Skip to main content

Thank you for visiting nature.com. 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.

  • Original Article
  • Published:

Prolonged persistent patent ductus arteriosus: potential perdurable anomalies in premature infants

Journal of Perinatology volume 32, pages 953–958 (2012)Cite this article

Subjects

Abstract

Objective:

Patent ductus arteriosus (PDA) is a common condition among preterm infants. Controversy exists regarding the risk-benefit ratio of early closure of PDAs by either medical or surgical treatments. On the other hand, potential morbidities associated with no or delayed closure has not been well studied. The objective of the study was to determine if there is an association of prolonged persistent PDA (PP-PDA) with various morbidities in infants ⩽28 weeks or 1250 g.

Study Design:

This matched case-control analysis includes preterm infants with a diagnosis of PDA over a period of 28 months in a single level III center in the USA. The predictive variable was the presence of a PP-PDA (PDA>3 weeks). Cases were infants with PP-PDA and controls were those with PDA but not PP-PDA (two controls for each case). Outcome variables included days on mechanical ventilation and with oxygen treatment, length of hospital stay, bronchopulmonary dysplasia (BPD), retinopathy of prematurity stage III–V (ROP) necrotizing enterocolitis grade II or more (NEC), delayed growth, direct hyperbilirubinemia >4 mg dl−1 and osteopenia of prematurity. Data was obtained from database collected prospectively and from the review of clinical records when necessary. Statistics included ANOVA, Kaplan–Meier curves and χ2. Significance was set at P<0.05.

Result:

PP-PDA was associated with a significant increase in the number of days of mechanical ventilation, oxygen treatment and length of hospital stay, and in the rates of BPD (60% vs 4.5%), NEC (29% vs 5%), ROP (43% vs 5%), direct hyperbilirubinemia (41% vs 3%), osteopenia (44% vs 6%), parenteral nutrition for >40 days (70% vs 21%), tracheostomy during the hospitalization (15% vs 0%) and delayed growth (70% vs 21%), were also significantly higher in babies with PP-PDA.

Conclusion:

A prolonged exposure to PDA does not seem to be inconsequential for some infants and is associated with an increase prevalence of severe morbidities with potential long lasting effects.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Similar content being viewed by others

Article 16 February 2023

Evdokia Dimitriadis, Daniel L. Rolnik, … Ellen Menkhorst

References

  1. Golombek SG, Sola A, Baquero H, Borbonet D, Cabañas F, Fajardo C et al. First SIBEN Clinical Consensus: diagnostic and therapeutic approach to patent ductus arteriosus in premature newborns. An Pediatr (Barc) 2008; 69 (5): 454–481.

    Article  CAS  Google Scholar 

  2. Sekar KC . Protective strategies to prevent patent ductus arteriosus. Chin Med J (Engl) 2010; 123 (20): 2914–2918.

    Google Scholar 

  3. Schneider DJ, Moore JW . Patent ductus arteriosus. Circulation 2006; 114 (17): 1873–1882.

    Article  PubMed  Google Scholar 

  4. Clyman RI . Mechanisms regulating the ductus arteriosus. Biol Neonate 2006; 89: 330–335.

    Article  PubMed  Google Scholar 

  5. Lee HC, Silverman N, Hintz SR . Diagnosis of patent ductus arteriosus by a neonatologist with a compact, portable ultra-sound machine. J Perinatol 2007; 27 (5): 291–296.

    Article  CAS  PubMed  Google Scholar 

  6. Rojas MA, Gonzalez A, Bancalari E, Claure N, Poole C, Silva-Neto G . Changing trends in the epidemiology and pathogenesis of neonatal chronic lung disease. J Pediatr 1995; 126 (4): 605–610.

    Article  CAS  PubMed  Google Scholar 

  7. Marshall DD, Kotelchuck M, Young TE, Bose CL, Kruyer L, O’Shea TM . Risk factors for chronic lung disease in the surfactant era: a North Carolina population-based study of very low birth weight infants. North Carolina Neonatologists Association. Pediatrics 1999; 104 (6): 1345–1350.

    Article  CAS  PubMed  Google Scholar 

  8. Kluckow M, Evans N . Ductal shunting, high pulmonary blood flow, and pulmonary hemorrhage. J Pediatr 2000; 137: 68–72.

