Efficacy of pharmacological treatment for closure of patent ductus arteriosus in preterm newborns: a systematic review
DOI:
https://doi.org/10.62486/sic2026299Keywords:
patent ductus arteriosus, pharmacological treatment, prematurity, efficacy, adverse effectsAbstract
Introduction: Patent ductus arteriosus (PDA) represents a relevant clinical problem due to its hemodynamic implications, especially in premature newborns, which has motivated multiple studies on its management. Currently, pharmacological treatment is one way to solve this problem, but there is no clear consensus as to which treatment is the most effective and least risky. Objective: The aim of this study was to find the drug with the highest rate of efficacy in PDA closure and with the least adverse effects. Methods: A descriptive systematic review was carried out following PRISMA guidelines. The search was carried out in SCOPUS, PUBMED, SCIELO, COCHRANE and LILACS databases. Results: After applying certain inclusion criteria, we obtained a total of 20 studies, most of which were systematic reviews and cohort studies. Among the studies reviewed, drugs such as indomethacin, ibuprofen, paracetamol and betamethasone have been used, finding that among the first three there is no statistically significant difference in efficacy. Closure rates and adverse effects vary considerably in the different studies, depending on factors such as dose, route of administration and gestational age of the neonate. Conclusions: The studies reviewed show that both ibuprofen and indomethacin have similar efficacy in PDA closure in preterm infants. Indomethacin is associated with higher risks of adverse effects. Acetaminophen appears to be a safe and effective alternative, with a superior safety profile compared to NSAIDs.
References
1. American Academy of Pediatrics. Libro de texto para la Reanimacion Neonatal [Internet]. 8.a ed. American Academy of PediatricsItasca, IL; 2022 [citado 5 de diciembre de 2024]. Disponible en: https://publications.aap.org/aapbooks/book/715/Libro-de-texto-para-la-Reanimacion-Neonatal
2. Linares Terrazas DÁ, Gomez Webber M. Conducto arterioso permeable: Mecanismos moleculares del cierre y su relación con el tratamiento. Rev Científica Cienc Médica. 2023;26(1):67-76.
3. González MDR, Guzmán EG, Quiles MJP, Tejero MA, Cabañas JMG. Ductus arterioso persistente.
4. Hurtado-Sierra DE. Memorias X Congreso Internacional Médicas UIS 2016 “Cardiología Clínica y Cirugía Cardiovascular”. 2016;
5. González Díaz, CN. Protocolo de Manejo del Ductus Arterioso Persistente en el Neonato [Internet]. 2018 [citado 20 de diciembre de 2024]. Disponible en: https://hn.sld.pa/wp-content/uploads/2022/03/DAP.pdf
6. Guevara DCG, Schvartz DG, Melnik DM, William D, Lugo G, Morejón G. Ductus arterioso: Ecoanatomía y mecanismos de cierre. 2015;
7. Patent Ductus Arteriosus (PDA) [Internet]. [citado 21 de diciembre de 2024]. Disponible en: https://www.stanfordchildrens.org/es/topic/default?id=patent-ductus-arteriosus-pda-90-P04914
8. Medrano C, Zavanella C. Ductus arterioso peristente y ventan aorto pulmonar. 2011 [citado 20 de diciembre de 2024]; Disponible en: https://www.aeped.es/sites/default/files/documentos/7_ductus.pdf
9. Conducto arterioso persistente (CAP) en bebés prematuros: tratamiento y resultados - UpToDate [Internet]. [citado 20 de diciembre de 2024]. Disponible en: https://www.uptodate.com/contents/patent-ductus-arteriosus-pda-in-preterm-infants-management-and-outcome?search=ductus%20arterioso%20persisiten&source=search_result&selectedTitle=1%7E150&usage_type=default&display_rank%20=1
10. Liu Y, Chen S, Zühlke L, Black GC, Choy M kit, Li N, et al. Global birth prevalence of congenital heart defects 1970–2017: updated systematic review and meta-analysis of 260 studies. Int J Epidemiol. 1 de abril de 2019;48(2):455-63.
11. Gálvez-Cuitiva E, Lonngi-Rojas G. Uso del paracetamol para el cierre del conducto arterioso en recién nacidos con edad gestacional menor a 35 semanas. Perinatol Reprod Humana. 1 de diciembre de 2018;32(4):143-50.
12. Declaración PRISMA 2020: una guía actualizada para la publicación de revisiones sistemáticas. Rev Esp Cardiol. 1 de septiembre de 2021;74(9):790-9.
