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.

  • Article
  • Published:

Patent ductus arteriosus and spontaneous intestinal perforation in a cohort of preterm infants

Journal of Perinatology volume 42, pages 1649–1653 (2022)Cite this article

Subjects

Abstract

Objective

To assess whether either duration and magnitude of ductal shunt or medical treatment for patent ductus arteriosus (PDA) are related to spontaneous intestinal perforation (SIP).

Study design

Clinical charts of infants <29 weeks’ gestation born from 2006 to 2018 were reviewed. Echocardiographic examinations were evaluated according to McNamara and Sehgal’s staging system.

Results

A higher percentage of patients with SIP had a hemodynamically significant PDA (HSPDA) and was treated with either NSAIDs or paracetamol (79% vs 53% and 81% vs 54%, respectively). Among non-treated patients, we found a 1.32 increase in the odds of SIP per day of persistence of HSPDA. In the cohort of patients treated despite the absence of HSPDA, we found a 2.35 increase in the odds of SIP per dose of drug administered.

Conclusion

Both treating a non-HSPDA and leaving a HSPDA to its natural history seem to be associated with SIP.

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

Fig. 1: Inclusion flow diagram.

Similar content being viewed by others

References

  1. Aschner JL, Deluga KS, Metlay LA, Emmens RW, Hendricks-Munoz KD. Spontaneous focal gastrointestinal perforation in very low birth weight infants. J Pediatr. 1988;113:364–7.

    Article  CAS  PubMed  Google Scholar 

  2. Gordon PV. Understanding intestinal vulnerability to perforation in the extremely low birth weight infant. Pediatr Res. 2009;65:138–44.

    Article  PubMed  Google Scholar 

  3. Buchheit JQ, Stewart DL. Clinical comparison of localized intestinal perforation and necrotizing enterocolitis in neonates. Pediatrics. 1994;93:32–6.

    Article  CAS  PubMed  Google Scholar 

  4. Gordon PV, Attridge JT. Understanding clinical literature relevant to spontaneous intestinal perforations. Am J Perinatol. 2009;26:309–16.

    Article  PubMed  Google Scholar 

  5. Novack CM, Waffarn F, Sills JH, Pousti TJ, Warden MJ, Cunningham MD. Focal intestinal perforation in the extremely-low-birth-weight infant. J Perinatol. 1994;14:450–3.

    CAS  PubMed  Google Scholar 

  6. Okuyama H, Kubota A, Oue T, Kuroda S, Ikegami R, Kamiyama M. A comparison of the clinical presentation and outcome of focal intestinal perforation and necrotizing enterocolitis in very-low-birth-weight neonates. Pediatr Surg Int. 2002;18:704–6.

    Article  PubMed  Google Scholar 

  7. Vongbhavit K, Underwood MA. Intestinal perforation in the premature infant. J Neonatal Perinat Med. 2017;10:281–9.

    Article  CAS  Google Scholar 

  8. Pumberger W, Mayr M, Kohlhauser C, Weninger M. Spontaneous localized intestinal perforation in very-low-birth-weight infants: A distinct clinical entity different from necrotizing enterocolitis. J Am Coll Surg. 2002;195:796–803.

    Article  PubMed  Google Scholar 

  9. Wadhawan R, Oh W, Hintz SR, Blakely ML, Das A, Bell EF, et al. Neurodevelopmental outcomes of extremely low birth weight infants with spontaneous intestinal perforation or surgical necrotizing enterocolitis. J Perinatol. 2014;34:64–70.

    Article  PubMed  Google Scholar 

  10. Wadhawan R, Oh W, Vohr BR, Saha S, Das A, Bell EF, et al. Spontaneous intestinal perforation in extremely low birth weight infants: association with indometacin therapy and effects on neurodevelopmental outcomes at 18-22 months corrected age. Arch Dis Child Fetal Neonatal Ed. 2013;98:F127–32.

    Article  PubMed  Google Scholar 

  11. Sehgal A, McNamara PJ. The ductus arteriosus: a refined approach! Semin Perinatol. 2012;36:105–13.

    Article  PubMed  Google Scholar 

  12. Benitz WE. Treatment of persistent patent ductus arteriosus in preterm infants: time to accept the null hypothesis. J Perinatol. 2010;30:241–52.

    Article  CAS  PubMed  Google Scholar 

  13. El-Khuffash A, Weisz DE, McNamara PJ. Reflections of the changes in patent ductus arteriosus management during the last 10 years. Arch Dis Child Fetal Neonatal Ed. 2016;101:F474–8.

    Article  PubMed  Google Scholar 

  14. Sehgal A, McNamara PJ. Does echocardiography facilitate determination of hemodynamic significance attributable to the ductus arteriosus? Eur J Pediatr. 2009;168:907–14.

