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:

Echocardiographic prediction of severe pulmonary hypertension in neonates undergoing therapeutic hypothermia for hypoxic-ischemic encephalopathy

Journal of Perinatology volume 39, pages 1656–1662 (2019)Cite this article

Subjects

Abstract

Objective

Among neonates undergoing whole body cooling for hypoxic-ischemic encephalopathy (HIE), to compare ventricular function in the presence and absence of pulmonary hypertension (PPHN) needing inhaled nitric oxide (iNO)/ECMO.

Design

This retrospective study included infants with HIE who underwent cooling. ECHO (<24 h age) measures, RV fractional area change (FAC), RV Tricuspid annular plane systolic excursion (TAPSE), myocardial performance indices (MPI), and the RV systolic to diastolic duration (S/D) ratio were evaluated.

Results

The iNO/ECMO group (n = 26) had lower TAPSE and RV FAC and higher RV MPI and S/D, compared with controls (n = 39). Area under the curve was highest for RV S/D, with fair sensitivity (95% CI) [76.9 (56.3–91%)] and negative predictive value [78.6 (63.3–88.6%)] for subsequent iNO/ECMO at cutoff >1.45.

Conclusions

Infants with HIE undergoing cooling who progressed to iNO/ECMO for PPHN had RV dysfunction on early ECHO; S/D had the best predictive performance. RV S/D may be a useful early marker of PPHN in HIE.

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

Similar content being viewed by others

References

  1. Bryce J, Boschi-Pinto C, Shibuya K, Black RE. WHO estimates of the causes of death in children. Lancet. 2005;365:1147–52.

    Article  Google Scholar 

  2. Jacobs SE, Berg M, Hunt R, Tarnow-Mordi WO, Inder TE, Davis PG. Cooling for newborns with hypoxic ischaemic encephalopathy. Cochrane Database Syst Rev. 2013;1:CD003311.

  3. Tagin MA, Woolcott CG, Vincer MJ, Whyte RK, Stinson DA. Hypothermia for neonatal hypoxic ischemic encephalopathy. An updated systematic review and meta-analysis. Arch Pediatr Adolesc Med. 2012;166:558–66.

    Article  Google Scholar 

  4. Yum SK, Seo YM, Kwun Y, Moon CJ, Youn YA, Sung IK. Therapeutic hypothermia in infants with hypoxic–ischemic encephalopathy and reversible persistent pulmonary hypertension: short-term hospital outcomes. J Matern Fetal Neonatal Med. 2018;31:3108–14.

    Article  Google Scholar 

  5. Liu J, Feng ZC. Changes in pulmonary arterial pressure in term-infants with hypoxic-ischemic encephalopathy. Pediatr Int. 2009;51:786–9.

    Article  Google Scholar 

  6. Lapointe A, Barrington KJ. Pulmonary hypertension and the asphyxiated newborn. J Pediatr. 2011;158:e19–24.

    Article  Google Scholar 

  7. Fox WW, Duara S. Persistent pulmonary hypertension in the neonate: diagnosis and management. J Pediatr. 1983;103:505–14.

    Article  CAS  Google Scholar 

  8. Gersony WM, Morishima HO, Daniel SS, Kohl S, Cohen H, Brown W, et al. The hemodynamic effects of intrauterine hypoxia: an experimental model in newborn lambs. J Pediatr. 1976;89:631–5.

    Article  CAS  Google Scholar 

  9. Shankaran S, Laptook AR, Ehrenkranz RA, Tyson JE, McDonald SA, Donovan EF, et al. Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med. 2005;353:1574–84.

    Article  CAS  Google Scholar 

  10. Shankaran S, Laptook AR, Pappas A, McDonald SA, Das A, Tyson JE, et al. Effect of depth and duration of cooling on deaths in the NICU among neonates with hypoxic ischemic encephalopathy: a randomized clinical trial. J Am Med Assoc. 2014;312:2629–39.

    Article  CAS  Google Scholar 

  11. Azzopardi DV, Strohm B, Edwards AD, Dyet L, Halliday HL, Juszczak E, et al. Moderate hypothermia to treat perinatal asphyxial encephalopathy. N Engl J Med. 2009;361:1349–58.

    Article  CAS  Google Scholar 

  12. Eicher DJ, Wagner CL, Katikaneni LP, Hulsey TC, Bass WT, Kaufman DA, et al. Moderate hypothermia in neonatal encephalopathy: safety outcomes. Pediatr Neurol. 2005;32:18–24.

    Article  Google Scholar 

  13. Gagnon MH, Wintermark P. Effect of persistent pulmonary hypertension on brain oxygenation in asphyxiated term newborns treated with hypothermia. J Matern Fetal Neonatal Med. 2016;29:2049–55.

    Article  CAS  Google Scholar 

  14. Lopez L, Colan SD, Frommelt PC, Ensing GJ, Kendall K, Younoszai AK, et al. Recommendations for quantification methods during the performance of a pediatric echocardiogram: a report from the Pediatric Measurements Writing Group of the American Society of Echocardiography Pediatric and Congenital Heart Disease Council. J Am Soc Echocardiogr. 2010;23:465–95.

    Article  Google Scholar 

  15. Lammers AE, Haworth SG, Riley G, Maslin K, Diller GP, Marek J. Value of tissue Doppler echocardiography in children with pulmonary hypertension. J Am Soc Echocardiogr. 2012;25:504–10.

    Article  Google Scholar 

  16. Forfia PR, Fisher MR, Mathai SC, Housten-Harris T, Hemnes AR, Borlaug BA, et al. Tricuspid annular displacement predicts survival in pulmonary hypertension. Am J Respir Crit Care Med. 2006;174:1034–41.

