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:

Phenotyping respiratory decompensation following definitive closure of the patent ductus arteriosus in preterm infants

Journal of Perinatology volume 42, pages 649–654 (2022)Cite this article

Abstract

Objective

To identify risk factors associated with high-frequency ventilation (HFV) following definitive closure of the patent ductus arteriosus (PDA).

Methods

We performed a retrospective study of premature infants (<37 weeks) who were mechanically ventilated before and after surgical or transcatheter PDA closure. Primary outcome was HFV requirement within 24 h of procedure. Logistic regression was used to estimate clinical associations with post procedure HFV requirement.

Results

We identified 110 infants who were mechanically ventilated before PDA closure, of which 48 (44%) escalated to HFV within 24 h after closure. In the multivariable model, surgical ligation (OR 21.5, 95% CI 1.6–284), elevated Respiratory Severity Score (RSS) 1 h post-procedure (OR 1.78, 95% CI 1.07–2.99) and 12 h post-procedure (OR 2.12, 95% CI 1.37–3.26) were independent predictors of HFV.

Conclusion

Surgical ligation and elevated RSS values over the first 12 h after PDA closure are risk factors for HFV.

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: Predicted probability curves of high-frequency ventilation according to Respiratory Severity Score (RSS) were derived using logistic regression.

Similar content being viewed by others

References

  1. Rios DR, Bhattacharya S, Levy PT, McNamara PJ. Circulatory insufficiency and hypotension related to the ductus arteriosus in neonates. Front Pediatr. 2018;6:62.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Serrano RM, Madison M, Lorant D, Hoyer M, Alexy R. Comparison of ‘post-patent ductus arteriosus ligation syndrome’ in premature infants after surgical ligation vs. percutaneous closure. J Perinatol. 2020;40:324–9.

    Article  PubMed  Google Scholar 

  3. Nealon E, Rivera BK, Cua CL, Ball MK, Stiver C, Boe BA, et al. Follow-up after Percutaneous Patent Ductus Arteriosus Occlusion in Lower Weight Infants. J Pediatr: Elsevier Inc; 2019. pp. 144–50.e143.

  4. Willson DF, Thomas NJ, Markovitz BP, Bauman LA, DiCarlo JV, Pon S, et al. Effect of exogenous surfactant (calfactant) in pediatric acute lung injury: a randomized controlled trial. JAMA. 2005;293:470–6.

    Article  CAS  PubMed  Google Scholar 

  5. Stewart DL, Dela Cruz TV, Duncan SD, Cook LN. Response to high frequency jet ventilation may predict the need for extracorporeal membrane oxygenation. Eur Respir J. 1996;9:1257–60.

    Article  CAS  PubMed  Google Scholar 

  6. Golombek SG, Young JN. Efficacy of inhaled nitric oxide for hypoxic respiratory failure in term and late preterm infants by baseline severity of illness: a pooled analysis of three clinical trials. Clin Ther. 2010;32:939–48.

    Article  CAS  PubMed  Google Scholar 

  7. Shahid S, Dutta S, Symington A, Shivananda S, McMaster University N. Standardizing umbilical catheter usage in preterm infants. Pediatrics. 2014;133:e1742–1752.

    Article  PubMed  Google Scholar 

  8. de Brito CS, de Brito DV, Abdallah VO, Gontijo, Filho PP. Occurrence of bloodstream infection with different types of central vascular catheter in critically neonates. J Infect. 2010;60:128–32.

    Article  PubMed  Google Scholar 

  9. Deindl P, Waldhor T, Unterasinger L, Berger A, Keck M. Arterial catheterisation in neonates can result in severe ischaemic complications but does not impair long-term extremity function. Acta Paediatr. 2018;107:240–8.

    Article  PubMed  Google Scholar 

  10. Iyer NP, Mhanna MJ. Non-invasively derived respiratory severity score and oxygenation index in ventilated newborn infants. Pediatric Pulmonol. 2013;48:364–9.

