516 - Treatment of Bronchopulmonary Dysplasia (BPD): A Scoping Review of Interventional Trials

Publication Number: 1496.516

Maria B. Milet Letelier, Childrens Hospital of Philadelphia, Wynnewood, PA, United States; Ismail H. Bekiroglu, Lucile Packard Children's Hospital Stanford, San Carlos, CA, United States; Nicolas A. Bamat, Children's Hospital of Philadelphia, Swarthmore, PA, United States; Matthew Kielt, Nationwide Children's Hospital, Columbus, OH, United States; Laurie C. Eldredge, Seattle Children's, Seattle, WA, United States; Kathleen Gibbs, Childrens Hospital of Philadelphia, Philadelphia, PA, United States; Erik Jensen, Stanford University School of Medicine, Palo Alto, CA, United States

Background: Survival rates of preterm infants with established BPD have increased in recent decades, but comprehensive, systematic reviews of interventional trials performed in this population are lacking.

Objective: To describe the type and characteristics of published interventional trials that focus on treatment of established BPD.

Design/Methods: We performed a scoping review of published interventional trials conducted in infants with BPD indexed in PubMed from database inception to 4/4/2025. Two reviewers independently screened articles and abstracted data. We included randomized, pseudorandomized, or early phase trials among infants born < 37wk gestational age (GA) and/or < 1500g birth weight (BW), who were between 28d and 2yr of age at enrollment, and were diagnosed with BPD or receiving supplementary respiratory support at study entry. We excluded trials focused on BPD prevention, non-English publications, observational studies, editorials, reviews, and case reports.

Results: Our PubMed search yielded 6928 articles of which 66 trials met inclusion criteria (Fig 1). A total of 3,621 infants with BPD were enrolled (mean participant GA: 27.3wk, BW: 1,045g, chronological age at entry: 19.9wk [reported n=38 trials] or PMA: 38.1wks [reported n=21 trials]). Overall, 61% (n=40) were randomized trials, 67% (n=44) had a placebo/control, and 33% (n=22) were multicenter. The most frequent primary outcome was pulmonary function (n=26) determined by spirometry/airflow measurements. Trials reporting a drug/biologic therapy, nutritional intervention, or ventilation strategy were most common (Fig 2A). Most studies were published between 1979-99 (55%, n=36). The number of drug/biologic related trials decreased over time (Fig 2B). Among all drug/biologic trials, bronchodilators (17%) and diuretics (17%) accounted for the greatest number of distinct studies and most were published prior to 2000 (Fig 2C). Trials evaluating respiratory syncytial virus (RSV) monoclonal antibody accounted for the largest number of recruited infants (57%, n=2067, n= 4 trials) (Table 1). Among trials published after 2014 (n=11), 6 evaluated drug/biologic interventions, including 3 phase 1 trials of stem cells.

Conclusion(s): Despite increasing BPD rates and an urgent need for targeted therapies, trials focused on treatment of infants with established BPD have decreased in recent decades, with a particular decline in drug/biologic trials. Moreover, most trials were small, single center studies that measured only short-term outcomes. These results highlight a potential growing mismatch between BPD disease burden and research focused on BPD treatments.

Figure 1. Flow diagram of interventional trials focused on established BPD in preterm infants.


Figure 2. Types of interventions for established BPD published by category (Panel A), by category per decade (Panel B) and by drug per decade (Panel C), n (%).
*Steroid includes inhaled and systemic steroids. **Other drug includes: (1) heliox, (2) pulmonary vasodilator, (3) histamine receptor antagonist, (4) leukotriene receptor antagonist, and (5) peripheral chemoreceptor.

Table 1. Summary table. Types of interventions for established BPD by sample size, randomization and multicenter .
*Vaccines included: (1) Respiratory syncytial virus, (2) Haemophilus influenzae type b
**Other drug includes: (1) histamine receptor antagonist, (2) leukotriene receptor antagonist, and (3) peripheral chemoreceptor.