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.

Patent ductus arteriosus in premature infants: to treat or not to treat?

Abstract

Objective:

Closing patent ductus arteriosus (PDA) is a widely accepted approach in the management of very low birth weight (VLBW) infants. Our objective is to test the hypothesis that conservative management (no treatment) of PDA will not affect survival without chronic lung diseases (CLD).

Study Design:

This retrospective study utilizes a prospectively collected database to compare two cohorts of VLBW infants. Infants in the first group (2001 to 2009) had their PDA treated with pharmacological and if necessary with surgical ligation. PDA in the second group (2010 to 2014) was not treated with medical or surgical intervention. The primary outcome was survival without oxygen requirement at 36 weeks. Pulmonary and non-pulmonary morbidities were also compared. Logistic regression analyses were performed to control for confounders.

Results:

This study included 643 VLBW infants, of them 415 infants in the Treat group and 228 in the No-Treat group. The rate of survival without CLD did not differ between Treat and No-Treat groups (78.4% vs 83.9%, respectively; adjusted odds ratio (aOR)=1.72, confidence interval (CI): 0.92 to 3.23, P=0.09). Mortality declined in No-Treat group (15.2% vs 10.5%, aOR=0.51, CI: 0.25 to 0.99, P=0.049), but the two groups did not differ in the incidence of CLD among survivors (5.8% vs 5.0%,=P0.47). Pulmonary complications and non-pulmonary morbidities did not differ between groups.

Conclusions:

Conservative management (no treatment) of PDA may not compromise survival without CLD and is not associated with increased morbidities in VLBW infants. Prospective physiological studies are needed to determine the sector of VLBW infants, if any, who could benefit from PDA treatment.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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

Figure 1
Figure 2

References

  1. Kitterman JA . Patent ductus arteriosus: current clinical status. Arch Dis Child 1980; 55 (2): 106–109.

    Article  CAS  Google Scholar 

  2. Kitterman JA, Edmunds LH Jr, Gregory GA, Heymann MA, Tooley WH, Rudolph AM . Patent ducts arteriosus in premature infants. Incidence, relation to pulmonary disease and management. N Engl J Med 1972; 287 (10): 473–477.

    Article  CAS  Google Scholar 

  3. Kluckow M, Evans N . Ductal shunting, high pulmonary blood flow, and pulmonary hemorrhage. J Pediatr 2000; 137 (1): 68–72.

    Article  CAS  Google Scholar 

  4. 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  Google Scholar 

  5. 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  Google Scholar 

  6. Laughon MM, Simmons MA, Bose CL . Patency of the ductus arteriosus in the premature infant: is it pathologic? Should it be treated? Curr Opin Pediatr 2004; 16 (2): 146–151.

    Article  Google Scholar 

  7. Morrow WR, Taylor AF, Kinsella JP, Lally KP, Gerstmann DR, deLemos RA . Effect of ductal patency on organ blood flow and pulmonary function in the preterm baboon with hyaline membrane disease. Crit Care Med 1995; 23 (1): 179–186.

    Article  CAS  Google Scholar 

  8. Meyers RL, Alpan G, Lin E, Clyman RI . Patent ductus arteriosus, indomethacin, and intestinal distension: effects on intestinal blood flow and oxygen consumption. Pediatr Res 1991; 29 (6): 569–574.

    Article  CAS  Google Scholar 

  9. Benitz WE . Treatment of persistent patent ductus arteriosus in preterm infants: time to accept the null hypothesis. J Perinatol 2010; 30 (4): 241–252.

    Article  CAS  Google Scholar 

  10. Peckham GJ, Miettinen OS, Ellison RC, Kraybill EN, Gersony WM, Zierler S et al. Clinical course to 1 year of age in premature infants with patent ductus arteriosus: results of a multicenter randomized trial of indomethacin. J Pediatr 1984; 105 (2): 285–291.

    Article  CAS  Google Scholar 

  11. Schmidt B, Roberts RS, Fanaroff A, Davis P, Kirpalani HM, Nwaesei C et al. Indomethacin prophylaxis, patent ductus arteriosus, and the risk of bronchopulmonary dysplasia: further analyses from the Trial of Indomethacin Prophylaxis in Preterms (TIPP). J Pediatr 2006; 148: 6.

    Article  Google Scholar 

  12. Fanos V, Benini D, Verlato G, Errico G, Cuzzolin L . Efficacy and renal tolerability of ibuprofen vs. indomethacin in preterm infants with patent ductus arteriosus. Fundam Clin Pharmacol 2005; 19 (2): 187–193.

    Article  CAS  Google Scholar 

  13. Shorter NA, Liu JY, Mooney DP, Harmon BJ . Indomethacin-associated bowel perforations: a study of possible risk factors. J Pediatr Surg 1999; 34 (3): 442–444.

    Article  CAS  Google Scholar 

  14. Watterberg KL, Gerdes JS, Cole CH, Aucott SW, Thilo EH, Mammel MC et al. Prophylaxis of early adrenal insufficiency to prevent bronchopulmonary dysplasia: a multicenter trial. Pediatrics 2004; 114 (6): 1649–1657.

    Article  Google Scholar 

  15. Van Bel F, Van de Bor M, Stijnen T, Baan J, Ruys JH . Cerebral blood flow velocity changes in preterm infants after a single dose of indomethacin: duration of its effect. Pediatrics 1989; 84 (5): 802–807.

    CAS  PubMed  Google Scholar 

  16. Ohlsson A, Walia R, Shah SS . Ibuprofen for the treatment of patent ductus arteriosus in preterm or low birth weight (or both) infants. Cochrane Database Syst Rev 2015; 2: Cd003481.