13. Silva HDS da, Franco E de S, Lima LC de AS, Maia MB de S. Therapeutic Efficacy and Safety of Paracetamol versus Ibuprofen in Patent Ductus Arteriosus in Newborns: A Systematic Review. Arq Bras Cardiol. 21 de noviembre de 2024;121(11).
14. Remy A, Vincent M, Pastor-Diez B, Picaud JC. Late postnatal steroid treatment using oral betamethasone can help to close ductus arteriosus in extremely preterm infants who cannot be weaned from ventilation. Eur J Pediatr. 28 de noviembre de 2024;184(1):50.
15. Matsumura S, Masutani S, Oshima A, Kanai M, Namba F, Ishiguro A, et al. Is ibuprofen superior to indomethacin for patent ductus arteriosus in Japanese preterm infants? Pediatr Int. 2021;63(8):929-34.
16. Kimani S, Surak A, Miller M, Bhattacharya S. Use of combination therapy with acetaminophen and ibuprofen for closure of the patent ductus arteriosus in preterm neonates. Paediatr Child Health. 1 de julio de 2021;26(4):e177-83.
17. Early treatment versus expectant management of hemodynamically significant patent ductus arteriosus for preterm infants - Mitra, S - 2020 | Cochrane Library [Internet]. [citado 2 de enero de 2025]. Disponible en: https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD013278.pub2/full
18. Su BH, Lin HY, Chiu HY, Tsai ML, Chen YT, Lu IC. Therapeutic strategy of patent ductus arteriosus in extremely preterm infants. Pediatr Neonatol. 1 de abril de 2020;61(2):133-41.
19. Al-Shaibi S, Abushanab D, Abounahia F, Awaisu A, Al-Badriyeh D. Cost-Effectiveness Analysis of Ibuprofen Versus Indomethacin or Paracetamol for the Treatment of Patent Ductus Arteriosus in Preterm Neonates. Curr Probl Cardiol. 1 de septiembre de 2023;48(9):101751.
20. Dias Maia P, Rodrigues KK, Gien J, Turner MJ. Neonatal acute kidney injury during indomethacin therapy: does it predict ductal closure? J Nephrol. 1 de julio de 2023;36(6):1591-7.
21. Shen X, Huang Y, Guo H, Peng H, Yao S, Zhou M, et al. Oral ibuprofen promoted cholestatic liver disease in very low birth weight infants with patent ductus arteriosus. Clin Res Hepatol Gastroenterol. 1 de marzo de 2021;45(2):101495.
22. Waldvogel S, Atkinson A, Wilbeaux M, Nelle M, Berger MR, Gerull R. High Dose Indomethacin for Patent Ductus Arteriosus Closure Increases Neonatal Morbidity. Am J Perinatol. 30 de diciembre de 2019;38:707-13.
23. de Klerk JCA, van Paassen N, van Beynum IM, Flint RB, Reiss IKM, Simons SHP. Ibuprofen treatment after the first days of life in preterm neonates with patent ductus arteriosus. J Matern Fetal Neonatal Med. 3 de agosto de 2021;34(15):2411-7.
24. Ibuprofen for the treatment of patent ductus arteriosus in preterm or low birth weight (or both) infants - Ohlsson, A - 2020 | Cochrane Library [Internet]. [citado 2 de enero de 2025]. Disponible en: https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD003481.pub8/full
25. Ohlssona A, Shah PS. Paracetamol (acetaminophen) for patent ductus arteriosus in preterm or low birth weight infants - Ohlsson, A - 2020 | Cochrane Library. [citado 2 de enero de 2025]; Disponible en: https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD010061.pub4/full
26. Nishizaki N, Matsuda A, Yoneyama T, Watanabe A, Obinata K, Shimizu T. The influence on renal function of ibuprofen treatment for patent ductus arteriosus in extremely low birthweight infants. Pediatr Int. 2020;62(2):193-9.
27. Chen X, Qiu X, Sun P, Lin Y, Huang Z, Yang C, et al. Neonatal ibuprofen exposure and bronchopulmonary dysplasia in extremely premature infants. J Perinatol. enero de 2020;40(1):124-9.
28. Luo H, He J, Xu X, Chen H, Shi J. The impact of the route of administration on the efficacy and safety of the drug therapy for patent ductus arteriosus in premature infants: a systematic review and meta-analysis. PeerJ. 29 de enero de 2024;12:e16591.
