Newborn

Register      Login

SEARCH WITHIN CONTENT

FIND ARTICLE

Volume / Issue

Online First

Related articles

VOLUME 1 , ISSUE 1 ( January-March, 2022 ) > List of Articles

REVIEW ARTICLE

Patent Ductus Arteriosus: A Diagnostic and Treatment Dilemma

Rachana Singh, Ruben Vaidya, Ravi Ashwath, Akhil Maheshwari

Keywords : Ductus arteriosus, Neonate, Patent ductus arteriosus, Prematurity

Citation Information : Singh R, Vaidya R, Ashwath R, Maheshwari A. Patent Ductus Arteriosus: A Diagnostic and Treatment Dilemma. 2022; 1 (1):58-66.

DOI: 10.5005/jp-journals-11002-0023

License: CC BY-NC 4.0

Published Online: 31-03-2022

Copyright Statement:  Copyright © 2022; The Author(s).


Abstract

Ductus arteriosus is a critically important vascular structure that functions as an extracardiac shunt in fetal life between the pulmonary and systemic circulations for optimal utilization of the placenta as a gas exchange organ and fetal well-being. While morbidities and mortality are well known to be associated with persistence of patent ductus arteriosus (PDA) in postnatal life, the treatment options have concerns for adverse outcomes. Additionally, high spontaneous closure rates, lack of clear definition of hemodynamically significant PDA (hs-PDA), ideal diagnostic tools, conflicting evidence regarding timing of treatment, and lack of clear benefits of PDA treatment from randomized trial in reducing adverse outcomes continue to pose challenges for clinicians managing preterm infants with PDA. This review focuses on the pathophysiology, current diagnostic and management practices, as well as the potential of utilizing unique diagnostic tools to support precision medicine for preterm infants with hs-PDA.


