Social Determinants of Health and Timing of Tracheostomy for Severe Bronchopulmonary Dysplasia.

OBJECTIVE: To estimate the association of ZIP code-level social determinants of health (SDoH), specifically household income, education level, and unemployment rate, with post-menstrual age (PMA) at tracheostomy placement in patients with severe bronchopulmonary dysplasia (BPD). STUDY DESIGN: This was a retrospective observational study of infants born <32 weeks' gestation and discharged from a Children's Hospitals Neonatal Consortium newborn intensive care unit. Patients were diagnosed with severe BPD and received tracheostomies before discharge. Maternal ZIP code at admission was linked to that ZIP code's SDoH via the 2021 US Census Bureau 5-year data. Unadjusted and adjusted analyses were completed with separate models fit for each SDoH marker. RESULTS: 877 patients received tracheostomies at median (interquartile) 48 (44-53) weeks' PMA. In multivariable models, patients in the highest education groups received tracheostomies earlier (OR: 95% CI = 0.972: 0.947-0.997, p=0.031), and non-Hispanic Black patients received tracheostomies later compared with non-Hispanic White patients (OR: 1.026; 95% CI =1.005-1.048, p=0.017). For household income and unemployment, the PMA at tracheostomy did not differ by SDoH or race. For all three models, male sex, small for gestation status, and later PMA at admission were associated with later PMA at tracheostomy. For each SDoH marker, significant inter-center variation was noted as several centers had independently increased PMA at tracheostomy. CONCLUSIONS: Education at the ZIP code-level influenced PMA at tracheostomy after adjusting for patient and clinical factors. Adjusted for each SDoH studied, significant differences were noted among centers. Factors leading to the decision and timing of neonatal tracheostomy need further evaluation.

Surfactant treatment at birth in a contemporary cohort of preterm infants with bronchopulmonary dysplasia.

OBJECTIVE: Initial surfactant studies demonstrated improvements in survival and need for respiratory support. However, as the use of non-invasive respiratory support has increased the use of surfactant has decreased. We examined in a contemporary cohort of BPD patients if surfactant use was associated with BPD severity. STUDY DESIGN: An observational study using data from the BPD Collaborative Registry. RESULTS: 971 infants with BPD met entry criteria, 864 (89%) had received surfactant in the first 72 h of life (SURF) and the remainder had not (no surfactant). There was an association between SURF and BPD grade, with a greater likelihood of grade 3 BPD in infants who received surfactant in the DR or who had 2 or more doses. CONCLUSIONS: We speculate that the use of surfactant in the DR and use of multiple doses reflect the impact of perinatal factors beyond immaturity alone that increase the risk for grade 3 BPD.

Interdisciplinary clinical bronchopulmonary dysplasia programs: development, evolution, and maturation.

Multidisciplinary bronchopulmonary dysplasia (BPD) programs provide improved and consistent medical management, care of the developing infant, family support, and smoother transitions in care resulting in improved survival, pulmonary, and extra-pulmonary outcomes. This review summarizes the benefits of interdisciplinary BPD management, as well as strategies for initial programmatic development, program growth, and maintenance at centers across the United States factoring in institutional, provider, and parent reported goals that were derived from a consensus conference on BPD management.

Childhood outcomes following discharge from a referral bronchopulmonary dysplasia program.

OBJECTIVES: The primary objective of this study was to profile the childhood health, development, and health-related quality of life (HR QoL) for children with the most severe bronchopulmonary dysplasia (BPD), those discharged from a quaternary referral program. STUDY DESIGN: We collected cross-sectional data through telephone interviews with 282 families of children ages 18 months to 11 years who had been discharged from a BPD referral program. RESULTS: Respiratory morbidities were near universal, with 42% of children ever having required a tracheostomy and severity of these morbidities correlated with parent-reported health and QoL. Developmental morbidities were also marked: 97% required an individualized educational plan. While respiratory morbidities and overall health improved over time, developmental morbidities were increasingly prominent, resulting in lower quality of life. CONCLUSIONS: Among children referred to a quaternary BPD program, respiratory and developmental morbidities are on numerous counts more severe than any reported in the literature.