    Article  Google Scholar 

  17. Ploegstra MJ, Roofthooft MTR, Douwes JM, Bartelds B, Elzenga NJ, van de Weerd D, et al. Echocardiography in pediatric pulmonary arterial hypertension: early study on assessing disease severity and predicting outcome. Circ Cardiovasc Imaging. 2015;8:e000878.

    Article  Google Scholar 

  18. Kassem E, Humpl T, Friedberg MK. Prognostic significance of 2-dimensional, M-mode, and Doppler echo indices of right ventricular function in children with pulmonary arterial hypertension. Am Heart J. 2013;165:1024–31.

    Article  Google Scholar 

  19. Aggarwal S, Stockman PT, Klein MD, Natarajan G. The right ventricular systolic to diastolic duration ratio: a simple prognostic marker in congenital diaphragmatic hernia? Acta Paediatr. 2011;100:1315–8.

    Article  Google Scholar 

  20. Aggarwal S, Natarajan G. Echocardiographic correlates of persistent pulmonary hypertension of the newborn. Early Hum Dev. 2015;91:285–9.

    Article  Google Scholar 

  21. Ichihashi K, Yada Y, Takahashi N, Honma Y, Momoi M. Utility of a Doppler-derived index combining systolic and diastolic performance (Tei index) for detecting hypoxic cardiac damage in newborns. J Perinat Med. 2005;33:549–5.

    PubMed  Google Scholar 

  22. Aggarwal S, Natarajan G. Biventricular function on early echocardiograms in neonatal hypoxic-ischaemic encephalopathy. Acta Paediatr. 2017;106:1085–90.

    Article  Google Scholar 

  23. Friedberg MK, Silverman NH. The systolic to diastolic duration ratio in children with hypoplastic left heart syndrome: a novel Doppler index of right ventricular function. J Am Soc Echocardiogr. 2007;20:749–55.

    Article  Google Scholar 

  24. Lakshminrusimha S, Shankaran S, Laptook A, McDonald S, Keszler M, Van Meurs K, et al. Pulmonary hypertension associated with hypoxic-ischemic encephalopathy-antecedent characteristics and comorbidities. J Pediatr. 2018;196:45–51.e3.

    Article  Google Scholar 

  25. More KS, Sakhuja P, Giesinger RE, Ting JY, Keyzers M, Sheth JN, et al. Cardiovascular Associations with Abnormal Brain Magnetic Resonance Imaging in Neonates with Hypoxic Ischemic Encephalopathy Undergoing Therapeutic Hypothermia and Rewarming. Am J Perinatol. 2018. https://doi.org/10.1055/s-0038-1629900.

    Article  Google Scholar 

  26. Abman SH, Hansmann G, Archer SL, Ivy DD, Adatia I, Chung WK, et al. Pediatric pulmonary hypertension: guidelines from the American Heart Association and American Thoracic Society. Circulation. 2015;132:2037–99.

    Article  Google Scholar 

  27. Mertens L, Seri I, Marek J, Arlettaz R, Barker P, McNamara P, et al. Targeted Neonatal Echocardiography in the Neonatal Intensive Care Unit: practice guidelines and recommendations for training. Writing Group of the American Society of Echocardiography (ASE) in collaboration with the European Association of Echocardiography (EAE) and the Association for European Pediatric Cardiologists (AEPC). J Am Soc Echocardiogr. 2011;24:1057–78.

    Article  Google Scholar 

  28. Richardson C, Amirtharaj C, Gruber D, Hayes DA. Assessing myocardial function in infants with pulmonary hypertension: the role of tissue Doppler imaging and tricuspid annular plane systolic excursion. Pediatr Cardiol. 2017;38:558–65.

    Article  Google Scholar 

  29. Sehgal A, Malikiwi A, Paul E, Tan K, Menahem S. Right ventricular function in infants with bronchopulmonary dysplasia: association with respiratory sequelae. Neonatology. 2016;109:289–96.

    Article  Google Scholar 

  30. Altit G, Bhombal S, Van Meurs K, Tacy TA. Ventricular performance is associated with need for extracorporeal membrane oxygenation in newborns with congenital diaphragmatic hernia. J Pediatr. 2017;191:28–34.

    Article  Google Scholar 

  31. Altit G, Bhombal S, Van Meurs K, Tacy TA. Diminished cardiac performance and left ventricular dimensions in neonates with congenital diaphragmatic hernia. Pediatr Cardiol. 2018;39:993–1000.

    Article  Google Scholar 

  32. Aggarwal S, Shanti C, Lelli J, Natarajan G. Prognostic utility of noninvasive estimates of pulmonary vascular compliance in neonates with congenital diaphragmatic hernia. J Pediatr Surg. 2018. https://doi.org/10.1016/j.jpedsurg.2018.08.057.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatrics, Wayne State University, Children’s Hospital of Michigan, Detroit, MI, USA

    Sanjeev Aggarwal, Prashant Agarwal & Girija Natarajan

Authors
  1. Sanjeev Aggarwal
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Prashant Agarwal
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Girija Natarajan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Girija Natarajan.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

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

Prior Presentation: Poster presentation, Annual Conference, Society of Pediatric Research, May 2018, Toronto, Canada

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Aggarwal, S., Agarwal, P. & Natarajan, G. Echocardiographic prediction of severe pulmonary hypertension in neonates undergoing therapeutic hypothermia for hypoxic-ischemic encephalopathy. J Perinatol 39, 1656–1662 (2019). https://doi.org/10.1038/s41372-019-0442-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41372-019-0442-6

This article is cited by

Search

Advanced search

Quick links