Article | Published:

Post-ligation cardiac syndrome is associated with increased morbidity in preterm infants

Journal of Perinatologyvolume 38pages537542 (2018) | Download Citation



The influence of post-ligation cardiac syndrome (PLCS), a complication of patent ductus arteriosus (PDA) ligations, on neonatal outcomes is unknown. The purpose of this study was to determine the risks of PLCS on severe pulmonary morbidity and severe retinopathy of prematurity (ROP).

Study design

Retrospective cohort study of infants who underwent a PDA ligation between 2006 and 2015. Data were collected on patients with and without PLCS. The primary outcome was the difference in severe bronchopulmonary dysplasia (BPD) between groups. Secondary outcomes included discharge with home oxygen and severe ROP.


A total of 100 infants that underwent PDA ligation during the study period were included in the study; 31 (31%) neonates developed PLCS. In adjusted analysis, PLCS was associated with increased risk for severe BPD (RR 1.67, 95% CI: 1.15–2.42) and home oxygen therapy (RR: 1.47, 95% CI: 1.09–1.99) only. No association with severe ROP was seen (RR: 1.48; 95% CI: 0.87–2.52).


PLCS is associated with severe neonatal pulmonary morbidity, but not with severe ROP. Further investigation is warranted to validate these results.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. 1.

    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:e138–44.

  2. 2.

    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.

  3. 3.

    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:F235–239.

  4. 4.

    Lokku A, Mirea L, Lee SK, Shah PS. Trends and outcomes of patent ductus arteriosus treatment in very preterm infants in Canada. Am J Perinatol. 2016;34:441–50.

  5. 5.

    Weinberg JG, Evans FJ, Burns KM, Pearson GD, Kaltman JR. Surgical ligation of patent ductus arteriosus in premature infants: trends and practice variation. Cardiol Young. 2016;26:1107–14.

  6. 6.

    Kulkarni A, Richards J, Duffy D. Survey of management of patent ductus arteriosus in neonatal units across England. Arch Dis Child Fetal Neonatal Ed. 2013;98:F465–466.

  7. 7.

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

  8. 8.

    Bourgoin L, Cipierre C, Hauet Q, Basset H, Gournay V, Roze JC, et al. Neurodevelopmental outcome at 2 years of age according to patent ductus arteriosus management in very preterm infants. Neonatology. 2016;109:139–46.

  9. 9.

    Chorne N, Leonard C, Piecuch R, Clyman RI. Patent ductus arteriosus and its treatment as risk factors for neonatal and neurodevelopmental morbidity. Pediatrics. 2007;119:1165–74.

  10. 10.

    Clyman R, Cassady G, Kirklin JK, Collins M, Philips JB 3rd. The role of patent ductus arteriosus ligation in bronchopulmonary dysplasia: reexamining a randomized controlled trial. J Pediatr. 2009;154:873–6.

  11. 11.

    Baud O, Maury L, Lebail F, Ramful D, El Moussawi F, Nicaise C, et al. Effect of early low-dose hydrocortisone on survival without bronchopulmonary dysplasia in extremely preterm infants (PREMILOC): a double-blind, placebo-controlled, multicentre, randomised trial. Lancet. 2016;387:1827–36.

  12. 12.

    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;150:229–34. 234.e221

  13. 13.

    Weisz DE, More K, McNamara PJ, Shah PS. PDA ligation and health outcomes: a meta-analysis. Pediatrics. 2014;133:e1024–1046.

  14. 14.

    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;160:584–89. e581

  15. 15.

    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.

  16. 16.

    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.

  17. 17.

    Zou G. A modified poisson regression approach to prospective studies with binary data. Am J Epidemiol. 2004;159:702–6.

  18. 18.

    Chang LY, McCurnin D, Yoder B, Shaul PW, Clyman RI. Ductus arteriosus ligation and alveolar growth in preterm baboons with a patent ductus arteriosus. Pediatr Res. 2008;63:299–302.

  19. 19.

    Waleh N, McCurnin DC, Yoder BA, Shaul PW, Clyman RI. Patent ductus arteriosus ligation alters pulmonary gene expression in preterm baboons. Pediatr Res. 2011;69:212–6.

  20. 20.

    El-Khuffash AF, Jain A, McNamara PJ. Ligation of the patent ductus arteriosus in preterm infants: understanding the physiology. J Pediatr. 2013;162:1100–6.

  21. 21.

    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. e1

  22. 22.

    Satpute MD, Donohue PK, Vricella L, Aucott SW. Cardiovascular instability after patent ductus arteriosus ligation in preterm infants: the role of hydrocortisone. J Perinatol. 2012;32:685–9.

  23. 23.

    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.

  24. 24.

    El-Khuffash AF, Jain A, Dragulescu A, McNamara PJ, Mertens L. Acute changes in myocardial systolic function in preterm infants undergoing patent ductus arteriosus ligation: a tissue Doppler and myocardial deformation study. J Am Soc Echocardiogr. 2012;25:1058–67.

  25. 25.

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

  26. 26.

    Sehgal A, Francis JV, Lewis AI. Use of milrinone in the management of haemodynamic instability following duct ligation. Eur J Pediatr. 2011;170:115–9.

Download references

Author information


  1. Department of pediatrics, Children’s Mercy Hospital, Kansas City, MO, USA

    • Timothy J. B. Ulrich
    • , Taylor P. Hansen
    •  & Steven L. Olsen
  2. Department of Health Services and Outcomes Research, Children’s Mercy Hospital, Kansas City, MO, USA

    • Kimberly J. Reid
  3. Cardiac Center, Nemours Children’s Hospital, Orlando, FL, USA

    • Michael A. Bingler


  1. Search for Timothy J. B. Ulrich in:

  2. Search for Taylor P. Hansen in:

  3. Search for Kimberly J. Reid in:

  4. Search for Michael A. Bingler in:

  5. Search for Steven L. Olsen in:

Conflict of interest

The authors declare that they have no conflict of interest.

Corresponding author

Correspondence to Timothy J. B. Ulrich.

About this article

Publication history