522 - Diuretics for Preventing Bronchopulmonary Dysplasia in Preterm Infants: A Systematic Review and Meta-Analysis

Publication Number: 3503.522

Shin Kato, Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital, Nagoya, Aichi, Japan; Masato Koizumi, Seirei Hamamatsu General Hospital/Division of Neonatology, Hamamatsu, Shizuoka, Japan; Jun Nirei, Niigata university, Niigata, Niigata, Japan; Katsuaki Honda, Seirei Hamamatsu General Hospital, Hamamatsu, Shizuoka, Japan; Akio Ishiguro, The University of Tokyo, Bunkyo-ku, Tokyo, Japan; Mutsumi Yamazaki, National Center for Child Health and Development, Setagaya-Ku, Tokyo, Japan; Tetsuya Isayama, National Center for Child Health and Development, Setagaya-ku, Tokyo, Japan

Background: Diuretics have long been used to improve respiratory mechanics and oxygenation in preterm infants with evolving bronchopulmonary dysplasia (BPD). Earlier randomized controlled trials (RCTs) reported short-term respiratory improvement but failed to prevent BPD. Although a recent phase II RCT mainly assessed safety, several observational studies have suggested possible benefits in preventing BPD, highlighting the need for an updated synthesis.

Objective: To evaluate the preventive effect and safety of diuretics on BPD in preterm infants with evolving BPD.

Design/Methods: We conducted a systematic review and meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement (PROSPERO CRD42022371299). Major databases (MEDLINE, Embase, CENTRAL, CINAHL) were searched up to June 2025 for RCTs and non-randomized studies. Risk of bias was assessed using the revised Cochrane Risk-of-Bias tool (RoB 2) and the Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I). Certainty of evidence was graded by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Random-effects models were applied when data were available, and risk ratios (RRs) with 95% confidence intervals (CIs) were calculated. Outcomes with insufficient data were summarized narratively.

Results: Forty studies, including six RCTs, were analyzed (Figure1, Table 1); furosemide was most frequently used. Most RCTs focused on short-term changes in lung mechanics and did not show preventive effects on BPD. The only recent RCT reported death or BPD with RR 1.10 (95% CI 0.77-1.59; low risk of bias). The meta-analyses showed favorable but nonsignificant effects of diuretics compared with controls for mortality (RR 0.44, 95% CI 0.19-1.04; three RCTs, n=201) and for extubation failure (RR 0.46, 95% CI 0.19-1.12; two RCTs, n=30). Electrolyte abnormalities were not different between diuretics and controls (RR 1.51, 95% CI, 0.81-2.83: two RCTs, n=138). Adverse events such as nephrocalcinosis or hearing impairment were reported in retrospective studies but not significant in the recent RCT. Several recent observational studies suggested a reduction of BPD. The certainty of evidence was low to very low due to small samples and heterogeneity (Figure 2).

Conclusion(s): Current evidence does not confirm a preventive effect of diuretics on BPD. However, favorable trends and reassuring safety findings from recent studies highlight the need for adequately powered RCTs to clarify their potential role in BPD prevention and long-term respiratory outcomes.

Figure 1. PRISMA Flow Diagram of Study Selection
Flow of study identification, screening, and inclusion according to the PRISMA 2020 statement.

Table 1. Summary of Included Studies
Overview of study design, population, interventions, and main outcomes of the included studies.

Figure 2. Evidence Profile (GRADE) and Representative Forest Plots of the Meta-analysis
Evidence Profile (GRADE) and Representative Forest Plots of the Meta-analysis (a) Summary of GRADE evidence for key outcomes comparing diuretics versus control in preterm infants (b) Comparison: Diuretics vs Control - Outcome 1: Death before Discharge (c) Comparison: Diuretics vs Control - Outcome 2: Extubation Failure (d) Comparison: Diuretics vs Control - Outcome 3: Hyponatremia