    Article  PubMed  Google Scholar 

  15. 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;26:93–9.

    Article  CAS  PubMed  Google Scholar 

  16. Bloom B. Attridge et al. present an analysis of a complex data set, which offers important confirmation of the differences between the clinical presentation of spontaneous intestinal perforations (SIP) and surgical necrotizing enterocolitis (NEC). J Perinatol. 2006;26:384–6.

    Article  CAS  PubMed  Google Scholar 

  17. Fujii AM, Brown E, Mirochnick M, O’Brien S, Kaufman G. Neonatal necrotizing enterocolitis with intestinal perforation in extremely premature infants receiving early indomethacin treatment for patent ductus arteriosus. J Perinatol. 2002;22:535–40.

    Article  PubMed  Google Scholar 

  18. Schmidt B, Davis P, Moddemann D, Ohlsson A, Roberts RS, Saigal S, et al. Long-term effects of indomethacin prophylaxis. N. Engl J Med. 2001;344:1966–72.

    Article  CAS  PubMed  Google Scholar 

  19. Sharma R, Hudak ML, Tepas JJ, Wludyka PS, Teng RJ, Hastings LK, et al. Prenatal or postnatal indomethacin exposure and neonatal gut injury associated with isolated intestinal perforation and necrotizing enterocolitis. J Perinatol. 2010;30:786–93.

    Article  CAS  PubMed  Google Scholar 

  20. Stark A, Carlo W, Tyson J, Papile L, Wright L, Shankaran S, et al. Adverse effects of early dexamethasone treatment in extremely-low-birth-weight infants. National Institute of Child Health and Human Development Neonatal Research Network. N. Engl J Med. 2001;344:95–101.

    Article  CAS  PubMed  Google Scholar 

  21. 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;114:1649–57.

    Article  PubMed  Google Scholar 

  22. Gournay V, Roze JC, Kuster A, Daoud P, Cambonie G, Hascoet JM, et al. Prophylactic ibuprofen versus placebo in very premature infants: a randomised, double-blind, placebo-controlled trial. Lancet. 2004;364:1939–44.

    Article  CAS  PubMed  Google Scholar 

  23. Kelleher J, Salas AA, Bhat R, Ambalavanan N, Saha S, Stoll BJ, et al. Prophylactic indomethacin and intestinal perforation in extremely low birth weight infants. Pediatrics. 2014;134:e1369–77.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Mitra S, Florez ID, Tamayo ME, Mbuagbaw L, Vanniyasingam T, Veroniki AA, 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. JAMA. 2018;319:1221–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Marconi E, Bettiol A, Ambrosio G, Perduca V, Vannacci A, Troiani S, et al. Efficacy and safety of pharmacological treatments for patent ductus arteriosus closure: a systematic review and network meta-analysis of clinical trials and observational studies. Pharm Res. 2019;148:104418.

    Article  CAS  Google Scholar 

  26. Ohlsson A, Shah PS. Paracetamol (acetaminophen) for patent ductus arteriosus in preterm or low-birth-weight infants. Cochrane Database Syst Rev. 2018;4:CD010061. https://doi.org/10.1002/14651858.CD010061.pub3.

  27. Shepherd JL, Noori S. What is a hemodynamically significant PDA in preterm infants? Congenit Heart Dis. 2019;14:21–6.

    PubMed  Google Scholar 

  28. McNamara PJ, Sehgal A. Towards rational management of the patent ductus arteriosus: the need for disease staging. Arch Dis Child Fetal Neonatal Ed. 2007;92:424–7.

    Article  Google Scholar 

  29. Schena F, Francescato G, Cappelleri A, Picciolli I, Mayer A, Mosca F, et al. Association between hemodynamically significant patent ductus arteriosus and bronchopulmonary dysplasia. J Pediatr. 2015;166:1488–92.

    Article  PubMed  Google Scholar 

  30. 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;31:465–70.

    Article  CAS  PubMed  Google Scholar 

  31. van Laere D, van Overmeire B, Gupta S, El Khuffash A, Savoia M, McNamara PJ, et al. Application of NPE in the assessment of a patent ductus arteriosus. Pediatr Res. 2018;84:46–56.

    Article  PubMed  PubMed Central  Google Scholar 

  32. O’Rourke DJ, El-Khuffash A, Moody C, Walsh K, Molloy EJ. Patent ductus arteriosus evaluation by serial echocardiography in preterm infants. Acta Paediatr. 2008;97:574–8.