    Google Scholar 

  17. Sekar KC, Corff KE . Treatment of patent ductus arteriosus: indomethacin or ibuprofen? J Perinatol 2008; 28 (Suppl 1): S60–S62.

    Article  CAS  Google Scholar 

  18. Ohlsson A, Shah PS . Paracetamol (acetaminophen) for patent ductus arteriosus in preterm or low-birth-weight infants. Cochrane Database Syst Rev 2015; 3: Cd010061.

    Google Scholar 

  19. Chorne N, Leonard C, Piecuch R, Clyman RI . Patent ductus arteriosus and its treatment as risk factors for neonatal and neurodevelopmental morbidity. Pediatrics 2007; 119 (6): 1165–1174.

    Article  Google Scholar 

  20. The Victorian Infant Collaborative Study Group. Surgery and the tiny baby: sensorineural outcome at 5 years of age. J Paediatr Child Health 1996; 32 (2):167–172.

  21. Kabra NS, Schmidt B, Roberts RS, Doyle LW, Papile L, Fanaroff A . 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.

    Article  CAS  Google Scholar 

  22. Wickremasinghe AC, Rogers EE, Piecuch RE, Johnson BC, Golden S, Moon-Grady AJ et al. Neurodevelopmental outcomes following two different treatment approaches (early ligation and selective ligation) for patent ductus arteriosus. J Pediatr 2012; 161 (6): 1065–1072.

    Article  Google Scholar 

  23. Clement WA, El-Hakim H, Phillipos EZ, Coté JJ . Unilateral vocal cord paralysis following patent ductus arteriosus ligation in extremely low-birth-weight infants. Arch Otolaryngol Head Neck Surg 2008; 134 (1): 28–33.

    Article  Google Scholar 

  24. Smith ME, King JD, Elsherif A, Muntz HR, Park AH, Kouretas PC . Should all newborns who undergo patent ductus arteriosus ligation be examined for vocal fold mobility? Laryngoscope 2009; 119 (8): 1606–1609.

    Article  Google Scholar 

  25. Mandhan P, Brown S, Kukkady A, Samarakkody U . Surgical closure of patent ductus arteriosus in preterm low birth weight infants. Congenit Heart Dis 2009; 4 (1): 34–37.

    Article  Google Scholar 

  26. Lippmann M, Nelson RJ, Emmanouilides GC, Diskin J, Thibeault DW . Ligation of patent ductus arteriosus in premature infants. Br J Anaesth 1976; 48 (4): 365–369.

    Article  CAS  Google Scholar 

  27. Gould DS, Montenegro LM, Gaynor JW, Lacy SP, Ittenbach R, Stephens P et al. A comparison of on-site and off-site patent ductus arteriosus ligation in premature infants. Pediatrics 2003; 112 (6 I): 1298–1301.

    Article  Google Scholar 

  28. Roclawski M, Sabiniewicz R, Potaz P, Smoczynski A, Pankowski R, Mazurek T et al. Scoliosis in patients with aortic coarctation and patent ductus arteriosus: does standard posterolateral thoracotomy play a role in the development of the lateral curve of the spine? Pediatr Cardiol 2009; 30 (7): 941–945.

    Article  Google Scholar 

  29. Shelton JE, Julian R, Walburgh E, Schneider E . Functional scoliosis as a long-term complication of surgical ligation for patent ductus arteriosus in premature infants. J Pediatr Surg 1986; 21 (10): 855–857.

    Article  CAS  Google Scholar 

  30. Clyman R, Cassady G, Kirklin JK, Collins M, Philips Iii JB . The role of patent ductus arteriosus ligation in bronchopulmonary dysplasia: reexamining a randomized controlled trial. J Pediatr 2009; 154 (6): 873–876.

    Article  Google Scholar 

  31. Malviya MN, Ohlsson A, Shah SS . Surgical versus medical treatment with cyclooxygenase inhibitors for symptomatic patent ductus arteriosus in preterm infants. Cochrane Database Syst Rev 2013; 3: Cd003951.

    Google Scholar 

  32. Benitz WE . Patent ductus arteriosus in preterm infants. Pediatrics 2016; 137 (1):e20153730.

    Article  Google Scholar 

  33. 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.e381.

    Article  Google Scholar 

  34. Aly H, Massaro AN, Patel K, El-Mohandes AA . Is it safer to intubate premature infants in the delivery room? Pediatrics 2005; 115 (6): 1660–1665.

    Article  Google Scholar 

  35. Patel RM, Kandefer S, Walsh MC, Bell EF, Carlo WA, Laptook AR et al. Causes and timing of death in extremely premature infants from 2000 through 2011. N Engl J Med 2015; 372 (4): 331–340.

    Article  CAS  Google Scholar 

  36. Aly H, Milner JD, Patel K, El-Mohandes AA . Does the experience with the use of nasal continuous positive airway pressure improve over time in extremely low birth weight infants? Pediatrics 2004; 114 (3): 697–702.

    Article  Google Scholar 

  37. Schmidt B, Davis P, Moddemann D, Ohlsson A, Roberts RS, Saigal S et al. Long-term effects of indomethacin prophylaxis in extremely-low-birth-weight infants. N Engl J Med 2001; 344 (26): 1966–1972.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Veronica Amaya for her assistance in editing the manuscript and making figures.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to H Aly.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mohamed, M., El-Dib, M., Alqahtani, S. et al. Patent ductus arteriosus in premature infants: to treat or not to treat?. J Perinatol 37, 652–657 (2017). https://doi.org/10.1038/jp.2017.4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/jp.2017.4

This article is cited by

Search

Quick links