Rationale: Benefits of identifying risk factors for bronchopulmonary dysplasia in extremely premature infants include providing prognostic information, identifying infants likely to benefit from preventive strategies, and stratifying infants for clinical trial enrollment. Objectives: To identify risk factors for bronchopulmonary dysplasia, and the competing outcome of death, by postnatal day; to identify which risk factors improve prediction; and to develop a Web-based estimator using readily available clinical information to predict risk of bronchopulmonary dysplasia or death. Measurements and Main Results: Bronchopulmonary dysplasia was defined as a categorical variable (none, mild, moderate, or severe). We developed and validated models for bronchopulmonary dysplasia risk at six postnatal ages using gestational age, birth weight, race and ethnicity, sex, respiratory support, and FI O 2 , and examined the models using a C statistic (area under the curve). A total of 3,636 infants were eligible for this study. Prediction improved with advancing postnatal age, increasing from a C statistic of 0.793 on Day 1 to a maximum of 0.854 on Day 28. On Postnatal Days 1 and 3, gestational age best improved outcome prediction; on Postnatal Days 7, 14, 21, and 28, type of respiratory support did so. A Web-based model providing predicted estimates for bronchopulmonary dysplasia by postnatal day is available at https://neonatal.rti.org. Conclusions: The probability of bronchopulmonary dysplasia in extremely premature infants can be determined accurately using a limited amount of readily available clinical information.Keywords: bronchopulmonary dysplasia; prematurity; low-birth-weight infant AT A GLANCE COMMENTARY Scientific Knowledge on the SubjectBronchopulmonary dysplasia is the most common serious pulmonary morbidity in premature infants. Although accurate predictive models of bronchopulmonary dysplasia risk are sometimes used in research, none are currently used in common clinical practice for a variety of reasons. What This Study Adds to the FieldIn this study, we identified the change in the relative contributions of a variety of risk factors to the prediction of bronchopulmonary dysplasia with advancing postnatal age. This tool may help identify patients most likely to benefit from postnatal treatment and assist in the design of clinical trials to assess the efficacy of preventive therapies in high-risk populations.

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.

Pulmonary surfactant, a lipoprotein complex, is essential for normal lung function, and deficiency of surfactant can result in respiratory-distress syndrome (RDS) in the prematurely born infant. Some studies have pointed towards a genetic contribution to the aetiology of RDS. Because the surfactant protein B (SP-B) is important for optimal surfactant function and because it is involved in the pathogenesis of pulmonary disease, we investigated the genetic variability of the SP-B gene in individuals with and without RDS. We identified a 2.5 kb BamHI polymorphism and studied its location, nature and frequency. We localized this polymorphism in the first half of intron 4 and found that it is derived by gain or loss in the number of copies of a motif that consists of two elements, a 20 bp conserved sequence and a variable number of CA dinucleotides. Variability in the number of motifs resulting from either deletion (in 55.3% of the cases with the variation) or insertion (44.7%) of motifs was observed in genomic DNAs from unrelated individuals. Analysis of 219 genomic DNAs from infants with (n = 82) and without (n = 137) RDS showed that this insertion/deletion appears with significantly higher frequency in the RDS population (29.3 as against 16.8%, P < 0.05).

In this cluster-randomized trial, benchmarking and multimodal quality improvement changed practices but did not reduce bronchopulmonary dysplasia rates.

Prescription of oxygen with combinations of flow rates and oxygen concentrations that delivered a low effective FIO2 was common. We speculate that some of this, including the inadvertent prescription of an effective FIO2 equivalent to that of room air, is related to lack of knowledge of the effective FIO2. Routine calculation of effective FIO2 values may prompt earlier trials of room air and thus reduce unnecessary days of oxygen therapy.