Health Care Utilization During the COVID-19 Pandemic Among Individuals Born Preterm.

Importance: Limited data exist on pediatric health care utilization during the COVID-19 pandemic among children and young adults born preterm. Objective: To investigate differences in health care use related to COVID-19 concerns during the pandemic among children and young adults born preterm vs those born at term. Design, Setting, and Participants: In this cohort study, questionnaires regarding COVID-19 and health care utilization were completed by 1691 mother-offspring pairs from 42 pediatric cohorts in the National Institutes of Health Environmental Influences on Child Health Outcomes Program. Children and young adults (ages 1-18 years) in these analyses were born between 2003 and 2021. Data were recorded by the August 31, 2021, data-lock date and were analyzed between October 2021 and October 2022. Exposures: Premature birth (<37 weeks' gestation). Main Outcomes and Measures: The main outcome was health care utilization related to COVID-19 concerns (hospitalization, in-person clinic or emergency department visit, phone or telehealth evaluations). Individuals born preterm vs term (≥37 weeks' gestation) and differences among preterm subgroups of individuals (<28 weeks', 28-36 weeks' vs ≥37 weeks' gestation) were assessed. Generalized estimating equations assessed population odds for health care used and related symptoms, controlling for maternal age, education, and psychiatric disorder; offspring history of bronchopulmonary dysplasia (BPD) or asthma; and timing and age at COVID-19 questionnaire completion. Results: Data from 1691 children and young adults were analyzed; among 270 individuals born preterm, the mean (SD) age at survey completion was 8.8 (4.4) years, 151 (55.9%) were male, and 193 (71.5%) had a history of BPD or asthma diagnosis. Among 1421 comparison individuals with term birth, the mean (SD) age at survey completion was 8.4 (2.4) years, 749 (52.7%) were male, and 233 (16.4%) had a history of BPD or asthma. Preterm subgroups included 159 individuals (58.5%) born at less than 28 weeks' gestation. In adjusted analyses, individuals born preterm had a significantly higher odds of health care utilization related to COVID-19 concerns (adjusted odds ratio [aOR], 1.70; 95% CI, 1.21-2.38) compared with term-born individuals; similar differences were also seen for the subgroup of individuals born at less than 28 weeks' gestation (aOR, 2.15; 95% CI, 1.40-3.29). Maternal history of a psychiatric disorder was a significant covariate associated with health care utilization for all individuals (aOR, 1.44; 95% CI, 1.17-1.78). Conclusions and Relevance: These findings suggest that during the COVID-19 pandemic, children and young adults born preterm were more likely to have used health care related to COVID-19 concerns compared with their term-born peers, independent of a history of BPD or asthma. Further exploration of factors associated with COVID-19-related health care use may facilitate refinement of care models.

Acceptability of COVID-19 vaccination in Chinese children aged 3-7 years with bronchopulmonary dysplasia.

OBJECTIVES: To describe the status of coronavirus disease 2019 (COVID-19) vaccination with inactivated vaccines BBIBP-CorV and CoronaVac in Chinese children aged 3-7 years with bronchopulmonary dysplasia (BPD), and explore factors influencing vaccination and reasons for nonvaccination. METHODS: This cross-sectional study involving parents of 397 BPD children aged 3-7 years was conducted through WeChat or follow-up telephone interviews using a standardized questionnaire form. Factors influencing COVID-19 vaccination were explored by using modified Poisson regression models. RESULTS: The overall COVID-19 vaccination rate was 69.0% (95% confidence interval: 64.3%-73.4%). COVID-19 vaccination was less likely to be accepted in children whose mothers had a relatively high educational background (university and above), who lived in urban areas and had a low birth weight (<1 kg), a history of hospitalization for lung diseases in the past 12 months, and intellectual disability. Conversely, kindergarten students and children from families with an annual income of >300,000 CNY ( ≈ $\approx $ 41,400 USD) were more likely to accept vaccination. Adverse reactions occurred in 13/274 children (4.7%) within 10 days after vaccination. With respect to reasons of not accepting COVID-19 vaccination, 95 parents (77.2%) worried about the adverse reactions, and 17 parents (13.8%) refused vaccination on the excuse of not being convenient to go to the vaccination station or not knowing where to get the vaccines. CONCLUSIONS: The COVID-19 vaccination rate in BPD children aged 3-7 years needs to be further improved in China. Continuous efforts are required to monitor postvaccination adverse reactions in BPD children, and make vaccination more convenient and accessible.

