Bronchopulmonary dysplasia (BPD) is identified as a major complication of prematurity with limited available disease-modifying therapies. The reviewed work evaluated umbilical cord-derived cell-based interventions as potential therapies for BPD and related neonatal complications in preterm infants. The analysis followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidance and was registered in PROSPERO.
The authors searched PubMed, Cochrane Library, Web of Science, CNKI, and Wanfang from database inception through June 14, 2026. Eligible studies were comparative clinical studies that evaluated umbilical cord–derived cell-based interventions in preterm infants at risk of or diagnosed with BPD. Outcomes prespecified for extraction and synthesis included overall BPD, BPD severity categories, death, persistent pulmonary hypertension of the newborn (PPHN), patent ductus arteriosus (PDA), intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), late-onset sepsis (LOS), and adverse events (AEs).
For quantitative synthesis the investigators applied a Bayesian random-effects meta-analysis using a binomial-normal hierarchical model. Reported effect estimates were pooled odds ratios (ORs) with 95% credible intervals (CrIs). The analysis also produced prediction intervals and assessed heterogeneity. The approach was chosen to accommodate sparse data across outcomes.
Twelve studies met the inclusion criteria and were included in the meta-analysis. The PubMed abstract reports the total study count and outcome-level synthesis but does not provide further trial-level details such as participant numbers, gestational ages, exact intervention types per trial, dosing, timing, or comparator descriptions in the abstract. Those trial-level details were not reported in the source abstract and therefore are not summarized here.
Outcomes synthesized across studies included:
The pooled estimates from the Bayesian random-effects meta-analysis suggested possible and more certain effects for some endpoints:
Overall BPD: pooled OR 0.48 (95% CrI 0.14–1.20), indicating a possible protective association though the credible interval includes the null.
Severe BPD: pooled OR 0.17 (95% CrI 0.01–0.85), suggesting a stronger association in favor of umbilical cord-derived cell-based interventions for preventing severe BPD.
Moderate or severe BPD: pooled OR 0.28 (95% CrI 0.09–0.70), consistent with a protective effect for more clinically significant BPD categories.
Retinopathy of prematurity stage ≥3: pooled OR 0.17 (95% CrI 0.02–0.65), representing a potential additional benefit on advanced ROP.
For other outcomes including death, PPHN, PDA, IVH, NEC, and LOS, the meta-analysis did not identify conclusive benefit or harm. The authors also calculated prediction intervals and report that they were generally wide, reflecting uncertainty about the expected range of effect in future similar studies.
Across the included studies, no treatment-related serious adverse events were identified according to the abstract. The authors note this finding but temper it by describing the overall certainty of the safety estimates as limited by the available data.
The review found that the certainty of evidence was generally low to very low for most outcomes. The authors highlight wide prediction intervals for pooled estimates, meaning that effect sizes in future studies could plausibly vary substantially from the pooled estimates reported. This low certainty reflects sparse data and study limitations summarized in the source abstract.
Key limitations reported in the abstract include sparse data for many outcomes, wide prediction intervals, and low to very low certainty ratings for most endpoints. The abstract does not list detailed risk-of-bias assessments, individual study sizes, or follow-up durations; those trial-level details were not reported in the source abstract and therefore cannot be summarized here. Given these limitations, pooled estimates—especially for outcomes with wide CrIs—should be interpreted cautiously.
The meta-analysis indicates that umbilical cord-derived cell-based interventions may reduce the risk of moderate or severe BPD in preterm infants, with an additional potential benefit for ROP stage ≥3. No clear effects were demonstrated for death or several other major neonatal complications. No treatment-related serious adverse events were reported in the included studies. However, the overall evidence base is limited; the certainty of most findings was low to very low, and prediction intervals were wide. The authors conclude that larger randomized trials with standardized outcome definitions and long-term follow-up are needed to better define efficacy and safety.