SpringerLink
Log in

The effect of prolonged tracheal intubation on the association between patent ductus arteriosus and bronchopulmonary dysplasia (grades 2 and 3)

  • Article
  • Published:
Journal of Perinatology Submit manuscript

Abstract

Objective

To determine if the need for mechanical ventilation alters the association between prolonged patent ductus arteriosus (PDA) exposure and bronchopulmonary dysplasia (grades 2 and 3) (BPD).

Study Design

Observational study of 407 infants (<28 weeks’ gestation) with echocardiograms performed at planned intervals.

Results

Twelve percent (48/407) of study infants had BPD (grades 2 and 3). In a multivariable regression model, exposure to a moderate-to-large PDA shunt for ≥7 days was associated with an increased risk of BPD (grades 2 and 3) (from 16 to 35%: aRD = 19% (6, 32%), p < 0.005) when infants required ≥10 days of intubation (n = 170). In contrast, there was no significant association between prolonged PDA exposure and BPD when infants required ≤9 days of intubation (aRD = 4%) (−1, 10%) (n = 237).

Conclusions

Moderate-to-large PDAs are associated with an increased risk of BPD—but only when infants require intubation ≥10 days.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1: Flow diagram of patient entry into the study of BPD.
Fig. 2: Relationship between PDA exposure and the outcome BPD (grades 2 and 3).

Similar content being viewed by others

Data availability

The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. Hsu KH, Nguyen J, Dekom S, Ramanathan R, Noori S. Effects of patent ductus arteriosus on organ blood flow in infants born very preterm: a prospective study with serial echocardiography. J Pediatr. 2020;216:95–100.e102.

    Article  Google Scholar 

  2. Shimada S, Kasai T, Konishi M, Fujiwara T. Effects of patent ductus arteriosus on left ventricular output and organ blood flows in preterm infants with respiratory distress syndrome treated with surfactant. J Pediatr. 1994;125:270–7.

    Article  CAS  Google Scholar 

  3. Ledo A, Aguar M, Núñez-Ramiro A, Saénz P, Vento M. Abdominal near-infrared spectroscopy detects low mesenteric perfusion early in preterm infants with hemodynamic significant ductus arteriosus. Neonatology. 2017;112:238–45.

    Article  CAS  Google Scholar 

  4. 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;121:142–7.

    Article  Google Scholar 

  5. Szymankiewicz M, Hodgman JE, Siassi B, Gadzinowski J. Mechanics of breathing after surgical ligation of patent ductus arteriosus in newborns with respiratory distress syndrome. Biol Neonate. 2004;85:32–6.

    Article  Google Scholar 

  6. Gerhardt T, Bancalari E. Lung compliance in newborns with patent ductus arteriosus before and after surgical ligation. Biol Neonate. 1980;38:96–105.

    Article  CAS  Google Scholar 

  7. McCurnin D, Seidner S, Chang LY, Waleh N, Ikegami M, Petershack J, et al. Ibuprofen-induced patent ductus arteriosus closure: physiologic, histologic, and biochemical effects on the premature lung. Pediatrics. 2008;121:945–56.

    Article  Google Scholar 

  8. McCurnin D, Clyman RI. Effects of a patent ductus arteriosus on postprandial mesenteric perfusion in premature baboons. Pediatrics. 2008;122:e1262–7.

    Article  Google Scholar 

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

  10. Cooke L, Steer P, Woodgate P. Indomethacin for asymptomatic patent ductus arteriosus in preterm infants. Cochrane Database Syst Rev. 2003:CD003745.

  11. 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 

  12. 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:CD004213.

  13. 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  Google Scholar 

  14. Clyman RI, Liebowitz M, Kaempf J, Erdeve O, Bulbul A, Hakansson S, 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;205:41–8.

    Article  Google Scholar 

  15. 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  Google Scholar 

  16. Sellmer A, Bjerre JV, Schmidt MR, McNamara PJ, Hjortdal VE, Host B, et al. Morbidity and mortality in preterm neonates with patent ductus arteriosus on day 3. Arch Dis Child Fetal Neonatal Ed. 2013;98:F505–10.

    Article  Google Scholar 

  17. Clyman RI, Hills NK, Liebowitz M, Johng S. Relationship between duration of infant exposure to a moderate-to-large patent ductus arteriosus shunt and the risk of develo** bronchopulmonary dysplasia or death before 36 weeks. Am J Perinatol. 2020;37:216–23.

    Article  Google Scholar 

  18. Walsh MC, Yao Q, Gettner P, Hale E, Collins M, Hensman A, et al. Impact of a physiologic definition on bronchopulmonary dysplasia rates. Pediatrics. 2004;114:1305–11.

    Article  Google Scholar 

  19. Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med. 2001;163:1723–9.

    Article  CAS  Google Scholar 

  20. Ehrenkranz RA, Walsh MC, Vohr BR, Jobe AH, Wright LL, Fanaroff AA, et al. Validation of the National Institutes of Health consensus definition of bronchopulmonary dysplasia. Pediatrics. 2005;116:1353–60.