    Article  PubMed  Google Scholar 

  33. El-Khuffash A, Barry D, Walsh K, Davis PG, Molloy EJ. Biochemical markers may identify preterm infants with a patent ductus arteriosus at high risk of death or severe intraventricular haemorrhage. Arch Dis Child Fetal Neonatal Ed. 2008;93:F407–12.

    Article  CAS  PubMed  Google Scholar 

  34. El-Khuffash AF, Amoruso M, Culliton M, Molloy EJ. N-terminal pro-B-type natriuretic peptide as a marker of ductal haemodynamic significance in preterm infants: a prospective observational study. Arch Dis Child Fetal Neonatal Ed. 2007;92:F421–2.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Chock VY, Rose LA, Mante JV, Punn R. Near-infrared spectroscopy for detection of a significant patent ductus arteriosus. Pediatr Res. 2016;80:675–80.

    Article  PubMed  Google Scholar 

  36. Arman D, Sancak S, Gürsoy T, Topcuoğlu S, Karatekin G, Ovalı F. The association between NIRS and Doppler ultrasonography in preterm infants with patent ductus arteriosus. J Matern Neonatal Med. 2020;33:1245–52.

    Article  Google Scholar 

  37. Lee JA. Practice for preterm patent ductus arteriosus; focusing on the hemodynamic significance and the impact on the neonatal outcomes. Korean J Pediatr. 2019;62:245–51.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Gursoy T, Hayran M, Derin H, Ovali F. A clinical scoring system to predict the development of bronchopulmonary dysplasia. Am J Perinatol. 2014;32:659–65.

    Article  PubMed  Google Scholar 

  39. El-Khuffash AF, Slevin M, McNamara PJ, Molloy EJ. Troponin T, N-terminal pro natriuretic peptide and a patent ductus arteriosus scoring system predict death before discharge or neurodevelopmental outcome at 2 years in preterm infants. Arch Dis Child Fetal Neonatal Ed. 2011;96:133–8.

    Article  Google Scholar 

  40. El-Khuffash A, James AT, Corcoran JD, Dicker P, Franklin O, Elsayed YN, et al. A patent ductus arteriosus severity score predicts chronic lung disease or death before discharge. J Pediatr. 2015;167:1354–61.

    Article  PubMed  Google Scholar 

  41. Sehgal A, Paul E, Menahem S. Functional echocardiography in staging for ductal disease severity: role in predicting outcomes. Eur J Pediatr. 2013;172:179–84.

    Article  PubMed  Google Scholar 

  42. Wyllie JP, Gupta S. Prophylactic and early targeted treatment of patent ductus arteriosus. Semin Fetal Neonatal Med. 2018;23:250–4.

    Article  PubMed  Google Scholar 

  43. Jasani B, Weisz DE, McNamara PJ. Evidence-based use of acetaminophen for hemodynamically significant ductus arteriosus in preterm infants. Semin Perinatol. 2018;42:243–52.

    Article  CAS  PubMed  Google Scholar 

  44. Meyer CL, Payne NR, Roback SA. Spontaneous, isolated intestinal perforations in neonates with birth weight <1,000 g not associated with necrotizing enterocolitis. J Pediatr Surg. 1991;26:714–7.

    Article  CAS  PubMed  Google Scholar 

  45. Adderson EE, Pappin A, Pavia AT. Spontaneous intestinal perforation in premature infants: a distinct clinical entity associated with systemic candidiasis. J Pediatr Surg. 1998;33:1463–7.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. NICU, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

    Alessandra Mayer, Gaia Francescato & Fabio Mosca

  2. Department of Statistics and Quantitative Methods, Division of Biostatistics, Epidemiology and Public Health, University of Milano-Bicocca, Milan, Italy

    Nicola Pesenti

  3. Neonatal Intensive Care Unit - AO SS Antonio e Biagio e C. Arrigo Hospital, Alessandria, Italy

    Federico Schena

  4. Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy

    Fabio Mosca

Authors
  1. Alessandra Mayer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gaia Francescato
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nicola Pesenti
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Federico Schena
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Fabio Mosca
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

AM, GF, NP, FS and FM contributed to the conception and the design of the manuscript. AM collected the data retrospectively. AM, NP and FS performed statistical analysis. AM and GF wrote the first draft of the manuscript. All authors contributed to manuscript critical revision, read and approved the submitted version.

Corresponding author

Correspondence to Gaia Francescato.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mayer, A., Francescato, G., Pesenti, N. et al. Patent ductus arteriosus and spontaneous intestinal perforation in a cohort of preterm infants. J Perinatol 42, 1649–1653 (2022). https://doi.org/10.1038/s41372-022-01403-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41372-022-01403-8

This article is cited by

Search

Advanced search

Quick links