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  • Systematic Review
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Beneficial vs harmful effects of pharmacological treatment of patent ductus arteriosus: A Bayesian meta-analysis

Pediatric Research volume 98, pages 498–506 (2025)Cite this article

Abstract

Background

Randomized controlled trials (RCTs) have failed to demonstrate the beneficial effects of the pharmacological treatment of patent ductus arteriosus (PDA) in preterm infants. We conducted a Bayesian model averaged (BMA) meta-analysis of RCTs comparing the pharmacological treatment of PDA with placebo or expectant treatment.

Methods

We searched for RCTs including infants with gestational age (GA) ≤ 32 weeks and with a rate of open-label treatment of less than 25% in the control arm. The primary outcome was mortality and secondary outcomes included bronchopulmonary dysplasia (BPD). We calculated Bayes factors (BFs). The BF+/- is the ratio of the probability of the data under H+ (pharmacological treatment is beneficial) over the probability of the data under H- (pharmacological treatment is harmful).

Results

Five RCTs were included (1341 infants). BMA showed strong evidence in favor of the harmful effect of medication for BPD (BF+/- = 0.02) and BPD or death (BF+/- = 0.03). When the two largest trials, which used early (<72 h) ibuprofen in infants with GA ≤ 28 weeks, were pooled, the BMA demonstrated moderate evidence in favor of higher mortality in the medication group (BF+/- = 0.24).

Conclusion

Pharmacological treatment of PDA in extremely preterm infants may result in more complications than clinical benefit.

Impact

  • Randomized controlled trials spanning several decades have investigated the pharmacological treatment of patent ductus arteriosus (PDA) but have failed to demonstrate an improvement in mortality or short-term morbidity.

  • We conducted a Bayesian meta-analysis to answer the question: Is the pharmacological treatment of PDA beneficial or harmful in very and extremely preterm infants?

  • Bayesian meta-analysis showed strong evidence in favor of higher rates of bronchopulmonary dysplasia (BPD) and death or BPD in infants receiving pharmacological treatment of PDA when compared with infants receiving placebo or expectant management.

  • Pharmacological treatment of PDA in extremely preterm infants may result in more complications than clinical benefit.

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Fig. 1: Summary of Bayesian model average meta-analysis of dichotomous outcomes.
Fig. 2: Summary of Bayesian model average meta-analysis of continuous outcomes.
Fig. 3: Individual Bayesian analysis of the included studies.

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Data availability

All data relevant to the study are included in the article or uploaded as supplementary information.

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Funding

This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sectors.

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Authors and Affiliations

  1. Division of Neonatology, MosaKids Children’s Hospital, Maastricht University Medical Center (MUMC+), Research Institute for Oncology and Reproduction (GROW), Maastricht University, Maastricht, The Netherlands

    Eduardo Villamor

  2. Department of Pediatrics, Hospital Universitario Materno-Infantil de Canarias, Las Palmas de Gran Canaria, Spain

    Gloria Galán-Henríquez & Gema E. Gonzalez-Luis

  3. Department of Psychology, University of Amsterdam, Amsterdam, The Netherlands

    František Bartoš

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  1. Eduardo Villamor
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  2. Gloria Galán-Henríquez
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  3. František Bartoš
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  4. Gema E. Gonzalez-Luis
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Contributions

E.V. conceptualized and designed the study, performed the systematic search, coordinated and supervised data collection, drafted the initial manuscript, and critically reviewed and revised the manuscript. G.G.-H. and G.G.-L. designed the data collection instruments, collected data, and critically reviewed and revised the manuscript. F.B. designed and conducted the statistical analysis, and critically reviewed and revised the manuscript. All authors approved the final manuscript as submitted and agreed to be accountable for all aspects of the work.

Corresponding author

Correspondence to Eduardo Villamor.

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Competing interests

EV is co-author of one of the trials included in the meta-analysis. The other authors have no conflicts of interest to disclose.

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As this systematic review and meta-analysis did not involve animal subjects or personally identifiable information on human subjects, ethics review board approval and patient consent were not required.

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Villamor, E., Galán-Henríquez, G., Bartoš, F. et al. Beneficial vs harmful effects of pharmacological treatment of patent ductus arteriosus: A Bayesian meta-analysis. Pediatr Res 98, 498–506 (2025). https://doi.org/10.1038/s41390-025-03820-9

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