    Article  Google Scholar 

  11. Malkar MB, Gardner WP, Mandy GT, Stenger MR, Nelin LD, Shepherd EG, et al. Respiratory severity score on day of life 30 is predictive of mortality and the length of mechanical ventilation in premature infants with protracted ventilation. Pediatric Pulmonol. 2015;50:363–9.

    Article  Google Scholar 

  12. Seo YM, Sung IK, Yum SK. Risk factors associated with prolonged mechanical ventilation after surgical patent ductus arteriosus ligation in preterm infants. J Matern Fetal Neonatal Med. 2020;8:1–8.

  13. Ting JY, Resende M, More K, Nicholls D, Weisz DE, El-Khuffash A, et al. Predictors of respiratory instability in neonates undergoing patient ductus arteriosus ligation after the introduction of targeted milrinone treatment. J Thoracic Cardiovasc Surg. 2016;152:498–504.

    Article  Google Scholar 

  14. Hsu KH, Wong P, Ram Kumar S, Evans J, Noori S. Predictors of respiratory improvement 1 week after ligation of patent ductus arteriosus in preterm infants. J Pediatr. 2019;205:49–54 e42.

    Article  PubMed  Google Scholar 

  15. Francis JV, Padmanabhan S, Jaques L, Courtot J, Sehgal A. Respiratory and cardiovascular morbidity in the first 48 h post surgical ligation of the patent ductus arteriosus. J Neonatal-Perinatal Med. 2011;4:21–6.

    Article  Google Scholar 

  16. Philip R, Waller BR, Chilakala S, Graham B, Stecchi N, Apalodimas L, et al. Hemodynamic and clinical consequences of early versus delayed closure of patent ductus arteriosus in extremely low birth weight infants. J Perinatol. 2021;41:100–8.

    Article  CAS  PubMed  Google Scholar 

  17. Rodriguez Ogando A, Planelles Asensio I, de la Blanca ARS, Ballesteros Tejerizo F, Sanchez Luna M, Gil Jaurena JM, et al. Surgical ligation versus percutaneous closure of patent ductus arteriosus in very low-weight preterm infants: which are the real benefits of the percutaneous approach? Pediatric Cardiol. 2018;39:398–410.

    Article  CAS  Google Scholar 

  18. Regan W, Benbrik N, Sharma SR, Auriau J, Bouvaist H, Bautista-Rodriguez C, et al. Improved ventilation in premature babies after transcatheter versus surgical closure of patent ductus arteriosus. Int J Cardiol. 2020;311:22–7.

  19. Schwartz MC, Nykanen D, Winner LH, Perez J, McMahan M, Munro HM, et al. Transcatheter patent ductus arteriosus occlusion in small infants. Congenit Heart Dis. 2016;11:647–55.

  20. Sathanandam S, Balduf K, Chilakala S, Washington K, Allen K, Knott-Craig C, et al. Role of Transcatheter patent ductus arteriosus closure in extremely low birth weight infants. Catheter Cardiovasc Interv. 2019;93:89–96.

    Article  PubMed  Google Scholar 

  21. Abu Hazeem AA, Gillespie MJ, Thun H, Munson D, Schwartz MC, Dori Y, et al. Percutaneous closure of patent ductus arteriosus in small infants with significant lung disease may offer faster recovery of respiratory function when compared to surgical ligation. Catheter Cardiovasc Interv. 2013;82:526–33.

    PubMed  Google Scholar 

  22. Ulrich TJB, Hansen TP, Reid KJ, Bingler MA, Olsen SL. Post-ligation cardiac syndrome is associated with increased morbidity in preterm infants. J Perinatol. 2018;38:537–42.

    Article  PubMed  Google Scholar 

  23. Harting MT, Blakely ML, Cox CS Jr., Lantin-Hermoso R, Andrassy RJ, Lally KP. Acute hemodynamic decompensation following patent ductus arteriosus ligation in premature infants. J Invest Surg. 2008;21:133–8.

    Article  PubMed  Google Scholar 

  24. 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 e1441.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Jain A, Sahni M, El-Khuffash A, Khadawardi E, Sehgal A, McNamara PJ. Use of targeted neonatal echocardiography to prevent postoperative cardiorespiratory instability after patent ductus arteriosus ligation. J Pediatr. 2012;160:584–9 e581.