Managing established bronchopulmonary dysplasia without using routine blood gas measurements.

OBJECTIVE: Routine blood gas measurements are common in infants with severe bronchopulmonary dysplasia (sBPD) and are a noxious stimulus. We developed a guideline-driven approach to evaluate the care of infants with sBPD without routine blood gas sampling in the chronic phase of NICU care (after diagnosis at 36 weeks PMA). STUDY DESIGN: We examined blood gas utilization and outcomes in our sBPD inpatient care unit using data collected between 2014 and 2020. RESULTS: 485 sBPD infants met inclusion criteria, and 303 (62%) never had a blood gas obtained after 36 weeks PMA. In infants who had blood gas measurements, the median number of total blood gases per patient was only 4 (IQR 1-10). We did not identify adverse effects on hospital outcomes in patients without routine blood gas measurements. CONCLUSIONS: We found that patients with established BPD could be managed without routine blood gas analyses after 36 weeks PMA.

Transpyloric feeding is associated with adverse in-hospital outcomes in infants with severe bronchopulmonary dysplasia.

OBJECTIVE: To estimate the association of transpyloric feeding (TPF) with the composite outcome of tracheostomy or death for patients with severe bronchopulmonary dysplasia (sBPD). STUDY DESIGN: Retrospective multi-center cohort study of preterm infants <32 weeks with sBPD receiving enteral feedings. We compared infants who received TPF at 36, 44, or 50 weeks post-menstrual age to those who did not receive TPF at any of those timepoints. Odds ratios were adjusted for gestational age, small for gestational age, male sex, and invasive ventilation and FiO2 at 36 weeks. RESULTS: Among 1039 patients, 129 (12%) received TPF. TPF was associated with an increased odds of tracheostomy or death (aOR 3.5, 95% CI 2.0-6.1) and prolonged length of stay or death (aOR 3.1, 95% CI 1.9-5.2). CONCLUSIONS: Use of TPF in sBPD after 36 weeks was infrequent and associated with worse in-hospital outcomes, even after adjusting for respiratory severity at 36 weeks.

Association of the respiratory severity score with bronchopulmonary dysplasia-associated pulmonary hypertension in infants born extremely preterm.

OBJECTIVE: To test the hypothesis that elevations in the respiratory severity score (RSS) are associated with increased probability of bronchopulmonary dysplasia-associated pulmonary hypertension (BPD-PH). STUDY DESIGN: Retrospective cohort study of infants born extremely preterm admitted to a BPD center between 2010 and 2018. Echocardiograms obtained ≥ 36 weeks' post-menstrual age (PMA) were independently adjudicated by two blinded cardiologists to determine the presence/absence of BPD-PH. Multivariable logistic regression estimated the association between RSS and BPD-PH. RESULT: BPD-PH was observed in 68/223 (36%) of subjects. The median RSS at time of echocardiography was 3.04 (Range 0-18.3). A one-point increase in the RSS was associated with BPD-PH, aOR 1.3 (95% CI 1.2-1.4), after adjustment for gestational age and PMA at time of echocardiography. CONCLUSION: Elevations in the RSS were associated with a greater probability of BPD-PH. Prospective studies are needed to determine the validity and performance of RSS as a clinical susceptibility/risk biomarker for BPD-PH.