29. Zhong B, Tan K, Razak A, Sackett V, Machipisa C, Zhou L, et al. Early neurodevelopmental outcomes of extreme preterm infants exposed to paracetamol: a retrospective cohort study. Pediatr Res. noviembre de 2023;94(5):1714-9.
30. Seguridad y eficacia comparativas del paracetamol frente a los agentes antiinflamatorios no esteroides en neonatos con conducto arterioso persistente: una revisión sistemática y un metanálisis de ensayos controlados aleatorizados - Katsaras - 2022 - British Journal of Clinical Pharmacology - Wiley Online Library [Internet]. [citado 2 de enero de 2025]. Disponible en: https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bcp.15291
31. Shah SD, Makker K, Nandula P, Smotherman C, Kropf A, Hudak ML. Effectiveness of Dual Medication Therapy (Oral Acetaminophen and Oral Ibuprofen) for the Management of Patent Ductus Arteriosus in Extremely Premature Infants: A Feasibility Trial. Am J Perinatol. 17 de enero de 2021;39:1326-33.
32. Evans P, O’Reilly D, Flyer JN, Soll R, Mitra S. Indomethacin for symptomatic patent ductus arteriosus in preterm infants - Evans, P - 2021 | Cochrane Library. [citado 2 de enero de 2025]; Disponible en: https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD013133.pub2/full
33. López Esparza DE. Búsqueda de variantes genéticas en el gen TFAP2B, en un caso familiar de persistencia del conduto arterioso persistente (PCA) [Internet]. [México]: Universidad Nacional Autónoma de México; 2017 [citado 25 de enero de 2025]. Disponible en: https://ru.dgb.unam.mx/bitstream/20.500.14330/TES01000761730/3/0761730.pdf
34. Beñaldo F. FA, Ferrada D JC, Castillo G. S, Ebensperger D. G, Beñaldo F. FA, Ferrada D JC, et al. Mecanismos regulatorios del tono vascular pulmonar neonatal. Una perspectiva molecular. Rev Chil Enfermedades Respir. diciembre de 2017;33(4):308-15.
35. Silvero Isidre R, Oreggioni Weiberlen M, Mir Ihara P. Relación entre la edad gestacional en recién nacidos con menos de 1500g y ductus arterioso persistente. 2013 [citado 25 de enero de 2025]; Disponible en: http://scielo.iics.una.py/pdf/anales/v45n2/v45n2a04.pdf
36. Ovalı F. Molecular and Mechanical Mechanisms Regulating Ductus Arteriosus Closure in Preterm Infants. Front Pediatr. 2020;8.
37. Schmidt LI, Pozzer Guido A, Sandoval Obregón J, Zárate Lautaro N, Gorodner AM. Explorando la anatomía de los shunts fetales: una descripción detallad. Revista de la Facultad de Medicina de la Universidad Nacional del Nordeste. XLIV(2):20-30.
38. Keb Canul AF. Mecanismo de los AINES y antiinflamatorios derivados para el control del dolor y la inflamación. Uso de antiinflamatorios en odontología. Rev Asoc Dent Mex. 2022;79(1):38-47.
39. Parectamol IV [Internet]. 2020 [citado 25 de enero de 2025]. Disponible en: https://docs.bvsalud.org/biblioref/2024/03/1537531/acetaminofen-endovenoso-ets-2020.pdf
40. Dexametasona 8 mg. Rev Cuba Farm. junio de 2011;45(2):313-7.
41. Silva SC, Molina AB, Seguel MS. Prolonged treatment of patent ductus arteriosus with paracetamol in very low birth weight preterm infants. Andes Pediatr. 2024;95(5):573-82.
42. Potsiurko SO, Dobryanskyy DO, Sekretar LB, Menshykova AO, Salabai ZV, Detsyk OY. MANAGEMENT OF PATENT DUCTUS ARTERIOSUS IN VERY PRETERM NEWBORNS: DO WE HAVE A PREFERENCE? Neonatol Surg Perinat Med. 2019;9(4(34)):51-9.
43. Jasani B, Weisz DE, Reese J, Jain A. Combination pharmacotherapy for patent ductus arteriosus: Rationale and evidence. Semin Perinatol. 1 de marzo de 2023;47(2):151720.
Published
Issue
Section
License
Copyright (c) 2026 MARIO ALBERTO CERQUIN SANGAY, Enzo Renatto Bazualdo Fiorini, Segundo Bueno Ordóñez (Author)
This work is licensed under a Creative Commons Attribution 4.0 International License.
The article is distributed under the Creative Commons Attribution 4.0 License. Unless otherwise stated, associated published material is distributed under the same licence.