    Article  CAS  PubMed  Google Scholar 

  9. Brown ER . Increased risk of bronchopulmonary dysplasia in infants with patent ductus arteriosus. J Pediatr 1979; 95: 865–866.

    Article  CAS  PubMed  Google Scholar 

  10. Bancalari E, Claure N, Sosenko IR . Bronchopulmonary dysplasia: changes in pathogenesis, epidemiology and definition. Semin Neonatol 2003; 8: 63–71.

    Article  PubMed  Google Scholar 

  11. Hamrick SE, Hansmann G . Patent ductus arteriosus of the preterm infant. Pediatrics 2010; 125 (5): 1020–1030.

    Article  PubMed  Google Scholar 

  12. Ryder RW, Shelton JD, Guinan ME . Necrotizing enterocolitis: a prospective multicenter investigation. Am J Epidemiol 1980; 112 (1): 113–123.

    Article  CAS  PubMed  Google Scholar 

  13. Evans N, Kluckow M . Early ductal shunting and intraventricular haemorrhage in ventilated preterm infants. Arch Dis Child Fetal Neonatal Ed 1996; 75 (3): F183–F186.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Kluckow M, Evans N . Low superior vena cava flow and intraventricular haemorrhage in preterm infants. Arch Dis Child Fetal Neonatal Ed 2000; 82 (3): F188–F194.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Antonucci R, Bassareo P, Zaffanello M, Pusceddu M, Fanos V . Patent ductus arteriosus in the preterm infant: new insights into pathogenesis and clinical management. J Matern Fetal Neonatal Med 2010; 23 (Suppl 3): 34–37.

    Article  PubMed  Google Scholar 

  16. Clyman RI, Chorne N . Patent ductus arteriosus: evidence for and against treatment. J Pediatics 2007; 150: 216–219.

    Article  Google Scholar 

  17. Bell EF, Acarregui MJ . Restricted versus liberal water intake for preventing morbidity and mortality in preterm infants. Cochrane Database System Rev 2008; 1: CD000503.

    Google Scholar 

  18. Mosalli R, Paes B . Patent ductus arteriosus: optimal fluid requirements in preterm infants. Neoreviews 2010; 11: e495–e502.

    Article  Google Scholar 

  19. Stephens BE, Gargus RA, Walden RV, Mance M, Nye J, McKinley L et al. Fluid regimens in the first week of life may increase risk of patent ductus arteriosus in extremely low birth weight infants. J Perinatol 2008; 28: 123–128.

    Article  CAS  PubMed  Google Scholar 

  20. Andriessen P, Struis NC, Niemarkt H, Oetomo SB, Tanke RB, Van Overmeire B . Furosemide in preterm infants treated with indomethacin for patent ductus arteriosus. Acta Paediatr 2009; 98 (5): 797–803.

    Article  CAS  PubMed  Google Scholar 

  21. Toyoshima K, Momma K, Nakanishi T . In vivo dilatation of the ductus arteriosus induced by furosemide in the rat. Pediatr Res 2010; 67 (2): 173–176.

    Article  CAS  PubMed  Google Scholar 

  22. Friedman Z, Demers LM, Marks KH, Uhrrnann S, Maisels MJ . Urinary excretion of prostaglandin E following the administration of furosemide and indomethacin to sick low-birth-weight infants. J Pediatr 1978; 93: 512–515.

    Article  CAS  PubMed  Google Scholar 

  23. Brion LP, Campbell DE . Furosemide in indomethacin-treated infants—systematic review and meta-analysis. Pediatr Nephrol 1999; 13: 212–218.

    Article  CAS  PubMed  Google Scholar 

  24. Thomas RL, Parker GC, Van Overmeire B, Aranda JV . A metaanalysis of ibuprofen versus indomethacin for closure of patent ductus arteriosus. Eur J Pediatr 2005; 164: 135–140.

    Article  CAS  PubMed  Google Scholar 

  25. Jones LJ, Craven PD, Attia J, Thakkinstian A, Wright I . Network meta-analysis of indomethacin versus ibuprofen versus placebo for PDA in preterm infants. Arch Dis Child Fetal Neonatal Ed 2011; 96 (1): F45–F52.