Exploring the Association of Male Sex With Adverse Outcomes in Severe Bronchopulmonary Dysplasia: A Retrospective, Multicenter Cohort Study.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a significant contributor to morbidity and death in infants who are born premature. Male sex is an independent risk factor for the development of BPD. However, whether male sex is associated with adverse outcomes that occur after formal diagnosis of severe BPD prior to hospital discharge remains unclear. RESEARCH QUESTION: Is male sex associated with a higher risk of adverse outcomes in infants with established severe BPD? STUDY DESIGN AND METHODS: A retrospective, multicenter cohort study of infants enrolled in the BPD Collaborative Registry from January 1, 2015, to June 29, 2022, was performed. Demographics, clinical characteristics, and outcomes were stratified by sex (ie, male vs female). Regression modeling was used to estimate the association of sex with the primary composite outcome of death or tracheostomy at hospital discharge. RESULTS: We identified 1,156 infants with severe BPD, defined at 36 weeks postmenstrual age by the National Institutes of Health 2001 consensus definition. The cohort was predominantly male (59% male infants, 41% female infants). However, rates of mechanical ventilation at 36 weeks postmenstrual age (ie, type 2 severe BPD) did not differ by sex. Overall mortality rates within the cohort were low (male infants, 5.3%; female infants, 3.6%). The OR of death or tracheostomy for male-to-female infants was 1.0 (95% CI, 0.7-1.5). INTERPRETATION: Our results lead us to speculate that, although sex is an important variable that contributes to the development and pathogenesis of severe BPD, it does not appear to be associated with adverse outcomes in this cohort of infants with established disease. The surprising results raise important questions surrounding the temporal role of biological sex in the development of severe BPD and its progression during the neonatal ICU stay. As we explore the phenotypes and endotypes of BPD, it is imperative to consider how sex modulates the disease from birth through hospital discharge.

Nutritional Needs of the Infant with Bronchopulmonary Dysplasia.

Growth failure is a common problem in infants with established bronchopulmonary dysplasia (BPD). Suboptimal growth for infants with BPD is associated with unfavorable respiratory and neurodevelopmental outcomes; however, high-quality evidence to support best nutritional practices are limited for this vulnerable patient population. Consequently, there exists a wide variation in the provision of nutritional care and monitoring of growth for infants with BPD. Other neonatal populations at risk for growth failure, such as infants with congenital heart disease, have demonstrated improved growth outcomes with the creation and compliance of clinical protocols to guide nutritional management. Developing clinical protocols to guide nutritional management for infants with BPD may similarly improve long-term outcomes. Given the absence of high-quality trials to guide nutritional practice in infants with BPD, the best available evidence of systematic reviews and clinical recommendations can be applied to optimize growth and decrease variation in the care of these infants.

To Trach or Not To Trach: Long-term Tracheostomy Outcomes in Infants with BPD.

See Bonus NeoBriefs videos and downloadable teaching slides Infants born preterm who are diagnosed with bronchopulmonary dysplasia (BPD) demonstrate a wide spectrum of illness severity. For infants with the most severe forms of BPD, safe discharge from the hospital may only be possible by providing long-term ventilation via a surgically placed tracheostomy. Though tracheostomy placement in infants with BPD is infrequent, recent reports suggest that rates of tracheostomy placement are increasing in this population. Even though there are known respiratory and neurodevelopmental risks associated with tracheostomy placement, no evidence-based criteria or consensus clinical practice guidelines exist to inform tracheostomy placement in this growing and vulnerable population. An incomplete knowledge of long-term post-tracheostomy outcomes in infants with BPD may unduly bias medical decision-making and family counseling regarding tracheostomy placement. This review aims to summarize our current knowledge of the epidemiology and long-term outcomes of tracheostomy placement in infants with BPD to provide a family-centered framework for tracheostomy counseling.

Short-course antibiotic therapy for pneumonia in the neonatal intensive care unit.

OBJECTIVE: To determine the adherence and safety outcomes of a 5-day antibiotic course with a "time-out" for treatment of "blood culture-negative" pneumonia in the NICU. STUDY DESIGN: Prospective surveillance of all infants diagnosed with pneumonia at 7 NICUs from 8/2020-12/2021. Safety outcomes were defined a priori by re-initiation of antibiotic therapy within 14 days after discontinuation and overall and sepsis-related mortality. RESULTS: 128 infants were diagnosed with 136 episodes of pneumonia; 88% (n = 119) were treated with 5 days of definitive antibiotic therapy. Antibiotics were restarted within 14 days in 22 (16%) of the 136 pneumonia episodes. However, only 3 (3%) of the 119 episodes of pneumonia treated for 5 days had antibiotics restarted for pneumonia. Mortality was 5% (7/128); 5 of the 7 deaths were assessed as sepsis-related. CONCLUSION: Adherence to the 5-day definitive antibiotic treatment for "culture-negative" pneumonia was high and the intervention seemed safe.