    Article  Google Scholar 

  21. Poindexter BB, Feng R, Schmidt B, Aschner JL, Ballard RA, Hamvas A, et al. Comparisons and limitations of current definitions of bronchopulmonary dysplasia for the prematurity and respiratory outcomes program. Ann Am Thorac Soc. 2015;12:1822–30.

    Article  Google Scholar 

  22. Onland W, Debray TP, Laughon MM, Miedema M, Cools F, Askie LM, et al. Clinical prediction models for bronchopulmonary dysplasia: a systematic review and external validation study. BMC Pediatr. 2013;13:207.

    Article  Google Scholar 

  23. Jensen EA, Dysart K, Gantz MG, McDonald S, Bamat NA, Keszler M, et al. The diagnosis of bronchopulmonary dysplasia in very preterm infants. an evidence-based approach. Am J Respir Crit Care Med. 2019;200:751–9.

    Article  CAS  Google Scholar 

  24. 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;157:381–7.

    Article  Google Scholar 

  25. El Hajjar M, Vaksmann G, Rakza T, Kongolo G, Storme L. Severity of the ductal shunt: a comparison of different markers. Arch Dis Child Fetal Neonatal Ed. 2005;90:F419–22.

    Article  CAS  Google Scholar 

  26. Liebowitz M, Clyman RI. Prophylactic indomethacin compared with delayed conservative management of the patent ductus arteriosus in extremely preterm infants: effects on neonatal outcomes. J Pediatr. 2017;187:119–26.

    Article  CAS  Google Scholar 

  27. Clyman RI, Wickremasinghe A, Merritt TA, Solomon T, McNamara P, Jain A, et al. Hypotension following patent ductus arteriosus ligation: the role of adrenal hormones. J Pediatr. 2014;164:1449–55.

    Article  CAS  Google Scholar 

  28. Liebowitz MC, Clyman RI. Predicting the need for home oxygen therapy in preterm infants born before 28 weeks’ gestation. Am J Perinatol. 2016;33:34–9.

    Article  Google Scholar 

  29. Fenton TR, Kim JH. A systematic review and meta-analysis to revise the Fenton growth chart for preterm infants. BMC Pediatr. 2013;13:59.

    Article  Google Scholar 

  30. Papile LA, Burstein J, Burstein R, Koffler H. Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weight < 1500 grams. J Pediatr. 1978;92:529–34.

    Article  CAS  Google Scholar 

  31. Bell MJ, Ternberg JL, Feigin RD, Keating JP, Marshall R, Barton L, et al. Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging. Ann Surg. 1978;187:1–7.

    Article  CAS  Google Scholar 

  32. Laughon MM, Langer JC, Bose CL, Smith PB, Ambalavanan N, Kennedy KA, et al. Prediction of bronchopulmonary dysplasia by postnatal age in extremely premature infants. Am J Respir Crit Care Med. 2011;183:1715–22.

    Article  Google Scholar 

  33. Mirza H, Garcia J, McKinley G, Hubbard L, Sensing W, Schneider J, et al. Duration of significant patent ductus arteriosus and bronchopulmonary dysplasia in extremely preterm infants. J Perinatol. 2019;39:1648–55.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We would like to thank Drs. Mark Cocalis, Laura Robertson, Michael Brook, Anita Moon-Grady, and Shabnam Peyvandi for their expert help in reading and interpreting the echocardiograms. We would also like to thank Drs. Melissa Liebowitz and Sandy Johng for their help with sections of the data analysis.

Funding

This work was supported by grant from the U.S. Public Health Service National Heart, Lung and Blood Institute (HL109199) and a gift from the Jamie and Bobby Gates Foundation.

Author information

Authors and Affiliations

  1. Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA

    Ronald I. Clyman

  2. Department of Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA, USA

    Ronald I. Clyman

  3. Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA

    Nancy K. Hills

  4. Department of Neurology, University of California San Francisco, San Francisco, CA, USA

    Nancy K. Hills

Authors
  1. Ronald I. Clyman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nancy K. Hills
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ronald I. Clyman.

Ethics declarations

Conflict of interest

We have no conflict of interests. Neither of the authors has any potential conflict of interest, real or perceived; Neither of the authors has any financial agreement with any company whose product figures prominently in the manuscript. There are no “sponsors” of this project. And there are no “sponsors” who have had a role in (1) study design; (2) the collection, analysis, and interpretation of data; (3) the writing of the report; and (4) the decision to submit the paper for publication. RIC wrote the first draft of the manuscript and no honorarium, grant, or other form of payment was given to anyone to produce the manuscript.

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

Clyman, R.I., Hills, N.K. The effect of prolonged tracheal intubation on the association between patent ductus arteriosus and bronchopulmonary dysplasia (grades 2 and 3). J Perinatol 40, 1358–1365 (2020). https://doi.org/10.1038/s41372-020-0718-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41372-020-0718-x

  • Springer Nature America, Inc.

Search

Navigation