HTML PDF Share
  1. Raju TNK. From Galen to Gross and beyond: a brief history of the enigmatic patent ductus arteriosus. J Perinatol 2019;39(11):1442–1448. DOI: 10.1038/s41372-019-0517-4.
  2. Enzensberger C, Wienhard J, Weichert J, et al. Idiopathic constriction of the fetal ductus arteriosus: three cases and review of the literature. J Ultrasound Med 2012;31(8):1285–1291. DOI: 10.7863/jum.2012.31.8.1285.
  3. Operle M, Anderson S. Premature closure of the ductus arteriosus in an otherwise healthy fetus. J Diagn Med Sonogr 2019;35(3):235–239. DOI: 10.1177/8756479318824315.
  4. Schneider DJ, Moore JW. Patent ductus arteriosus. Circulation 2006;114(17):1873–1882. DOI: 10.1161/CIRCULATIONAHA.105.592063.
  5. Schena F, Francescato G, Cappelleri A, et al. Association between hemodynamically significant patent ductus arteriosus and bronchopulmonary dysplasia. J Pediatr 2015;166(6):1488–1492. DOI: 10.1016/j.jpeds.2015.03.012.
  6. Abu-Shaweesh JM, Almidani E. PDA: does it matter? Int J Pediatr Adolesc Med 2020;7(1):9–12. DOI: 10.1016/j.ijpam.2019.12.001.
  7. El Hajjar M, Vaksmann G, Rakza T, et al. Severity of the ductal shunt: a comparison of different markers. Arch Dis Child Fetal Neonatal Ed 2005;90(5):F419–F422. DOI: 10.1136/adc.2003.027698.
  8. Clyman RI. Patent ductus arteriosus, its treatments, and the risks of pulmonary morbidity. Semin Perinatol 2018;42(4):235–242. DOI: 10.1053/j.semperi.2018.05.006.
  9. Semberova J, Sirc J, Miletin J, et al. Spontaneous closure of patent ductus arteriosus in infants ≤1500 g. Pediatrics 2017;140(2):e20164258. DOI: 10.1542/peds.2016-4258.
  10. Sung SI, Chang YS, Ahn SY, et al. Conservative non-intervention approach for hemodynamically significant patent ductus arteriosus in extremely preterm infants. Front Pediatr 2020;8:605134. DOI: 10.3389/fped.2020.605134.
  11. Slaughter JL, Reagan PB, Newman TB, et al. Comparative effectiveness of nonsteroidal anti-inflammatory drug treatment vs no treatment for patent ductus arteriosus in preterm infants. JAMA Pediatr 2017;171(3):e164354. DOI: 10.1001/jamapediatrics.2016.4354.
  12. Clyman RI, Liebowitz M, Kaempf J, 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.e6. DOI: 10.1016/j.jpeds.2018.09.012.
  13. Willis KA, Weems MF. Hemodynamically significant patent ductus arteriosus and the development of bronchopulmonary dysplasia. Congenit Heart Dis 2019;14(1):27–32. DOI: 10.1111/chd.12691.
  14. Lakshminrusimha S, Saugstad OD. The fetal circulation, pathophysiology of hypoxemic respiratory failure and pulmonary hypertension in neonates, and the role of oxygen therapy. J Perinatol 2016;36(Suppl 2):S3–S11. DOI: 10.1038/jp.2016.43.
  15. Smith GC. The pharmacology of the ductus arteriosus. Pharmacol Rev 1998;50(1):35–58. PMID: 9549757.
  16. Ivey KN, Srivastava D. The paradoxical patent ductus arteriosus. J Clin Invest 2006;116(11):2863–2865. DOI: 10.1172/JCI30349.
  17. Fan FL, Zhu S, Chen LH, et al. Role of prostaglandin E and its receptors in the process of ductus arteriosus maturation and functional closure in the rabbit. Clin Exp Pharmacol Physiol 2010;37(5–6):574–580. DOI: 10.1111/j.1440-1681.2010.05354.x.
  18. Dice JE, Bhatia J. Patent ductus arteriosus: an overview. J Pediatr Pharmacol Ther 2007;12(3):138–146. DOI: 10.5863/1551-6776- 12.3.138.
  19. de Klerk JCA, Engbers AGJ, van Beek F, et al. Spontaneous closure of the ductus arteriosus in preterm infants: a systematic review. Front Pediatr 2020;8:541. DOI: 10.3389/fped.2020.00541.
  20. Romagnoli V, Pedini A, Santoni M, et al. Patent ductus arteriosus in preterm infants born before 30 weeks’ gestation: high rate of spontaneous closure after hospital discharge. Cardiol Young 2018;28(8):995–1000. DOI: 10.1017/S1047951118000641.
  21. Liu C, Zhu X, Li D, et al. Related factors of patent ductus arteriosus in preterm infants: a systematic review and meta-analysis. Front Pediatr 2020;8:605879. DOI: 10.3389/fped.2020.605879.
  22. Gillam-Krakauer M, Reese J. Diagnosis and management of patent ductus arteriosus. Neoreviews 2018;19(7):e394–e402. DOI: 10.1542/neo.19-7-e394.
  23. Smith A, El-Khuffash AF. Defining “Haemodynamic significance” of the patent ductus arteriosus: do we have all the answers? Neonatology 2020;117(2):225–232. DOI: 10.1159/000506988.
