Skip to main content
Have a personal or library account? Click to login
Efficacy of ibuprofen versus acetaminophen and conservative management for closure of patent ductus arteriosus in preterm neonates: a randomized clinical trial Cover

Efficacy of ibuprofen versus acetaminophen and conservative management for closure of patent ductus arteriosus in preterm neonates: a randomized clinical trial

Open Access
|May 2026

References

  1. Noori NM, Teimouri A, Dehvari A, Bagheie S, Ansari H. The effect of oral acetaminophen on open arterial duct closure in premature infants less than 32 weeks. Romanian J Cardiol 2023; 33(2): 54-59. Available from URL: https://doi.org/10.2478/rjc-2023-0007
  2. Chatziantoniou A, Rorris F-P, Samanidis G, Kanakis M. Keeping the ductus arteriosus patent: Current strategy and perspectives. Diagnostics 2025; 15(3):241. Available from URL: https://doi.org/10.3390/diagnostics15030241
  3. Noori N, Yaghoubi S, Teimouri A. The evaluation of left atrial to aortic root diameter ratio after PDA closure in children. Int J Pediatr 2021; 9(11):14830-14841. DOI: 10.22038/IJP.2021.57769.4530
  4. Aguet J, Seed M, Marini D. Fetal cardiovascular magnetic resonance imaging. Pediatr Radiol 2020; 50:1881-94. Available from URL: https://doi.org/10.1007/s00247-020-04902-y
  5. Doherty TM, Hu A, Salik I. Physiology, Neonatal. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan [cited 2 Mar 2026]. Available from URL: https://www.ncbi.nlm.nih.gov/books/NBK539840/
  6. Spenard S, Backes C, Fitzgerald DA, Sant’Anna G, Altit G. Current approaches to the patent ductus arteriosus: implications for pulmonary morbidities. Paediatr Respir Rev 2025; S1526-0542(25)00057-0. doi: 10.1016/j.prrv.2025.05.001.
  7. Semberova J, Sirc J, Miletin J, Kucera J, Berka I, Sebkova S, et al. Spontaneous closure of patent ductus arteriosus in infants ≤ 1500 g. Pediatrics 2017; 140(2): e20164258. Available from URL: https://doi.org/10.1542/peds.2016-4258
  8. Philip R, Towbin JA, Sathanandam S, Goldberg J, Yohannan T, Swaminathan N, et al. Effect of patent ductus arteriosus on the heart in preterm infants. Congenit Heart Dis 2019; 14(1):33-6. Available from URL: https://doi.org/10.1111/chd.12701
  9. Mitra S, Jain A, Ting JY, Fadel NB, Drolet C, AbouMehrem A, et al, Dorling J. Relative effectiveness and safety of pharmacotherapeutic agents for patent ductus arteriosus (PDA) in preterm infants: a protocol for a multicentre comparative effectiveness study (CANRxPDA). BMJ Open 2021; 11(5):e050682. Available from URL: https://doi.org/10.1136/bmjopen-2021-050682
  10. Ahranjani B, Dalili H, Nashtifani Z, et al. The comparison between intravenous acetaminophen versus oral ibuprofen in preterm newborns with patent ductus arteriosus: aAclinical trial. Acta Med Iran 2021; 58(12):631-636.
  11. Aikio O, Härkin P, Saarela T, et al. Early paracetamol treatment associated with lowered risk of persistent ductus arteriosus in very preterm infants. J. Matern.-Fetal Neonatal Med 2014; 27(12):1252-6. Available from URL: https://doi.org/10.3109/14767058.2013.854327
  12. Terrin G, Conte F, Oncel MY, Scipione A, McNamara PJ, Simons S, et al. Paracetamol for the treatment of patent ductus arteriosus in preterm neonates: a systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed 2016; 101(2):F127-36. Available from URL: https://doi.org/10.1136/archdischild-2014-307312
  13. Härkin P, Härmä A, Aikio O, Valkama M, Leskinen M, Saarela T, et al. Paracetamol accelerates closure of the ductus arteriosus after premature birth: a randomized trial. J Pediatr 2016; 177:72-7. https://doi.org/10.1016/j. jpeds.2016.04.066
  14. Höck M, Brunner B, Rier V, Thöni S, Trawöger R, Geiger R, et al. Prophylactic low-dose paracetamol administration associated with lowered rate of patent ductus arteriosus in preterm infants-impact on outcome and pain perception. Pediatr Neonatol 2020; 61(1):84-91. Available from URL: https://doi.org/10.1016/j.pedneo.2019.06.011
  15. Dash SK, Kabra NS, Avasthi BS, Sharma SR, Padhi P, Ahmed J. Enteral paracetamol or intravenous indomethacin for closure of patent ductus arteriosus in preterm neonates: a randomized controlled trial. Indian Pediatr 2015; 52:573-8. Available from URL: https://doi.org/10.1007/s13312-015-0677-z