Classifying multicenter approaches to invasive mechanical ventilation for infants with bronchopulmonary dysplasia using hierarchical clustering analysis.

INTRODUCTION: Evidence-based ventilation strategies for infants with severe bronchopulmonary dysplasia (BPD) remain unknown. Determining whether contemporary ventilation approaches cluster as specific BPD strategies may better characterize care and enhance the design of clinical trials. The objective of this study was to test the hypothesis that unsupervised, multifactorial clustering analysis of point prevalence ventilator setting data would classify a discrete number of physiology-based approaches to mechanical ventilation in a multicenter cohort of infants with severe BPD. METHODS: We performed a secondary analysis of a multicenter point prevalence study of infants with severe BPD treated with invasive mechanical ventilation. We clustered the cohort by mean airway pressure (MAP), positive end expiratory pressure (PEEP), set respiratory rate, and inspiratory time (Ti) using Ward's hierarchical clustering analysis (HCA). RESULTS: Seventy-eight patients with severe BPD were included from 14 centers. HCA classified three discrete clusters as determined by an agglomerative coefficient of 0.97. Cluster stability was relatively strong as determined by Jaccard coefficient means of 0.79, 0.85, and 0.77 for clusters 1, 2, and 3, respectively. The median PEEP, MAP, rate, Ti, and PIP differed significantly between clusters for each comparison by Kruskall-Wallis testing (p < 0.0001). CONCLUSIONS: In this study, unsupervised clustering analysis of ventilator setting data identified three discrete approaches to mechanical ventilation in a multicenter cohort of infants with severe BPD. Prospective trials are needed to determine whether these approaches to mechanical ventilation are associated with specific severe BPD clinical phenotypes and differentially modify respiratory outcomes.

Ranking Future Outcomes Most Important to Parents of Children with Bronchopulmonary Dysplasia.

OBJECTIVE: To assess which potential future outcomes are most important to parents of children with bronchopulmonary dysplasia, a disease that affects future respiratory, medical, and developmental outcomes for children born preterm. STUDY DESIGN: We recruited parents from 2 children's hospitals' neonatal follow-up clinics and elicited their importance rating for 20 different potential future outcomes associated with bronchopulmonary dysplasia. These outcomes were identified and selected through a literature review and discussions with panels of parents and clinician stakeholders, via a discrete choice experiment. RESULTS: One hundred and 5 parents participated. Overall, parents ranked "Will my child be more vulnerable to other problems because of having lung disease?" as the most important outcome, with other respiratory health related outcomes also highly ranked. Outcomes related to child development and effects on the family were among the lowest ranked. Individually, parents rated outcomes differently, resulting in a broad distribution of importance scores for many of the outcomes. CONCLUSIONS: The overall rankings suggest that parents prioritize future outcomes related to physical health and safety. Notably, for guiding research, some top-rated outcomes are not traditionally measured in outcome studies. For guiding individual counseling, the broad distribution of importance scores for many outcomes highlights the extent to which parents differ in their prioritization of outcomes.