  24. Zonnenberg I, de Waal K. The definition of a haemodynamic significant duct in randomized controlled trials: a systematic literature review. Acta Paediatr 2012;101(3):247–251. DOI: 10.1111/j.1651-2227.2011.02468.x.
  25. Shepherd JL, Noori S. What is a hemodynamically significant PDA in preterm infants? Congenit Heart Dis 2019;14(1):21–26. DOI: 10.1111/chd.12727.
  26. Kluckow M, Lemmers P. Hemodynamic assessment of the patent ductus arteriosus: beyond ultrasound. Semin Fetal Neonatal Med 2018;23(4):239–244. DOI: 10.1016/j.siny.2018.04.002.
  27. Kindler A, Seipolt B, Heilmann A, et al. Development of a diagnostic clinical score for hemodynamically significant patent ductus arteriosus. Front Pediatr 2017;5:280. DOI: 10.3389/fped.2017.00280.
  28. Gonen I, Babayigit A, Bornaun H, et al. SIMPLE: a novel scoring system for predicting hemodynamically significant patent ductus arteriosus without echocardiographic evaluation in extremely low birth weight infants. Front Pediatr 2021;9:649515. DOI: 10.3389/fped.2021.649515.
  29. El-Khuffash A, James AT, Corcoran JD, et al. A patent ductus arteriosus severity score predicts chronic lung disease or death before discharge. J Pediatr 2015;167(6):1354–1361.e2. DOI: 10.1016/j.jpeds.2015.09.028.
  30. Montaner A, Pinillos R, Galve Z, et al. Brain natriuretic propeptide as an early marker of bronchopulmonary dysplasia or death in the preterm newborn. Klin Padiatr 2017;229(4):223–228. DOI: 10.1055/s-0043-111597.
  31. Dasgupta S, Aly AM, Malloy MH, et al. NTproBNP as a surrogate biomarker for early screening of pulmonary hypertension in preterm infants with bronchopulmonary dysplasia. J Perinatol 2018;38(9):1252–1257. DOI: 10.1038/s41372-018-0164-1.
  32. Sellmer A, Hjortdal VE, Bjerre JV, et al. Cardiovascular biomarkers in the evaluation of patent ductus arteriosus in very preterm neonates: a cohort study. Early Hum Dev 2020;149:105142. DOI: 10.1016/j.earlhumdev.2020.105142.
  33. Iliodromiti Z, Christou E, Vrachnis N, et al. Serum and urinary N-terminal pro-brain natriuretic peptides as biomarkers for bronchopulmonary dysplasia of preterm neonates. Front Pediatr 2020;8:588738. DOI: 10.3389/fped.2020.588738.
  34. Olsson KW, Larsson A, Jonzon A, et al. Exploration of potential biochemical markers for persistence of patent ductus arteriosus in preterm infants at 22-27 weeks’ gestation. Pediatr Res 2019;86(3):333–338. DOI: 10.1038/s41390-018-0182-x.
  35. Singh Y, Fraisse A, Erdeve O, et al. Echocardiographic diagnosis and hemodynamic evaluation of patent ductus arteriosus in extremely low gestational age newborn (ELGAN) infants. Front Pediatr 2020;8:573627. DOI: 10.3389/fped.2020.573627.
  36. Broadhouse KM, Price AN, Durighel G, et al. Assessment of PDA shunt and systemic blood flow in newborns using cardiac MRI. NMR Biomed 2013;26(9):1135–1141. DOI: 10.1002/nbm.2927.
  37. de Freitas Martins F, Ibarra Rios D, MH FR, et al. Relationship of patent ductus arteriosus size to echocardiographic markers of shunt volume. J Pediatr 2018;202:50–55.e3. DOI: 10.1016/j.jpeds.2018.06.045.
  38. van Laere D, van Overmeire B, Gupta S, et al. Application of NPE in the assessment of a patent ductus arteriosus. Pediatr Res 2018;84 (Suppl 1):46–56. DOI: 10.1038/s41390-018-0077-x.
  39. Roushdy A, Fiky AE, Din DE. Visualization of patent ductus arteriosus using real-time three-dimensional echocardiogram: comparative study with 2D echocardiogram and angiography. J Saudi Heart Assoc 2012;24(3):177–186. DOI: 10.1016/j.jsha.2012.02.001.
  40. Cavalcante JL, Lalude OO, Schoenhagen P, et al. Cardiovascular magnetic resonance imaging for structural and valvular heart disease interventions. JACC Cardiovasc Interv 2016;9(5):399–425. DOI: 10.1016/j.jcin.2015.11.031.
  41. Marín Rodríguez C, Sánchez Alegre ML, Lancharro Zapata Á, et al. What radiologists need to know about the pulmonary-systemic flow ratio (Qp/Qs): what it is, how to calculate it, and what it is for. Radiologia 2015;57(5):369–379. DOI: 10.1016/j.rx.2015.04.001.
  42. Chock VY, Rose LA, Mante JV, et al. Near-infrared spectroscopy for detection of a significant patent ductus arteriosus. Pediatr Res 2016;80(5):675–680. DOI: 10.1038/pr.2016.148.