    Article  PubMed  Google Scholar 

  26. Wheeler CR, Stephens H, O’Donnell I, Zurakowski D, Smallwood CD. Mortality risk factors in preterm infants treated with high-frequency jet ventilation. Respiratory Care. 2020;65:1631–40.

    Article  PubMed  Google Scholar 

  27. Wheeler CR, Smallwood CD, O’Donnell I, Gagner D, Sola-Visner MC. Assessing initial response to high-frequency jet ventilation in premature infants with hypercapnic respiratory failure. Respiratory Care. 2017;62:867–72.

    Article  PubMed  Google Scholar 

  28. Sathanandam SK, Gutfinger D, O’Brien L, Forbes TJ, Gillespie MJ, Berman DP, et al. Amplatzer Piccolo Occluder clinical trial for percutaneous closure of the patent ductus arteriosus in patients ≥700 grams. Catheter Cardiovasc Interv. 2020;96:1–11.

  29. Hosmer DW, Lemeshow S, Sturdivant RX. Applied logistic regression, Third edition/edn. Wiley: Hoboken, New Jersey, 2013.

  30. Zhou X-h, McClish DK, Obuchowski NA. Statistical methods in diagnostic medicine, 2nd edn. Wiley: Hoboken, N.J., 2011.

  31. Staffa SJ, Zurakowski D. Statistical power and sample size calculations: A primer for pediatric surgeons. J Pediatr Surg: Elsevier Inc.; 2020. pp. 1173–9.

  32. Hamrick SEG, Sallmon H, Rose AT, Porras D, Shelton EL, reese J, et al. Patent Ductus Arteriosus of the Preterm Infant. Pediatrics; 2020. pp. 1–17.

  33. Shah SI, Aboudi D, La Gamma EF, Brumberg HL. Respiratory Severity Score greater than or equal to 2 at birth is associated with an increased risk of mortality in infants with birth weights less than or equal to 1250 g. Pediatric Pulmonol. 2020;55:3304–11.

    Article  Google Scholar 

  34. Indrani B, Anirudha D, Marc C, Hany A. Predicting outcomes of mechanically ventilated premature infants using respiratory severity score. Taylor & Francis; 2020. pp. 1–9.

  35. Jung YH, Jang J, Kim H-S, Shin SH, Choi CW, Kim E-K, et al. Respiratory severity score as a predictive factor for severe bronchopulmonary dysplasia or death in extremely preterm infants. BMC Pediatrics; 2019;28:1–8.

  36. Malkar MB, Gardner WP, Mandy GT, Stenger MR, Nelin LD, Shepherd EG, et al. Respiratory Severity Score on Day of Life 30 is Predictive of Mortality and the Length of Mechanical Ventilation in Premature Infants With Protracted Ventilation. Pediatric Pulmonol; 2015;140:363–9.

  37. Teixeira LS, Shivananda SP, Stephens D, Van Arsdell G, McNamara PJ. Postoperative cardiorespiratory instability following ligation of the preterm ductus arteriosus is related to early need for intervention. J Perinatol. 2008;28:803–10.

    Article  CAS  PubMed  Google Scholar 

  38. McNamara PJ, Stewart L, Shivananda SP, Stephens D, Sehgal A. Patent ductus arteriosus ligation is associated with impaired left ventricular systolic performance in premature infants weighing less than 1000 g. J Thorac Cardiovasc Surg. 2010;140:150–7.

    Article  PubMed  Google Scholar 

  39. Noori S, Friedlich P, Seri I, Wong P. Changes in myocardial function and hemodynamics after ligation of the ductus arteriosus in preterm infants. J Pediatr. 2007;150:597–602.

    Article  PubMed  Google Scholar 

  40. Giesinger RE. Impaired right ventricular function is associated with adverse outcome following hypoxic ischemic encephalopathy. Am J Respir Crit Care Med. 2019. pp. 1–48.