Early severity prediction of BPD for premature infants from chest X-ray images using deep learning: A study at the 28th day of oxygen inhalation.

BACKGROUND AND OBJECTIVE: Bronchopulmonary dysplasia is a common respiratory disease in premature infants. The severity is diagnosed at the 56th day after birth or discharge by analyzing the clinical indicators, which may cause the delay of the best treatment opportunity. Thus, we proposed a deep learning-based method using chest X-ray images of the 28th day of oxygen inhalation for the early severity prediction of bronchopulmonary dysplasia in clinic. METHODS: We first adopted a two-step lung field extraction method by combining digital image processing and human-computer interaction to form the one-to-one corresponding image and label. The designed XSEG-Net model was then trained for segmenting the chest X-ray images, with the results being used for the analysis of heart development and clinical severity. Therein, Six-Point cardiothoracic ratio measurement algorithm based on corner detection was designed for the analysis of heart development; and the transfer learning of deep convolutional neural network models were used for the early prediction of clinical severities. RESULTS: The dice and cross-entropy loss value of the training of XSEG-Net network reached 0.9794 and 0.0146. The dice, volumetric overlap error, relative volume difference, precision, and recall were used to evaluate the trained model in testing set with the result being 98.43 ± 0.39%, 0.49 ± 0.35%, 0.49 ± 0.35%, 98.67 ± 0.40%, and 98.20 ± 0.47%, respectively. The errors between the Six-Point cardiothoracic ratio measurement method and the gold standard were 0.0122 ± 0.0084. The deep convolutional neural network model based on VGGNet had the promising prediction performance, with the accuracy, precision, sensitivity, specificity, and F1 score reaching 95.58 ± 0.48%, 95.61 ± 0.55%, 95.67 ± 0.44%, 96.98 ± 0.42%, and 95.61±0.48%, respectively. CONCLUSIONS: These experimental results of the proposed methods in lung field segmentation, cardiothoracic ratio measurement and clinic severity prediction were better than previous methods, which proved that this method had great potential for clinical application.

Nasal continuous positive airway pressure levels for the prevention of morbidity and mortality in preterm infants.