  43. Lemmers PM, Toet MC, van Bel F. Impact of patent ductus arteriosus and subsequent therapy with indomethacin on cerebral oxygenation in preterm infants. Pediatrics 2008;121(1):142–147. DOI: 10.1542/peds.2007-0925.
  44. van der Laan ME, Roofthooft MT, Fries MW, et al. A hemodynamically significant patent ductus arteriosus does not affect cerebral or renal tissue oxygenation in preterm infants. Neonatology 2016;110(2):141–147. DOI: 10.1159/000445101.
  45. Sankar MN, Bhombal S, Benitz WE. PDA: to treat or not to treat. Congenit Heart Dis 2019;14(1):46–51. DOI: 10.1111/chd.12708.
  46. Benitz WE. Patent ductus arteriosus: to treat or not to treat? Arch Dis Child Fetal Neonatal Ed 2012;97(2):F80–F82. DOI: 10.1136/archdischild-2011-300381.
  47. Singh R, Gorstein SV, Bednarek F, et al. A predictive model for SIVH risk in preterm infants and targeted indomethacin therapy for prevention. Sci Rep 2013;3:2539. DOI: 10.1038/srep02539.
  48. Reese J, Shelton EL, Slaughter JC, et al. Prophylactic Indomethacin Revisited. J Pediatr 2017;186:11–14.e1. DOI: 10.1016/j.jpeds.2017.03.036.
  49. Benitz WE. Treatment of persistent patent ductus arteriosus in preterm infants: time to accept the null hypothesis? J Perinatol 2010;30(4):241–252. DOI: 10.1038/jp.2010.3.
  50. Lee JA. Practice for preterm patent ductus arteriosus; focusing on the hemodynamic significance and the impact on the neonatal outcomes. Korean J Pediatr 2019;62(7):245–251. DOI: 10.3345/kjp.2018.07213.
  51. Ohlsson A, Shah PS. Paracetamol (acetaminophen) for patent ductus arteriosus in preterm or low birth weight infants. Cochrane Database Syst Rev 2020;1(1):Cd010061. DOI: 10.1002/14651858.CD010061.pub4.
  52. Oncel MY, Yurttutan S, Erdeve O, 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):510–514.e1. DOI: 10.1016/j.jpeds.2013.11.008.
  53. Al-Lawama M, Alammori I, Abdelghani T, et al. Oral paracetamol versus oral ibuprofen for treatment of patent ductus arteriosus. J Int Med Res 2018;46(2):811–818. DOI: 10.1177/0300060517722698.
  54. Ohlsson A, Shah SS. Ibuprofen for the prevention of patent ductus arteriosus in preterm and/or low birth weight infants. Cochrane Database Syst Rev 2011;(7):CD004213. DOI: 10.1002/14651858.CD004213.pub3.
  55. Chiruvolu A, Jaleel MA. Pathophysiology of patent ductus arteriosus in premature neonates. Early Hum Dev 2009;85(3):143–146. DOI: 10.1016/j.earlhumdev.2008.12.006.
  56. Zecca E, Romagnoli C, De Carolis MP, et al. Does Ibuprofen increase neonatal hyperbilirubinemia? Pediatrics 2009;124(2):480–484. DOI: 10.1542/peds.2008-2433.
  57. Erdeve O, Sarici SU, Sari E, et al. Oral-ibuprofen-induced acute renal failure in a preterm infant. Pediatr Nephrol 2008;23(9):1565–1567. DOI: 10.1007/s00467-008-0835-9.
  58. Huang X, Wang F, Wang K. Paracetamol versus ibuprofen for the treatment of patent ductus arteriosus in preterm neonates: a meta-analysis of randomized controlled trials. J Matern Fetal Neonatal Med 2018;31(16):2216–2222. DOI: 10.1080/14767058.2017.1338263.
  59. Vaidya R, Wilson D, Paris Y, et al. Use of acetaminophen for patent ductus arteriosus treatment: a single center experience. J Matern Fetal Neonatal Med 2020;33(16):2723–2729. DOI: 10.1080/14767058.2018.1559810.
  60. Vaidya R, Knee A, Paris Y, et al. Predictors of successful patent ductus arteriosus closure with acetaminophen in preterm infants. J Perinatol 2021;41(5):998–1006. DOI: 10.1038/s41372-020-00803-y.
  61. Fowlie PW, Davis PG, McGuire W. Prophylactic intravenous indomethacin for preventing mortality and morbidity in preterm infants. Cochrane Database Syst Rev 2010;2010(7):CD000174. DOI: 10.1002/14651858.CD000174.pub2.
  62. Ment LR, Oh W, Ehrenkranz RA, et al. Low-dose indomethacin therapy and extension of intraventricular hemorrhage: a multicenter randomized trial. J Pediatr 1994;124(6):951–955. DOI: 10.1016/s0022-3476(05)83191-9.
  63. Mirza H, Oh W, Laptook A, et al. Indomethacin prophylaxis to prevent intraventricular hemorrhage: association between incidence and timing of drug administration. J Pediatr 2013;163(3):706–710.e1. DOI: 10.1016/j.jpeds.2013.02.030.
  64. Aranda JV, Clyman R, Cox B, et al. A randomized, double-blind, placebo-controlled trial on intravenous ibuprofen L-lysine for the early closure of nonsymptomatic patent ductus arteriosus within 72 hours of birth in extremely low-birth-weight infants. Am J Perinatol 2009;26(3):235–245. DOI: 10.1055/s-0028-1103515.
