Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Patent ductus arteriosus shunt elimination results in a reduction in adverse outcomes: a post hoc analysis of the PDA RCT cohort



A post hoc appraisal of the PDA RCT to assess the relationship between early patent ductus arteriosus (PDA) shunt elimination and chronic lung disease or death (CLD/Death).

Study design

Infants <29 weeks were divided into four groups: intervention arm in whom PDA closure was achieved (n = 17); intervention arm in whom PDA closure was not achieved (n = 13); placebo arm (n = 30); low risk infants (n = 13). The main outcome measure was CLD/Death.


The rates of CLD/Death were lower in the Intervention Success Group (29%) when compared to the Intervention Failure Group (85%) or the Placebo Group (60%, all p < 0.05). There was no difference in CLD/Death between the Intervention Success and Low Risk Groups (8%, p > 0.05). A persistent PDA beyond Day 8 was associated with CLD/Death (aOR 6.5 [1.7–25.5]).


Early shunt elimination in preterm infants with a PDA may reduce respiratory morbidity when compared to infants with prolonged shunt exposure.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Get just this article for as long as you need it


Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Patent ductus arteriosus characteristics between infants with an open duct beyond day 8 (red line) and infants with a closed duct by day 8 (blue line).

Availability of data and materials

Data will be kept confidential in compliance with the European General Data Protection Regulation.


  1. El-Khuffash A, James AT, Corcoran JD, Dicker P, Franklin O, Elsayed YN, et al. A patent ductus arteriosus severity score predicts chronic lung disease or death before discharge. J Pediatr. 2015;167:1354–1361 e1352.

    Article  Google Scholar 

  2. Sellmer A, Bjerre JV, Schmidt MR, McNamara PJ, Hjortdal VE, Host B, et al. Morbidity and mortality in preterm neonates with patent ductus arteriosus on day 3. Arch Dis Child Fetal Neonatal Ed. 2013;98:F505–F510.

    Article  Google Scholar 

  3. Fink D, El-Khuffash A, McNamara PJ, Nitzan I, Hammerman C. Tale of two patent ductus arteriosus severity scores: similarities and differences. Am J Perinatol. 2018;35:55–58.

    Article  Google Scholar 

  4. Benitz WE. Treatment of persistent patent ductus arteriosus in preterm infants: time to accept the null hypothesis? J Perinatol. 2010;30:241–52.

    Article  CAS  Google Scholar 

  5. El-Khuffash A, Levy PT, Gorenflo M, Frantz ID III. The definition of a hemodynamically significant ductus arteriosus. Pediatr Res. 2019;85:740–1.

    Article  Google Scholar 

  6. Smith A, El-Khuffash AF. Defining “haemodynamic significance” of the patent ductus arteriosus: do we have all the answers? Neonatology. 2020;117:225–32.

    Article  Google Scholar 

  7. El-Khuffash A, Bussmann N, Breatnach CR, Smith A, Tully E, Griffin J, et al. A pilot randomized controlled trial of early targeted patent ductus arteriosus treatment using a Risk Based Severity Score (The PDA RCT). J Pediatr. 2021;229:127–33.

    Article  CAS  Google Scholar 

  8. Bancalari E, Claure N. Definitions and diagnostic criteria for bronchopulmonary dysplasia. Semin Perinatol. 2006;30:164–70.

    Article  Google Scholar 

  9. Papile LA, Burstein J, Burstein R, Koffler H. Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm. J Pediatr. 1978;92:529–34.

    Article  CAS  Google Scholar 

  10. Bell MJ. Neonatal necrotizing enterocolitis. N. Engl J Med. 1978;298:281–2.

    Article  CAS  Google Scholar 

  11. de Boode WP, Singh Y, Gupta S, Austin T, Bohlin K, Dempsey E, et al. Recommendations for neonatologist performed echocardiography in Europe: Consensus Statement endorsed by European Society for Paediatric Research (ESPR) and European Society for Neonatology (ESN). Pediatr Res. 2016;80:465–71.

    Article  Google Scholar 

  12. Nestaas E, Schubert U, de Boode WP, El-Khuffash A.European Special Interest Group “Neonatologist Performed Echocardiography" Tissue Doppler velocity imaging and event timings in neonates: a guide to image acquisition, measurement, interpretation, and reference values. Pediatr Res. 2018;84(Suppl 1):S18–S29.

    Article  Google Scholar 

  13. van Laere D, van Overmeire B, Gupta S, El-Khuffash A, Savoia M, McNamara PJ, et al. Application of NPE in the assessment of a patent ductus arteriosus. Pediatr Res. 2018;84(Suppl 1):S46–S56.

    Article  Google Scholar 

  14. Groves AM, Singh Y, Dempsey E, Molnar Z, Austin T, El-Khuffash A, et al. Introduction to neonatologist-performed echocardiography. Pediatr Res. 2018;84(Suppl 1):S1–S12.