BACKGROUND: Preterm infants are at risk of lung atelectasis due to various anatomical and physiological immaturities, placing them at high risk of respiratory failure and associated harms. Nasal continuous positive airway pressure (CPAP) is a positive pressure applied to the airways via the nares. It helps prevent atelectasis and supports adequate gas exchange in spontaneously breathing infants. Nasal CPAP is used in the care of preterm infants around the world. Despite its common use, the appropriate pressure levels to apply during nasal CPAP use remain uncertain. OBJECTIVES: To assess the effects of 'low' (≤ 5 cm H2O) versus 'moderate-high' (> 5 cm H2O) initial nasal CPAP pressure levels in preterm infants receiving CPAP either: 1) for initial respiratory support after birth and neonatal resuscitation or 2) following mechanical ventilation and endotracheal extubation. SEARCH METHODS: We ran a comprehensive search on 6 November 2020 in the following databases: CENTRAL via CRS Web and MEDLINE via Ovid. We also searched clinical trials databases and the reference lists of retrieved articles for randomized controlled trials (RCTs) and quasi-randomized trials. SELECTION CRITERIA: We included RCTs, quasi-RCTs, cluster-RCTs and cross-over RCTs randomizing preterm infants of gestational age < 37 weeks or birth weight < 2500 grams within the first 28 days of life to different nasal CPAP levels. DATA COLLECTION AND ANALYSIS: We used the standard methods of Cochrane Neonatal to collect and analyze data. We used the GRADE approach to assess the certainty of the evidence for the prespecified primary outcomes. MAIN RESULTS: Eleven trials met inclusion criteria of the review. Four trials were parallel-group RCTs reporting our prespecified primary or secondary outcomes. Two trials randomized 316 infants to low versus moderate-high nasal CPAP for initial respiratory support, and two trials randomized 117 infants to low versus moderate-high nasal CPAP following endotracheal extubation. The remaining seven studies were cross-over trials reporting short-term physiological outcomes. The most common potential sources of bias were absent or unclear blinding of personnel and assessors and uncertain selective reporting. Nasal CPAP for initial respiratory support after birth and neonatal resuscitation None of the six primary outcomes prespecified for inclusion in the summary of findings was eligible for meta-analysis. No trials reported on moderate-severe neurodevelopmental impairment at 18 to 26 months. The remaining five outcomes were reported in a single trial. On the basis of this trial, we are uncertain whether low or moderate-high nasal CPAP levels improve the outcomes of: death or bronchopulmonary dysplasia (BPD) at 36 weeks' postmenstrual age (PMA) (risk ratio (RR) 1.02, 95% confidence interval (CI) 0.56 to 1.85; 1 trial, 271 participants); mortality by hospital discharge (RR 1.04, 95% CI 0.51 to 2.12; 1 trial, 271 participants); BPD at 28 days of age (RR 1.10, 95% CI 0.56 to 2.17; 1 trial, 271 participants); BPD at 36 weeks' PMA (RR 0.80, 95% CI 0.25 to 2.57; 1 trial, 271 participants), and treatment failure or need for mechanical ventilation (RR 1.00, 95% CI 0.63 to 1.57; 1 trial, 271 participants). We assessed the certainty of the evidence as very low for all five outcomes due to risk of bias, a lack of consistency across multiple studies, and imprecise effect estimates. Nasal CPAP following mechanical ventilation and endotracheal extubation One of the six primary outcomes prespecified for inclusion in the summary of findings was eligible for meta-analysis. On the basis of these data, we are uncertain whether low or moderate-high nasal CPAP levels improve the outcome of treatment failure or need for mechanical ventilation (RR 1.52, 95% CI 0.92 to 2.50; 2 trials, 117 participants; I2 = 17%; risk difference 0.15, 95% CI -0.02 to 0.32; number needed to treat for an additional beneficial outcome 7, 95% CI -50 to 3). We assessed the certainty of the evidence as very low due to risk of bias, inconsistency across the studies, and imprecise effect estimates. No trials reported on moderate-severe neurodevelopmental impairment at 18 to 26 months or BPD at 28 days of age. The remaining three outcomes were reported in a single trial. On the basis of this trial, we are uncertain whether low or moderate-high nasal CPAP levels improve the outcomes of: death or BPD at 36 weeks' PMA (RR 0.87, 95% CI 0.51 to 1.49; 1 trial, 93 participants); mortality by hospital discharge (RR 2.94, 95% CI 0.12 to 70.30; 1 trial, 93 participants), and BPD at 36 weeks' PMA (RR 0.87, 95% CI 0.51 to 1.49; 1 trial, 93 participants). We assessed the certainty of the evidence as very low for all three outcomes due to risk of bias, a lack of consistency across multiple studies, and imprecise effect estimates.  AUTHORS' CONCLUSIONS: There are insufficient data from randomized trials to guide nasal CPAP level selection in preterm infants, whether provided as initial respiratory support or following extubation from invasive mechanical ventilation. We are uncertain as to whether low or moderate-high nasal CPAP levels improve morbidity and mortality in preterm infants. Well-designed trials evaluating this important aspect of a commonly used neonatal therapy are needed.

