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Dual medication therapy (acetaminophen and ibuprofen) for the management of patent ductus arteriosus in preterm infants: a systematic review and meta-analysis

Journal of Perinatology volume 42, pages 1654–1661 (2022)Cite this article

Subjects

Abstract

Objective

To examine the efficacy of dual medication therapy (intervention) (DMT: acetaminophen and ibuprofen) vs. single medication therapy (control) (SMT: ibuprofen) for medical management of PDA (outcomes) in preterm infants (population).

Study design

We systematically searched multiple sources to identify randomized controlled trials (RCT) and non-randomized studies (NRS) that compared DMT to SMT for management of hemodynamically significant PDA.

Results

We identified two RCTs and four NRS. There were no differences in the rates of successful PDA closure following the first treatment course between DMT and SMT (RR = 1.23 [95% CI 0.89–1.70] for NRS and RR = 1.18 [95% CI 0.66–2.10] for RCTs), nor were there significant differences in secondary outcomes and adverse events including PDA ligation, bronchopulmonary dysplasia, and necrotizing enterocolitis etc. Markers of hepatic/renal function did not change significantly during treatment.

Conclusion

We found no evidence for superiority of DMT over SMT in PDA management.

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Fig. 1
Fig. 2: Forest Plot of pooled effect estimates for successful PDA closure with DMT and SMT treatment.
Fig. 3: Forest Plot of pooled effect estimates for PDA ligation with DMT and SMT treatment.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Author information

Authors and Affiliations

  1. Division of Neonatology, Department of Pediatrics, University of Florida College of Medicine, Jacksonville, FL, USA

    Sanket D. Shah & Mark L. Hudak

  2. Division of Neonatology, Department of Pediatrics, Johns Hopkins Children’s Center, Johns Hopkins University, Baltimore, MD, USA

    Kartikeya Makker & Khyzer B. Aziz

  3. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA

    Mingyu Zhang

  4. Nemours Children’s Health, Jacksonville, FL, USA

    Susan Harnett

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Contributions

SS and KM conceptualized and designed the study, reviewed the literature, extracted the data for meta-analysis, performed the risk of bias assessment, wrote the initial draft of the manuscript and reviewed and revised the manuscript. MZ reviewed the literature, performed the risk of bias assessment, analyzed and interpret data, and critically reviewed the manuscript. SH performed an extensive literature search and reviewed the manuscript. KA designed the search strategy and critically reviewed and revised the manuscript. MLH conceptualized and designed the study and critically reviewed and revised the manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

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Correspondence to Sanket D. Shah.

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Shah, S.D., Makker, K., Zhang, M. et al. Dual medication therapy (acetaminophen and ibuprofen) for the management of patent ductus arteriosus in preterm infants: a systematic review and meta-analysis. J Perinatol 42, 1654–1661 (2022). https://doi.org/10.1038/s41372-022-01500-8

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