    Article  CAS  PubMed  Google Scholar 

  26. Dollberg S, Lusky A, Reichman B . Patent ductus arteriosus, indomethacin and necrotizing enterocolitis in very low birth weight infants: a population-based study. J Pediatr Gastroenterol Nutr 2005; 40 (2): 184–188.

    Article  CAS  PubMed  Google Scholar 

  27. Attridge JT, Clark R, Walker MW, Gordon PV . New insights into spontaneous intestinal perforation using a national data set: (1) SIP is associated with early indomethacin exposure. J Perinatol 2006; 26 (2): 93–99.

    Article  CAS  PubMed  Google Scholar 

  28. Rao R, Bryowsky K, Mao J, Bunton D, McPherson C, Mathur A . Gastrointestinal complications associated with ibuprofen therapy for patent ductus arteriosus. J Perinatol 2011; 31 (7): 465–470.

    Article  CAS  PubMed  Google Scholar 

  29. Koch J, Hensley G, Roy L, Brown S, Ramaciotti C, Rosenfeld CR . Prevalence of spontaneous closure of the ductus arteriosus in neonates at a birth weight of 1000 grams or less. Pediatrics 2006; 117 (4): 1113–1121.

    Article  PubMed  Google Scholar 

  30. Nemerofsky SL, Parravicini E, Bateman D, Kleinman C, Polin RA, Lorenz JM . The ductus arteriosus rarely requires treatment in infants &gt;1000 grams. Am J Perinatol 2008; 25 (10): 661–666.

    Article  PubMed  Google Scholar 

  31. Herrman K, Bose C, Lewis K, Laughon M . 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): 48–50.

    Article  Google Scholar 

  32. McNamara PJ, Sehgal A . Towards rational management of the patent ductus arteriosus: the need for disease staging. Arch Dis Child Fetal Neonatal Ed 2007; 92: F424–F427.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Bose CL, Laughon M M . Patent ductus arteriosus: lack of evidence for common treatments. Arch Dis Child Fetal Neonatal Ed 2007; 92: F498–F502.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Evans N . Current controversies in the diagnosis and treatment of patent ductus arteriosus in preterm infants. Adv Neonatal Care 2003; 3 (4): 168–177.

    Article  PubMed  Google Scholar 

  35. Jhaveri N, Moon-Grady A, Clyman RI . Early surgical ligation versus a conservative approach for management of patent ductus arteriosus that fails to close after indomethacin treatment. J Pediatr 2010; 157 (3): 381–387, 387.e1.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Ramos FG, Rosenfeld CR, Roy L, Koch J, Ramaciotti C . Echocardiographic predictors of symptomatic patent ductus arteriosus in extremely-low-birth-weight preterm neonates. J Perinatol 2010; 30 (8): 535–539.

    Article  CAS  PubMed  Google Scholar 

  37. Benitz WE . Treatment of persistent patent ductus arteriosus in preterm infants: time to accept the null hypothesis? J Perinatol 2010; 30: 241–252.

    Article  CAS  PubMed  Google Scholar 

  38. Giliberti P, De Leonibus C, Giordano L, Giliberti P . The physiopathology of the patent ductus arteriosus 13. J Matern Fetal Neonatal Med 2009; 22 (Suppl 3): 6–9.

    Article  PubMed  Google Scholar 

  39. 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.

    Article  PubMed  Google Scholar 

  40. Fowlie PW, Davis PG, McGuire W . Prophylactic intravenous indomethacin for preventing mortality and morbidity in preterm infants. Cochrane Database Syst Rev 2010; 7: CD000174.

    Google Scholar 

  41. Lin YC, Huang HR, Lien R, Yang PH, Su WJ, Chung HT . et al. Management of patent ductus arteriosus in term or near-term neonates with respiratory distress. Pediatr Neonatol 2010; 51 (3): 160–165.

    Article  PubMed  Google Scholar 

  42. Noori S, McCoy M, Friedlich P, Bright B, Gottipati V, Seri I et al. Failure of ductus arteriosus closure is associated with increased mortality in preterm infants. Pediatrics 2009; 123 (1): e138–e144).