Risk factors for severe COVID-19 in hospitalized children in Canada: A national prospective study from March 2020--May 2021 (preprint)

Background: Children living with chronic comorbid conditions are at increased risk for severe COVID-19, though there is limited evidence regarding the risks associated with specific conditions and which children may benefit from targeted COVID-19 therapies. The objective of this study was to identify factors associated with severe disease among hospitalized children with COVID-19 in Canada. Methods: We conducted a national prospective study on hospitalized children with microbiologically confirmed SARS-CoV-2 infection via the Canadian Paediatric Surveillance Program from April 2020--May 2021. Cases were reported voluntarily by a network of >2800 paediatricians. Hospitalizations were classified as COVID-19-related, incidental infection, or infection control/social admissions. Severe disease (among COVID-19-related hospitalizations only) was defined as disease requiring intensive care, ventilatory or hemodynamic support, select organ system complications, or death. Risk factors for severe disease were identified using multivariable Poisson regression, adjusting for age, sex, concomitant infections, and timing of hospitalization. Findings: We identified 544 children hospitalized with SARS-CoV-2 infection, including 60{middle dot}7% with COVID-19-related disease and 39{middle dot}3% with incidental infection or infection control/social admissions. Among COVID-19-related hospitalizations (n=330), the median age was 1{middle dot}9 years (IQR 0{middle dot}1--13{middle dot}3) and 43{middle dot}0% had chronic comorbid conditions. Severe disease occurred in 29{middle dot}7% of COVID-19-related hospitalizations (n=98/330), most frequently among children aged 2-4 years (48{middle dot}7%) and 12-17 years (41{middle dot}3%). Comorbid conditions associated with severe disease included technology dependence (adjusted risk ratio [aRR] 2{middle dot}01, 95% confidence interval [CI] 1{middle dot}37-2{middle dot}95), neurologic conditions (e.g. epilepsy and select chromosomal/genetic conditions) (aRR 1{middle dot}84, 95% CI 1{middle dot}32-2{middle dot}57), and pulmonary conditions (e.g. bronchopulmonary dysplasia and uncontrolled asthma) (aRR 1{middle dot}63, 95% CI 1{middle dot}12-2{middle dot}39). Interpretation: While severe outcomes were detected at all ages and among patients with and without comorbidities, neurologic and pulmonary conditions as well as technology dependence were associated with increased risk of severe COVID-19. These findings may help guide vaccination programs and prioritize targeted COVID-19 therapies for children. Funding: Financial support for the CPSP was received from the Public Health Agency of Canada.

Face mask versus nasal prong or nasopharyngeal tube for neonatal resuscitation in the delivery room: a systematic review and meta-analysis.

IMPORTANCE: The current neonatal resuscitation guidelines recommend positive pressure ventilation via face mask or nasal prongs at birth. Using a nasal interface may have the potential to improve outcomes for newborn infants. OBJECTIVE: To determine whether nasal prong/nasopharyngeal tube versus face mask during positive pressure ventilation of infants born <37 weeks' gestation in the delivery room reduces in-hospital mortality and morbidity. DATA SOURCES: MEDLINE (through PubMed), Google Scholar and EMBASE, Clinical Trials.gov and the Cochrane Central Register of Controlled Trials through August 2019. STUDY SELECTION: Randomised controlled trials comparing nasal prong/nasopharyngeal tube versus face mask during positive pressure ventilation of infants born <37 weeks' gestation in the delivery room. DATA ANALYSIS: Risk of bias was assessed using the Covidence Collaboration Tool, results were pooled into a meta-analysis using a random effects model. MAIN OUTCOME: In-hospital mortality. RESULTS: Five RCTs enrolling 873 infants were combined into a meta-analysis. There was no statistical difference in in-hospital mortality (risk ratio (RR 0.98, 95% CI 0.63 to 1.52, p=0.92, I2=11%), rate of chest compressions in the delivery room (RR 0.37, 95% CI 0.10 to 1.33, p=0.13, I2=28%), rate of intraventricular haemorrhage (RR 1.54, 95% CI 0.88 to 2.70, p=0.13, I2=0%) or delivery room intubations in infants ventilated with a nasal prong/tube (RR 0.63, 95% CI 0.39,1.02, p=0.06, I2=52%). CONCLUSION: In infants born <37 weeks' gestation, in-hospital mortality and morbidity were similar following positive pressure ventilation during initial stabilisation with a nasal prong/tube or a face mask.

