Among infants with little exposure to oxygen during this period, fetal growth restriction, not mechanical ventilation, is the factor with the strongest association with CLD. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To evaluate the relationships among cerebral palsy (CP) phenotypes and bronchopulmonary dysplasia (BPD) severity and, in the process, to generate hypotheses regarding causal pathways linking BPD to CP. STUDY DESIGN: We studied 1047 infants born before the 28th week of gestation. Receipt of supplemental oxygen at 36 weeks postmenstrual age (PMA), with or without the need for mechanical ventilation (MV) at 36 weeks PMA, defined two levels of BPD. At 24 months, the children underwent neurologic examinations and CP diagnoses were made using an algorithm based on topographic localisation. RESULTS: The 536 infants with BPD were at increased risk of all three CP phenotypes. In time-oriented multivariable analyses that adjusted for potential confounders, receipt of supplemental oxygen without MV at 36 weeks PMA (BPD) was not associated with increased risk of any CP phenotype. In contrast, BPD accompanied by MV at 36 weeks PMA (BPD/MV) was associated with a nearly sixfold increased risk of quadriparesis and a fourfold increased risk of diparesis. CONCLUSIONS: Combined treatment with both MV and supplemental oxygen at 36 weeks PMA strongly predicts the more common bilateral CP phenotypes. BPD without MV at 36 weeks PMA was not significantly associated with any form of CP. [ABSTRACT FROM AUTHOR]

BACKGROUND Bronchopulmonary dysplasia is a prevalent complication after extremely preterm debirth. Inflammation with mechanical ventilation may contribute to its development. Whether hydrocortisone treatment after the second postnatal week can improve survival without bronchopulmonary dysplasia and without adverse neuro-developmental effects is unknown. METHODS We conducted a trial involving infants who had a gestational age of less than 30 weeks and who had been intubated for at least 7 days at 14 to 28 days. Infants were randomly assigned to receive either hydrocortisone (4 mg per kilogram of body weight per day tai)ered over a period of 10 days) or placebo. Mandatory extuba-investigation thresholds were specified. The primary efficacy outcome was survival without moderate or severe bronchopulmonary dysplasia at 36 weeks of postmenstrual age, and the primary safety outcome was survival without moderate or severe neuro-developmental impairment at 22 to 26 months of corrected age. RESULTS We enrolled 800 infants (mean [iSD] birth weight, 715+167 g; mean gestational age, 24.911.5 weeks). Survival without moderate or severe bronchopulmonary dysplasia at 36 weeks occurred in 66 of 398 infants (16.6%) in the hydrocortisone group and in 53 of 402 (13.2°/o) in the placebo group (adjusted rate ratio, 1.27; 95% confidence interval [CI], 0.93 to 1.74). Two-year outcomes were known for 91.0% of the infants. Survival without moderate or severe neurodevelopmental impairment occurred in 132 of 358 infants (36.9°6) in the hydrocortisone group and in 134 of 359 (37.3°6) in the placebo group (adjusted rate ratio, 0.98; 95% CI, 0.81 to 1.18). Hypertension that was treated with medication occurred more frequently with hydrocortisone than with placebo (4.3% vs. 1.090). Other adverse events were similar in the two groups. CONCLUSIONS In this trial involving preterm infants, hydrocortisone treatment starting on postnatal day 14 to 28 did not result in substantially higher survival without moderate or severe bronchopulmonary dysplasia than placebo. Survival without moderate or severe neurodevelopmental impairment did not differ substantially between the two groups. [ABSTRACT FROM AUTHOR]

Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest. This workshop and summary are supported by the Food and Drug Administration (FDA) of the U.S. Department of Health and Human Services (HHS) as part of a financial assistance award [U19FD006602] totaling $4,241,714 with 100 percent funded by FDA/HHS. The contents are those of the author(s) and do not necessarily represent the official views of, nor an endorsement, by FDA/HHS, or the U.S. Government.

Objective: Our objective was to examine changes in the use of indomethacin prophylaxis in the neonatal intensive care unit (NICU) between 2008 and 2018., Study Design: The design of the study included cohort of 19,715 infants born between 22 0/7 and 26 6/7 weeks' gestation from 213 NICUs. A nonparametric trend test evaluated indomethacin prophylaxis and the percentage of sites using any prophylaxis over time. We evaluated the prevalence of indomethacin prophylaxis by the center and the correlation between indomethacin prophylaxis and severe intraventricular hemorrhage prevalence among 12 centers with the largest relative change in indomethacin prophylaxis prevalence., Results: In total, 16% of infants received indomethacin prophylaxis. The use of indomethacin prophylaxis did not significantly decrease between 2008 and 2018 but it significantly decreased between 2014 and 2018 ( p  = 0.046). Among 74 centers with ≥10 infants included, 20% increased the use of indomethacin prophylaxis, while 57% decreased the use over the study period. Of the 12 centers with the largest relative change in indomethacin prophylaxis prevalence, 50% showed an inverse correlation between indomethacin prophylaxis prevalence and severe intraventricular hemorrhage, while 50% showed a positive correlation., Conclusion: Receipt of indomethacin prophylaxis remained similar until 2014, decreased from 2014 to 2018, and varied by the center.Key Points · The receipt of indomethacin prophylaxis decreased over time.. · Center change in the use of indomethacin prophylaxis does not correlate with the center prevalence of IVH.. · Variability in the use of indomethacin prophylaxis across centers persists.., Competing Interests: R.G.G. reports consulting services for Tellus Therapeutics. The other authors have no conflicts of interest to disclose., (Thieme. All rights reserved.)