A review and guide to nutritional care of the infant with established bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) remains the most common long-term morbidity of premature birth, and the incidence of BPD is not declining despite medical advancements. Infants with BPD are at high risk for postnatal growth failure and are often treated with therapies that suppress growth. Additionally, these infants may display excess weight gain relative to linear growth. Optimal growth and nutrition are needed to promote lung growth and repair, improve long-term pulmonary function, and improve neurodevelopmental outcomes. Linear growth in particular has been associated with favorable outcomes yet can be difficult to achieve in these patients. While there has been a significant clinical and research focus regarding BPD prevention and early preterm nutrition, there is a lack of literature regarding nutritional care of the infant with established BPD. There is even less information regarding how nutritional needs change as BPD evolves from an acute to chronic disease. This article reviews the current literature regarding nutritional challenges, enteral nutrition management, and monitoring for patients with established BPD. Additionally, this article provides a practical framework for interdisciplinary nutritional care based on our clinical experience at the Comprehensive Center for Bronchopulmonary Dysplasia.

Association of Racial Disparities With In-Hospital Outcomes in Severe Bronchopulmonary Dysplasia.

Importance: Bronchopulmonary dysplasia (BPD) is the most common serious morbidity of preterm birth. Short-term respiratory outcomes for infants with the most severe forms of BPD are highly variable. The mechanisms that explain this variability remain unknown and may be mediated by racial disparities. Objective: To determine the association of maternal race with death and length of hospital stay in a multicenter cohort of infants with severe BPD. Design, Setting, and Participants: This multicenter cohort study included preterm infants enrolled in the BPD Collaborative registry from January 1, 2015, to July 19, 2021, involving 8 BPD Collaborative centers located in the US. Included patients were born at less than 32 weeks' gestation, had a diagnosis of severe BPD as defined by the 2001 National Institutes of Health Consensus Criteria, and were born to Black or White mothers. Exposures: Maternal race: Black vs White. Main Outcomes and Measures: Death and length of hospital stay. Results: Among 834 registry infants (median [IQR] gestational age, 25 [24-27] weeks; 492 male infants [59%]) meeting inclusion criteria, the majority were born to White mothers (558 [67%]). Death was observed infrequently in the study cohort (32 [4%]), but Black maternal race was associated with an increased odds of death (adjusted odds ratio, 2.1; 95% CI, 1.2-3.5) after adjusting for center. Black maternal race was also significantly associated with length of hospital stay (adjusted between-group difference, 10 days; 95% CI, 3-17 days). Conclusions and Relevance: In a multicenter severe BPD cohort, study results suggest that infants born to Black mothers had increased likelihood of death and increased length of hospital stay compared with infants born to White mothers. Prospective studies are needed to define the sociodemographic mechanisms underlying disparate health outcomes for Black infants with severe BPD.

Bronchodilator responsiveness and dysanapsis in bronchopulmonary dysplasia.

Background: The incidence of bronchopulmonary dysplasia (BPD) following preterm birth is increasing. Bronchodilators are often used to treat patients with BPD with little evidence to guide therapy. The aim of this study was to test the hypothesis that there are infant pulmonary function test (iPFT) parameters that can predict subsequent bronchodilator response in infants with BPD. Methods: Subjects in this study were part of a patient group in which we reported three BPD phenotypes (obstructive, restrictive and mixed) based on iPFT data. From that group, a cohort of 93 patients with iPFT data including bronchodilator response was eligible for this study. Results: Bronchodilator responsiveness was found in 59 people (63%) in the cohort. There were no differences in demographics between the responders and non-responders. There was no difference in forced vital capacity (FVC) between the two groups. Responders had significantly lower forced expiratory volume in 0.5 s (FEV0.5) and FEV0.5/FVC (p<0.005) and greater indices of hyperinflation than did non-responders (p<0.005). Logistic regression modelling found that pre-bronchodilator FEV0.5 and functional residual capacity/total lung capacity were significantly associated with bronchodilator response. The magnitude of response to bronchodilators was negatively correlated (R= -0.49, R2= 0.24, p<0.001) with the FEV0.5. The median dysanapsis ratio in responders (0.08, 95% CI 0.05-0.19) was significantly (p=0.005) smaller than in non-responders (0.18, 95% CI 0.06-0.38). Conclusion: These findings demonstrate that there are pulmonary function test parameters associated with bronchodilator response. Responders had evidence of greater dysanaptic lung growth than non-responders.