    Article  PubMed  Google Scholar 

  43. Brooks JM, Travadi JN, Patole SK, Doherty DA, Simmer K . Is surgical ligation of patent ductus arteriosus necessary? The Western Australian experience of conservative management. Arch Dis Child Fetal Neonatal Ed 2005; 90 (3): F235–F239.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Saldeno YP, Favareto V, Rogido M, Sola A . Late onset neonatal pulmonary hypertension: role of persistently prolonged patent ductus? PAS-SPR, Abstract, May 2008.

  45. Oh W, Poindexter BB, Perritt R, Lemons JA, Bauer CR, Ehrenkranz RA, et al., Neonatal Research Network. Association between fluid intake and weight loss during the first ten days of life and risk of bronchopulmonary dysplasia in extremely low birth weight infants. J Pediatr 2005; 147 (6): 786–790.

    Article  PubMed  Google Scholar 

  46. Brion LP, Campbell DE . Furosemide for symptomatic patent ductus arteriosus in indomethacin-treated infants. Cochrane Database Syst Rev 2001; 3: CD001148.

    Google Scholar 

  47. Heymann MA, Rudolph AM, Silverman NH . Closure of the ductus arteriosus in premature infants by inhibition of prostaglandin systesis. N Engl J Med 1976; 295: 530.

    Article  CAS  PubMed  Google Scholar 

  48. Friedman WE, Hirschklau MJ, Printz MP, Pltlick PT, Kirkpatrick SE . Pharmacologic closure of patent ductus arteriosus in the premature infant. N Engl J Med 1976; 295: 526.

    Article  CAS  PubMed  Google Scholar 

  49. Noori S . ductus arteriosus in the preterm infant: to treat or not to treat? J Perinatol 2010; 30 (Suppl): S31–S37.

    Article  PubMed  Google Scholar 

  50. Knight DB, Laughon MM . Evidence for active closure of patent ductus arteriosus in very preterm infants. J Pediatr 2008; 152 (3): 446–447; author reply 447–8.

    Article  PubMed  Google Scholar 

  51. Bose CL, Laughon M . Treatment to prevent patency of the ductus arteriosus: beneficial or harmful? J Pediatr 2006; 148 (6): 713–714.

    Article  PubMed  Google Scholar 

  52. Laughon M, Bose C, Benitz WE . ductus arteriosus management: what are the next steps? J Pediatr 2010; 157 (3): 355–357.

    Article  PubMed  Google Scholar 

  53. Farstad T, Bratlid D, Medbø S, Markestad T, Norwegian Extreme Prematurity Study Group. Bronchopulmonary dysplasia - prevalence, severity and predictive factors in a national cohort of extremely premature infants. Acta Paediatr 2011; 100 (1): 53–58.

    Article  CAS  PubMed  Google Scholar 

  54. Silverman WA . Where's the evidence? The Western Australian experience of conservative management. Oxford University Press: Oxford, United Kingdom, 1999.

    Book  Google Scholar 

  55. Richardson DK, Gray JE, McCormick MC, Workman K, Goldmann DA . Score for Neonatal Acute Physiology: a physiologic severity index for neonatal intensive care. Pediatrics 1993; 91 (3): 617–623.

    CAS  PubMed  Google Scholar 

  56. Richardson DK, Phibbs CS, Gray JE, McCormick MC, Workman-Daniels K, Goldmann DA . Birth weight and illness severity: independent predictors of neonatal mortality. Pediatrics 1993; 91 (5): 969–975.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We are thankful to Dr Augusto Sola for his guidance and support in developing the hypothesis and the study design, and for helping us in writing this manuscript.

Author information

Authors and Affiliations

  1. Division of Neonatal-Perinatal Medicine, BC Children's Hospital, Vancouver, BC, Canada

    Y P Saldeño

  2. Division of Neonatal-Perinatal Medicine, Rosario Hospital, Rosario, Argentina

    V Favareto

  3. Division of Neonatal-Perinatal Medicine, University of Texas Southwestern, Dallas, TX, USA

    J Mirpuri

Authors
  1. Y P Saldeño
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. V Favareto
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J Mirpuri
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Y P Saldeño.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Saldeño, Y., Favareto, V. & Mirpuri, J. Prolonged persistent patent ductus arteriosus: potential perdurable anomalies in premature infants. J Perinatol 32, 953–958 (2012). https://doi.org/10.1038/jp.2012.31

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/jp.2012.31

Keywords

This article is cited by

Search

Advanced search

Quick links