  65. Amoozgar H, Ghodstehrani M, Pishva N. Oral ibuprofen and ductus arteriosus closure in full-term neonates: a prospective case-control study. Pediatr Cardiol 2010;31(1):40–43. DOI: 10.1007/s00246-009-9542-y.
  66. Ohlsson A, Shah PS. Paracetamol (acetaminophen) for patent ductus arteriosus in preterm or low-birth-weight infants. Cochrane Database Syst Rev 2015(3):CD010061. DOI: 10.1002/14651858.CD010061.pub3.
  67. Mitra S, Florez ID, Tamayo ME, 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. Journal of the American Medical Association 2018;319(12):1221–1238. DOI: 10.1001/jama.2018.1896.
  68. Koehne PS, Bein G, Alexi-Meskhishvili V, et al. Patent ductus arteriosus in very low birthweight infants: complications of pharmacological and surgical treatment. J Perinat Med 2001;29(4):327–334. DOI: 10.1515/JPM.2001.047.
  69. Zbar RI, Chen AH, Behrendt DM, et al. Incidence of vocal fold paralysis in infants undergoing ligation of patent ductus arteriosus. Ann Thorac Surg 1996;61(3):814–816. DOI: 10.1016/0003-4975(95)01152-8.
  70. Chorne N, Leonard C, Piecuch R, et al. Patent ductus arteriosus and its treatment as risk factors for neonatal and neurodevelopmental morbidity. Pediatrics 2007;119(6):1165–1174. DOI: 10.1542/peds.2006-3124.
  71. Kabra NS, Schmidt B, Roberts RS, et al. Neurosensory impairment after surgical closure of patent ductus arteriosus in extremely low birth weight infants: results from the Trial of Indomethacin Prophylaxis in Preterms. J Pediatr 2007;150(3):229–234, 234.e1. DOI: 10.1016/j.jpeds.2006.11.039.
  72. Hagadorn JI, Brownell EA, Trzaski JM, et al. Trends and variation in management and outcomes of very low-birth-weight infants with patent ductus arteriosus. Pediatr Res 2016;80(6):785–792. DOI: 10.1038/pr.2016.166.
  73. Othman HF, Linfield DT, Mohamed MA, et al. Ligation of patent ductus arteriosus in very low birth weight premature infants. Pediatr Neonatol 2020;61(4):399–405. DOI: 10.1016/j.pedneo.2020.03.009.
  74. Ngo ST, Profit J, Gould JB, et al. Changing trends in the management of patent ductus arteriosus for very low birth weight infants. Pediatrics 2018;141(1 Meeting Abstract):507. DOI: 10.1542/peds.141.1MA6.507.
  75. Lee LC, Tillett A, Tulloh R, et al. Outcome following patent ductus arteriosus ligation in premature infants: a retrospective cohort analysis. BMC Pediatr 2006;6(1):15. DOI: 10.1186/1471- 2431-6-15.
  76. Backes CH, Rivera BK, Bridge JA, et al. Percutaneous Patent Ductus Arteriosus (PDA) closure during infancy: a meta-analysis. Pediatrics 2017;139(2):e20162927. DOI: 10.1542/peds.2016-2927.
  77. Sathanandam SK, Gutfinger D, O'Brien L, et al. Amplatzer Piccolo Occluder clinical trial for percutaneous closure of the patent ductus arteriosus in patients ≥700 grams. Catheter Cardiovasc Interv 2020;96(6):1266–1276. DOI: 10.1002/ccd.28973.
  78. Regan W, Benbrik N, Sharma SR, et al. Improved ventilation in premature babies after transcatheter versus surgical closure of patent ductus arteriosus. Int J Cardiol 2020;311:22–27. DOI: 10.1016/j.ijcard.2020.03.040.
  79. Fraisse A, Bautista-Rodriguez C, Burmester M, et al. Transcatheter closure of patent ductus arteriosus in infants with weight under 1,500 grams. Front Pediatr 2020;8:558256. DOI: 10.3389/fped.2020.558256.
  80. Parkerson S, Philip R, Talati A, et al. Management of patent ductus arteriosus in premature infants in 2020. Front Pediatr 2020;8:590578. DOI: 10.3389/fped.2020.590578.
  81. Serrano RM, Madison M, Lorant D, et al. Comparison of ‘post-patent ductus arteriosus ligation syndrome’ in premature infants after surgical ligation vs percutaneous closure. J Perinatol 2020;40(2): 324–329. DOI: 10.1038/s41372-019-0513-8.
  82. Ulrich TJB, Hansen TP, Reid KJ, et al. Post-ligation cardiac syndrome is associated with increased morbidity in preterm infants. J Perinatol 2018;38(5):537–542. DOI: 10.1038/s41372-018-0056-4.
  83. Philip R, Waller B, Chilakala S, et al. Comparison of low cardiac output syndrome after PDA ligation and transcatheter PDA closure in extremely low birth weight infants. J Am Coll Cardiol 2019:575. DOI: 10.1016/S0735-1097(19)31183-0.
PDF Share
PDF Share

© Jaypee Brothers Medical Publishers (P) LTD.