In-hospital respiratory viral infections for patients with established BPD in the SARS-CoV-2 era.

OBJECTIVE: Our objective was to test the hypothesis that in-hospital respiratory viral infections (RVI) would be significantly lower in a cohort of patients with established bronchopulmonary dysplasia (BPD) exposed to a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection prevention protocol when compared to historical controls. STUDY DESIGN: On April 1, 2020, we implemented a universal infection prevention protocol to minimize the risk of nosocomial SARS-CoV-2 transmission in a dedicated BPD intensive care unit. We performed a retrospective cohort study and included patients with established BPD, as defined by the 2019 Neonatal Research Network criteria, admitted to our center who underwent real-time polymerase-chain-reaction RVI testing between January 1, 2015 and March 31, 2021. We excluded patients readmitted from home. We compared the proportion of positive tests to the number of tests performed and the distribution of viral respiratory pathogens in the pre- and post-SARS-CoV-2 eras. RESULTS: Among 176 patients included in the study, 663 RVI tests were performed and 172 (26%) tests were positive. The median number of tests performed, measured in tests per patient per month, in the SARS-CoV-2 era was not significantly different compared to the pre-SARS-CoV-2 era (0.45 vs. 0.34 tests per patient per month, p = .07). The proportion of positive RVI tests was significantly lower in the SARS-CoV-2 era when compared to the pre-SARS-CoV-2 era (0.06 vs. 0.30, p < .0001). No patients tested positive for SARS-CoV-2 in the SARS-CoV-2 era. CONCLUSIONS: Infection prevention measures developed in response to the SARS-CoV-2 pandemic may reduce the risk of RVIs in hospitalized patients with established BPD.

Mesenchymal stem cells from different sources show distinct therapeutic effects in hyperoxia-induced bronchopulmonary dysplasia in rats.

Mesenchymal stem cells (MSCs) have been shown as an effective medicinal means to treat bronchopulmonary dysplasia (BPD). The widely used MSCs were from Wharton's jelly of umbilical cord (UC-MSCs) and bone marrow (BM-MSCs). Amniotic fluid MSCs (AF-MSCs) may be produced before an individual is born to treat foetal diseases by autoplastic transplantation. We evaluated intratracheal (IT) MSCs as an approach to treat an hyperoxia-induced BPD animal model and compared the therapeutic effects between AF-, UC- and BM-MSCs. A BPD animal model was generated by exposing newborn rats to 95% O2 . The continued stress lasted 21 days, and the treatment of IT MSCs was conducted for 4 days. The therapeutic effects were analysed, including lung histology, level of inflammatory cytokines, cell death ratio and state of angiogenesis, by sacrificing the experimental animal at day 21. The lasting hyperoxia stress induced BPD similar to the biological phenotype. The treatment of IT MSCs was safe without deaths and normal organ histopathology. Specifically, the treatment was effective by inhibiting the alveolar dilatation, reducing inflammatory cytokines, inducing angiogenesis and lowering the cell death ratio. AF-MSCs had better therapeutic effects compared with UC-MSCs in relieving the pulmonary alveoli histological changes and promoting neovascularization, and UC-MSCs had the best immunosuppressive effect in plasma and lung lysis compared with AF-MSCs and BM-MSCs. This study demonstrated the therapeutic effects of AF-, UC- and BM-MSCs in BPD model. Superior treatment effect was provided by antenatal MSCs compared to BM-MSC in a statistical comparison.

Air quality, Environment and Respiratory Outcomes in Bronchopulmonary Dysplasia, the AERO-BPD cohort study: design and adaptation during the SARS-CoV-2 pandemic.