  16. Bagheri MM, Bahman-Bijari B, Torabi-Nejad MH, Niknafs P, Mousavi H, Sabzevari F, et al. Is prophylactic parenteral paracetamol effective to diminish incidence of PDA in preterm neonates? A randomized trial. Iran J Pediatr 2018; 28(4). Available from URL: https://doi.org/10.5812/ijp.11735
  17. Schindler T, Smyth J, Bolisetty S, Michalowski J, Mallitt KA, Singla A, et al. Early PARacetamol (EPAR) trial: A randomized controlled trial of early paracetamol to promote closure of the ductus arteriosus in preterm infants. Neonatology 2021; 118(3):274-81. Available from URL: https://doi.org/10.1159/000515415
  18. Surak A, Jain A and Hyderi A. Different approaches for patent ductus arteriosus in premature infants using acetaminophen. World J Pediatr 2022; 18:243-250. Available from URL: https://doi.org/10.1007/s12519-022-00526-4
  19. Iacobelli S, Lorrain S, Gouyon B, Gambacorta S, Laforgia N, Gouyon JB, et al. Drug exposure for PDA closure in France: a prospective, cohortbased, analysis. European J Clin Pharmacol 2020; 76:1765-72. Available from URL: https://doi.org/10.1007/s00228-020-02974-1
  20. Asbagh PA, Zarkesh MR, Nili F, Nayeri FS, Tofighi Naeem AT. Prophylactic treatment with oral paracetamol for patent ductus arteriosus in preterm infants: A randomized clinical trial. Tehran Univ Med J 2015; 73(2):86-92.
  21. Jasani B, Mitra S, Shah PS. Paracetamol (acetaminophen) for patent ductus arteriosus in preterm or low birth weight infants. Cochrane Database Syst Rev 2018(4). Available from URL: https://doi.org/10.1002/14651858. CD010061.pub5.
  22. Hillier K, Jones K, MacInnis M, Mitra S. Comparison of standard versus high-dose ibuprofen for the treatment of hemodynamically significant patent ductus arteriosus in preterm infants. J Perinatol 2021; 41(5):1142-1148. doi: 10.1038/s41372-021-01046-1.
  23. Dani C, Lista G, Bianchi S, Mosca F, Schena F, Ramenghi L, et al. Intravenous paracetamol in comparison with ibuprofen for the treatment of patent ductus arteriosus in preterm infants: A randomized controlled trial. Eur J Pediatr 2021; 180(3):807-16. Available from URL: https://doi.org/10.1007/s00431-020-03780-8
  24. Balachander B, Mondal N, Bhat V, Adhisivam B, Kumar M, Satheesh S, et al. Comparison of efficacy of oral paracetamol versus ibuprofen for PDA closure in preterms - a prospective randomized clinical trial. J Matern Fetal Neonatal Med 2020; 33(9):1587-92. Available from URL: https://doi.org/10.1080/14767058.2018.1525354
  25. Yang B, Gao X, Ren Y, Wang Y, Zhang Q. Oral paracetamol vs. oral ibuprofen in the treatment of symptomatic patent ductus arteriosus in premature infants: A randomized controlled trial. Exp Ther Med 2016; 12(4):2531-6. Available from URL: https://doi.org/10.3892/etm.2016.3676
  26. Oncel MY, Yurttutan S, Erdeve O, Uras N, Altug N, Oguz SS, et al. Oral paracetamol versus oral ibuprofen in the management of patent ductus arteriosus in preterm infants: a randomized controlled trial. J Pediatr 2014; 164(3):510-4. Available from URL: https://doi.org/10.1016/j.jpeds.2013.11.008
  27. Gonzalez-Luis G, Borges-Lujan M, Villamor E. Association between endotypes of prematurity and pharmacological closure of patent ductus arteriosus: A systematic review and meta-analysis. medRxiv 2022; 2022-10. Available from URL: https://doi.org/10.1101/2022.10.24.22281438
  28. Nemerofsky SL, Parravicini E, Bateman D, Kleinman C, Polin RA, Lorenz JM. The ductus arteriosus rarely requires treatment in infants > 1000 grams. Am J Perinatol 2008; 25(10):661-6. Available from URL: https://doi.org/10.1055/s-0028-1090594
  29. Herrman K, Bose C, Lewis K. Spontaneous closure of the patent ductus arteriosus in very low birth weight infants following discharge from the neonatal unit. Arch Dis Child Fetal Neonatal Ed 2009; 94(1):F48-50. Available from URL: https://doi.org/10.1136/adc.2007.129270
  30. Hamrick SE, Sallmon H, Rose AT, Porras D, Shelton EL, Reese J, et al. Patent ductus arteriosus of the preterm infant. Pediatrics 2020 Nov 1;146(5). Available from URL: https://doi.org/10.1542/peds.2020-1209
DOI: https://doi.org/10.2478/rjc-2026-0012 | Journal eISSN: 2734-6382 | Journal ISSN: 1220-658X
Language: English
Published on: May 29, 2026
In partnership with: Paradigm Publishing Services
Publication frequency: 4 issues per year

© 2026 Noor Mohammad Noori, Alireza Teimouri, Saeedeh Yaghoubi, published by Romanian Society of Cardiology
This work is licensed under the Creative Commons Attribution 4.0 License.

AHEAD OF PRINT