    Article  Google Scholar 

  15. El-Khuffash A, Schubert U, Levy PT, Nestaas E, de Boode WP.European Special Interest Group “Neonatologist Performed Echocardiography Deformation imaging and rotational mechanics in neonates: a guide to image acquisition, measurement, interpretation, and reference values. Pediatr Res. 2018;84(Suppl 1):S30–S45.

    Article  Google Scholar 

  16. Smith A, Maguire M, Livingstone V, Dempsey EM. Peak systolic to end diastolic flow velocity ratio is associated with ductal patency in infants below 32 weeks of gestation. Arch Dis Child Fetal Neonatal Ed. 2015;100:F132–F136.

    Article  CAS  Google Scholar 

  17. Evans N. Preterm patent ductus arteriosus: a continuing conundrum for the neonatologist? Semin Fetal Neonatal Med. 2015;20:272–7.

    Article  Google Scholar 

  18. Chang LY, McCurnin D, Yoder B, Shaul PW, Clyman RI. Ductus arteriosus ligation and alveolar growth in preterm baboons with a patent ductus arteriosus. Pediatr Res. 2008;63:299–302.

    Article  Google Scholar 

  19. Kluckow M, Jeffery M, Gill A, Evans N. A randomised placebo-controlled trial of early treatment of the patent ductus arteriosus. Arch Dis Child Fetal Neonatal Ed. 2014;99:F99–F104.

    Article  Google Scholar 

  20. Clyman RI, Liebowitz M, Kaempf J, Erdeve O, Bulbul A, Hakansson S, et al. PDA-TOLERATE trial: an exploratory randomized controlled trial of treatment of moderate-to-large patent ductus arteriosus at 1 week of age. J Pediatr. 2019;205:41–48 e46.

    Article  Google Scholar 

  21. Liebowitz M, Katheria A, Sauberan J, Singh J, Nelson K, Hassinger DC, et al. Lack of equipoise in the PDA-TOLERATE trial: a comparison of eligible infants enrolled in the trial and those treated outside the trial. J Pediatr. 2019;213:222–226 e222.

    Article  Google Scholar 

  22. Mitra S, Florez ID, Tamayo ME, Mbuagbaw L, Vanniyasingam T, Veroniki AA, et al. Association of placebo, indomethacin, ibuprofen, and acetaminophen with closure of hemodynamically significant patent ductus arteriosus in preterm infants: a systematic review and meta-analysis. JAMA. 2018;319:1221–38.

    Article  CAS  Google Scholar 

  23. Lago P, Salvadori S, Opocher F, Ricato S, Chiandetti L, Frigo AC. Continuous infusion of ibuprofen for treatment of patent ductus arteriosus in very low birth weight infants. Neonatology. 2014;105:46–54.

    Article  CAS  Google Scholar 

  24. Mitra S, Scrivens A, von Kursell AM, Disher T. Early treatment versus expectant management of hemodynamically significant patent ductus arteriosus for preterm infants. Cochrane Datab Syst Rev. 2020;12:CD013278.

    Google Scholar 

Download references


This study was funded by a research grant from the Temple Street Hospital Foundation (Ref: RPAC 16-03). The National Children’s Research Centre funded Ph.D. fees associated with this project.

Author information

Authors and Affiliations



AEL-K and PMcN devised the study protocol and analysis plan, which was approved by all the authors, and provided oversight for the conduct of the trial. NB recruited the patients, performed the blinded echocardiography analysis and data collection. CB and AS assisted in patient recruitment and echocardiography studies. NMcC provided expert neonatal oversight. BC provided oversight of drug preparation and administration. OF provided cardiology expertise. All the listed authors made substantial contributions to either the conception or design of the work, or the acquisition, analysis, or interpretation of data for the work. NB wrote the first draft but all the listed authors revised it critically for important intellectual content, approve the final version of the manuscript and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Corresponding author

Correspondence to Afif EL-Khuffash.

Ethics declarations

Conflict of interest

The authors declare no competing interest.

Ethical approval and consent to participate

Ethical approval was obtained from our institutional ethics board (The National Maternity Hospital, Reference Number: EC 09.2016) and written informed consent was obtained from all parents. The study was performed in accordance with the Declaration of Helsinki.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Trial Registration: The trial was registered with the ISRCTN (13281214) and the European Union Drug Regulating Authorities Clinical Trials Database (2015-004526-33).

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bussmann, N., Smith, A., Breatnach, C.R. et al. Patent ductus arteriosus shunt elimination results in a reduction in adverse outcomes: a post hoc analysis of the PDA RCT cohort. J Perinatol 41, 1134–1141 (2021).

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


Quick links