INTRODUCTION: Almost half of all school-age children with bronchopulmonary dysplasia (BPD) have asthma-like symptoms and more suffer from lung function deficits. While air pollution and indoor respiratory irritants are known to affect high-risk populations of children, few studies have objectively evaluated environmental contributions to long-term respiratory morbidity in this population. This study aimed to examine the role of indoor environmental exposures on respiratory morbidity in children with BPD. METHODS AND ANALYSIS: The Air quality, Environment and Respiratory Ouctomes in BPD (AERO-BPD) study is a prospective, single-centre observational study that will enrol a unique cohort of 240 children with BPD and carefully characterise participants and their indoor home environmental exposures. Measures of indoor air quality constituents will assess the relationship of nitrogen dioxide (NO2), particulate matter (PM2.5), nitric oxide (NO), temperature and humidity, as well as dust concentrations of allergens, with concurrently measured respiratory symptoms and lung function.Adaptations to the research protocol due to the SARS-CoV-2 pandemic included remote home environment and participant assessments. ETHICS AND DISSEMINATION: Study protocol was approved by the Boston Children's Hospital Committee on Clinical Investigation. Dissemination will be in the form of peer-reviewed publications and participant information products. TRIAL REGISTRATION NUMBER: NCT04107701.

The Spectrum of COVID-19 in Children in Spain (preprint)

Background: We aimed to identify the spectrum of disease in children with COVID-19, and the risk factors for admission in paediatric intensive care units (PICUs). Methods: : We conducted a multicentre, prospective study of children with SARS-CoV-2 infection in 76 Spanish hospitals. We included children with COVID-19 or multi-inflammatory syndrome (MIS-C) younger than 18 years old, attended during the first year of the pandemic. Results: We enrolled 1 200 children. A total of 666 (55.5%) were hospitalized, and 123 (18.4%) required admission to PICU. Most frequent major clinical syndromes in the cohort were: mild syndrome (including upper respiratory tract infection and flu-like syndrome, skin or mucosae problems and asymptomatic), 44.8%; bronchopulmonary syndrome (including pneumonia, bronchitis and asthma flare), 18.5%; fever without a source, 16.2%; MIS-C, 10.6%; and gastrointestinal syndrome, 10%. In hospitalized children, the proportions were: 28.5%, 25.7%, 16.5%, 19.1% and 10.2%, respectively. Risk factors associated with PICU admission were MIS-C (odds ratio [OR]: 37.5,95% CI 22.7 to 57.8), moderate or severe liver disease (OR: 9,95% CI 1.6 to 47.6), chronic cardiac disease (OR: 4.8,95% CI 1.8 to 13) and asthma or recurrent wheezing (OR: 2.8,95% CI 1.3 to 5.8). However, asthmatic children were admitted into the PICU due to MIS-C or pneumonia, not due to asthma flare. Conclusion: Hospitalized children with COVID-19 usually present as one of five major clinical phenotypes of decreasing severity. Risk factors for PICU include MIS-C, elevation of inflammation biomarkers, asthma, moderate or severe liver disease and cardiac disease.

In-Hospital Respiratory Viral Infections for Patients with Established BPD in the SARS-CoV-2 Era (preprint)

Objective: Our objective was to test the hypothesis that in-hospital respiratory viral infections (RVI) would be significantly lower in a cohort of patients with established bronchopulmonary dysplasia in the SARS-CoV-2 era when compared to historical controls. Study Design On April 1, 2020, we implemented a universal infection prevention bundle to minimize the risk of nosocomial SARS-CoV-2 transmission in a dedicated BPD intensive care unit. We performed a retrospective cohort study and included patients with established BPD, as defined by the 2019 Neonatal Research Network criteria, admitted to our center who underwent real-time polymerase-chain-reaction RVI testing between January 1, 2015 and March 31, 2021. We excluded patients re-admitted from home. We compared to number of tests performed, the proportion of positive tests, and the distribution of viral respiratory pathogens in the pre- and post-SARS-CoV-2 eras. Results Among 176 patients included in the sudy, 663 RVI tests were performed and 172 (26%) tests were positive. The median number of tests performed, measured in tests per patient per month, in the SARS-CoV-2 era was not significantly different compared to the pre-SARS-CoV-2 era (0.45 vs 0.34 tests per patient per month, P = 0.07). The proportion of positive RVI tests was significantly lower in the SARS-CoV-2 era when compared to the pre-SARS-CoV-2 era (0.06 vs 0.30, P<0.0001). No patients tested positive for SARS-CoV-2 in the SARS-CoV-2 era. Conclusions Infection prevention measures developed in response to the SARS-CoV-2 pandemic may reduce the risk of RVIs in hospitalized patients with established BPD.