  41. Halliday M, Kavarana M, Ebeling M, Kiger J. Milrinone use for hemodynamic instability in patent ductus arteriosus ligation. J Matern Fetal Neonatal Med. 2017;30:529–33.

    Article  CAS  PubMed  Google Scholar 

  42. Moin F, Kennedy KA, Moya FR. Risk factors predicting vasopressor use after patent ductus arteriosus ligation. Amer J Perinatol. 2003;43:313–20.

  43. Natarajan G, Chawla S, Aggarwal S. Short-term outcomes of patent ductus arteriosus ligation in preterm neonates: reason for concern? Amer J Perinatol. 2010;150:431–7.

  44. Naik-Mathuria B, Chang S, Fitch ME, Westhoff J, Brandt ML, Ayres NA, et al. Patent ductus arteriosus ligation in neonates: preoperative predictors of poor postoperative outcomes. J Pediatr Surg. 2008;140:1100–5.

  45. McNamara PJ, Stewart L, Shivananda SP, Stephens D, Sehgal A. Patent ductus arteriosus ligation is associated with impaired left ventricular systolic performance in premature infants weighing less than 1000 g. J Thorac Cardiovasc Surg. 2010;162:150–7.

  46. Townsel CD, Emmer SF, Campbell WA, Hussain N. Gender differences in respiratory morbidity and mortality of preterm neonates. Front Pediatr. 2017;5:6.

    Article  PubMed  PubMed Central  Google Scholar 

  47. EL-Khuffash AF, Jain A, McNamara PJ. Ligation of the patent ductus arteriosus in preterm infants: understanding the physiology. J Pediatr. 2013;40:1100–6.

  48. Bernal JL, Cummins S, Gasparrini A. Interrupted time series regression for the evaluation of public health interventions: a tutorial. Int J Epidemiol. 2017;46:348–55.

    PubMed  Google Scholar 

  49. Clyman RI, Hills NK. The effect of prolonged tracheal intubation on the association between patent ductus arteriosus and bronchopulmonary dysplasia (grades 2 and 3). J Perinatol. 2020;40:1358–65.

    Article  PubMed  PubMed Central  Google Scholar 

  50. 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 developing bronchopulmonary dysplasia or death before 36 weeks. Am J Perinatol. 2020;37:216–23.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Respiratory Care, Boston Children’s Hospital, Boston, MA, USA

    Craig R. Wheeler, Daniel Gagner, Holly Stephens & Amelia Kraus

  2. Departments of Anesthesiology, Critical Care and Pain Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA

    David Zurakowski & Juan C. Ibla

  3. Department of Cardiology, Boston Children’s Hospital and Harvard Medical School, Boston, MA, USA

    Kevin G. Friedman, Ryan Callahan & Diego Porras

  4. Division of Newborn Medicine, Department of Pediatrics, Boston Children’s Hospital, Harvard Medical School, Harvard University, Boston, MA, USA

    Philip T. Levy

Authors
  1. Craig R. Wheeler
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Daniel Gagner
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Holly Stephens
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Amelia Kraus
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. David Zurakowski
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kevin G. Friedman
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Juan C. Ibla
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ryan Callahan
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Diego Porras
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Philip T. Levy
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

CRW and PTL devised the study protocol and analysis plan which was approved by all authors. DG, HS, and AK collected data. DZ provided expert assistance with statistical analysis and interpretation. JCI, KGF, RC and DP provided anesthesia, cardiology and procedural expertise. All of the listed authors made substantial contributions either to the conception of the study, data acquisition, analysis and interpretation of data. CRW and PTL wrote the first draft, but all listed authors critically revised it for intellectual content and approved the final version of the manuscript and have agreed to be accountable for all aspects of the work.

Corresponding author

Correspondence to Philip T. Levy.

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.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wheeler, C.R., Gagner, D., Stephens, H. et al. Phenotyping respiratory decompensation following definitive closure of the patent ductus arteriosus in preterm infants. J Perinatol 42, 649–654 (2022). https://doi.org/10.1038/s41372-021-01226-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41372-021-01226-z

Search

Advanced search

Quick links