Benefits and obstacles to cell therapy in neonates: The INCuBAToR (Innovative Neonatal Cellular Therapy for Bronchopulmonary Dysplasia: Accelerating Translation of Research).

Cell-based therapies hold promise to substantially curb complications from extreme preterm birth, the main cause of death in children below the age of 5 years. Exciting preclinical studies in experimental neonatal lung injury have provided the impetus for the initiation of early phase clinical trials in extreme preterm infants at risk of developing bronchopulmonary dysplasia. Clinical translation of promising therapies, however, is slow and often fails. In the adult population, results of clinical trials so far have not matched the enticing preclinical data. The neonatal field has experienced many hard-earned lessons with the implementation of oxygen therapy or postnatal steroids. Here we briefly summarize the preclinical data that have permitted the initiation of early phase clinical trials of cell-based therapies in extreme preterm infants and describe the INCuBAToR concept (Innovative Neonatal Cellular Therapy for Bronchopulmonary Dysplasia: Accelerating Translation of Research), an evidence-based approach to mitigate the risk of translating advanced therapies into this vulnerable patient population. The INCuBAToR addresses several of the shortcomings at the preclinical and the clinical stage that usually contribute to the failure of clinical translation through (a) systematic reviews of preclinical and clinical studies, (b) integrated knowledge transfer through engaging important stakeholders early on, (c) early economic evaluation to determine if a novel therapy is viable, and (d) retrospective and prospective studies to define and test ideal eligibility criteria to optimize clinical trial design. The INCuBAToR concept can be applied to any novel therapy in order to enhance the likelihood of success of clinical translation in a timely, transparent, rigorous, and evidence-based fashion.

Current evidence for prenatal and postnatal corticosteroids in preterm infants.

Antenatal corticosteroids undoubtedly save many lives and improve the quality of many others. However, the currently accepted dosage schedule has been in place since 1972, and recent studies have suggested that beneficial effects may be seen with less. Most but not all studies of long-term outcome show no adverse effects. The use of antenatal corticosteroids in women with COVID-19 raises important questions regarding potential risks and benefits. However, currently, most authorities recommend continuing according to published guidelines. With regard to postnatal corticosteroids, alternatives to systemic dexamethasone, the somewhat tainted standard of care, show promise in preventing bronchopulmonary dysplasia without adverse effects. Systemic hydrocortisone and inhaled corticosteroids are of note. The mixture of surfactant and corticosteroids deserves particular attention in the coming years.

Respiratory medication use in extremely premature (<29 weeks) infants during initial NICU hospitalization: Results from the prematurity and respiratory outcomes program.

BACKGROUND: The use of medications to treat respiratory conditions of extreme prematurity is often based upon studies of adults or children over 2 years of age. Little is known about the spectrum of medications used or dosing ranges. To inform the design of future studies, we conducted a prospective analysis of respiratory medication exposure among 832 extremely low gestational age neonates. METHODS: The prematurity and respiratory outcomes program (PROP) enrolled neonates less than 29-week gestation from 6 centers incorporating 13 clinical sites. We collected recorded daily "respiratory" medications given along with dosing information through 40-week postmenstrual age or neonatal intensive care unit discharge if earlier. RESULTS: PROP participants were exposed to a wide range of respiratory medications, often at doses beyond published recommendations. Nearly 50% received caffeine and furosemide beyond published recommendations for cumulative dose. Those who developed bronchopulmonary dysplasia were more likely to receive treatment with respiratory medications. However, more than 30% of PROP subjects that did not develop bronchopulmonary dysplasia also were treated with diuretics, systemic steroids, and other respiratory medications. CONCLUSION: Extremely preterm neonates in PROP were exposed to high doses of medications at levels known to generate significant adverse effects. With limited evidence for efficacy, there is an urgent need for controlled trials in this vulnerable patient population.