Skip to main content

Advertisement

SpringerLink
Log in

Evaluation and Monitoring of Pulmonary Hypertension in Neonates With Congenital Diaphragmatic Hernia

  • Pediatric and Congenital Heart Disease (G Singh, Section Editor)
  • Published:
Current Treatment Options in Cardiovascular Medicine Aims and scope Submit manuscript

Abstract

Purpose of review

This review aims to describe the assessment of pulmonary hypertension and ventricular function in neonates with congenital diaphragmatic hernia and the long-term follow-up of their pulmonary vascular disease.

Recent findings

In 2015, the pediatric pulmonary hypertension guidelines from the American Heart Association and American Thoracic Society suggested class I level of evidence B guidelines for routine evaluation of patients with congenital diaphragmatic hernia, including longitudinal care in an interdisciplinary pulmonary hypertension program and following the recommendations offered for all children with pulmonary hypertension.

Summary

Congenital diaphragmatic hernia causes compression of the lungs during critical stages of fetal development and results in lung hypoplasia. As a result, there is abnormal development of pulmonary vasculature that leads to post-natal pulmonary hypertension and increased afterload to the right ventricle. Left ventricular filling is affected by decreased pre-load and mechanical compression by abdominal content leading to decreased systemic perfusion. Persistent pulmonary hypertension after surgical repair of congenital diaphragmatic hernia is associated with increased mortality. Assessment and monitoring of pulmonary hypertension and ventricular function in this population of neonates is crucial to determine response to medical treatment, the need for extracorporeal membrane oxygenation, and the timing of surgical repair.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Putnam L, Harting M, Tsao K, Morini F, Yoder B, Luco M, et al. Postdischarge follow-up of infants with congenital diaphragmatic hernia. Pediatrics. 2008;121:627–32.

    Article  Google Scholar 

  2. Moyer VA, Moya FR, Tibboel D, Losty PD, Nagaya M, Lally KP. Late versus early surgical correction for congenital diaphragmatic hernia in newborn infants. Cochrane Database Syst Rev. 2000;3:CD001695.

    Google Scholar 

  3. Madenci AL, Church JT, Gajarski RJ, Marchetti K, Klein EJ, Coughlin MA, et al. Pulmonary hypertension in patients with congenital diaphragmatic hernia: does lung size matter? Eur J Pediatr Surg. 2018;28:508–14.

    Article  Google Scholar 

  4. Kinsella JP, Ivy DD, Abman SH. Pulmonary vasodilator therapy in congenital diaphragmatic hernia: acute, late, and chronic pulmonary hypertension. Semin Perinatol. 2005;29:123–8.

    Article  Google Scholar 

  5. Leeuwen L, Fitzgerald DA. Congenital diaphragmatic hernia. J Paediatr Child Health. 2014;50:667–70.

    Article  Google Scholar 

  6. Balayla J, Abenhaim HA. Incidence, predictors and outcomes of congenital diaphragmatic hernia: a population-based study of 32 million births in the United States. J Matern Neonatal Med. 2014;27:1438–44.

    Article  Google Scholar 

  7. Mcgivern MR, Best KE, Rankin J, Wellesley D, Greenlees R, Addor M-C, et al. Epidemiology of congenital diaphragmatic hernia in Europe: a register-based study. Arch Dis Child Fetal Neonatol Ed. 2015;100:F137–44.

    Article  Google Scholar 

  8. Langham MR, Kays DW, Ledbetter DJ, Frentzen B, Sanford LL, Richards DS. Congenital diaphragmatic hernia. Epidemiology and outcome. Clin Perinatol. 1996;23:671–88.

    Article  Google Scholar 

  9. Levison J, Halliday R, Holland AJA, Walker K, Williams G, Shi E, et al. A population-based study of congenital diaphragmatic hernia outcome in New South Wales and the Australian Capital Territory, Australia, 1992-2001. J Pediatr Surg. 2006;41:1049–53.

    Article  Google Scholar 

  10. Torfs C, Curry C, Bateson T, Honore L. A population-based study of congenital diaphragmatic hernia. Teratology. 1992;46:555–65.

    Article  CAS  Google Scholar 

  11. •• Kardon G, Ackerman KG, McCulley DJ, Shen Y, Wynn J, Shang L, et al. Congenital diaphragmatic hernias: from genes to mechanisms to therapies. Dis Model Mech. 2017;10:955–70 This study offers a comprehensive review of embryology of CDH, genetic associations, cardiopulmonary consequences of CDH, and a brief review of current and emerging therapies.

    Article  CAS  Google Scholar 

  12. Graziano JN. Cardiac anomalies in patients with congenital diaphragmatic hernia and their prognosis: a report from the Congenital Diaphragmatic Hernia Study Group. J Pediatr Surg. 2005;40:1045–50.

    Article  Google Scholar 

  13. •• Harting MT. Congenital diaphragmatic hernia-associated pulmonary hypertension. Semin Pediatr Surg 2. 2017;26:147–53 A concise review of the role of signaling pathways and larger anatomical changes in PH, along with diagnostics and treatments for CDH-PH.

    Article  Google Scholar 

  14. del Cerro MJ, Abman S, Diaz G, Freudenthal AH, Freudenthal F, Harikrishnan S, et al. A consensus approach to the classification of pediatric pulmonary hypertensive vascular disease: report from the PVRI Pediatric Taskforce, Panama 2011. Pulm Circ. 2011;1:286–98.

    Article  Google Scholar 

  15. •• 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.e1 This study demonstrates the association between decreased right and left ventricular systolic functions with a need for extracorporeal membrane oxygenation support.

    Article  Google Scholar 

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

    Article  Google Scholar 

  17. Vonk Noordegraaf A, Westerhof BE, Westerhof N. The relationship between the right ventricle and its load in pulmonary hypertension. J Am Coll Cardiol. 2017;69:236–43.

    Article  Google Scholar 

  18. Tanaka T, Inamura N, Ishii R, Kayatani F, Yoneda A, Tazuke Y, et al. The evaluation of diastolic function using the diastolic wall strain (DWS) before and after radical surgery for congenital diaphragmatic hernia. Pediatr Surg Int. 2015;31:905–10.

    Article  Google Scholar 

  19. Putnam LR, Harting MT, Tsao K, Morini F, Yoder BA, Luco M, et al. Congenital diaphragmatic hernia study group. Congenital diaphragmatic hernia defect size and infant morbidity at discharge. Pediatrics. 2016;138:5.

  20. Burgos CM, Modée A, Öst E, Frenckner B. Addressing the causes of late mortality in infants with congenital diaphragmatic hernia. J Pediatr Surg. 2017;52:526–9.

    Article  Google Scholar 

  21. •• Abman SH, Hansmann G, Archer SL, Ivy DD, Adatia I, Chung WK, et al. Pediatric pulmonary hypertension. Circulation. 2015;132:2037–99 Summary of the most current AHA/ATS guidelines for the definition, evaluation, and management of PH in children.

    Article  Google Scholar 

  22. Barst RJ. Pharmacologically induced pulmonary vasodilatation in children and young adults with primary pulmonary hypertension. Chest. 1986;89:497–503.

    Article  CAS  Google Scholar 

  23. •• Wong M, Reyes J, Lapidus-Krol E, Chiang M, Humpl T, Al-Faraj M, et al. Pulmonary hypertension in congenital diaphragmatic hernia patients: prognostic markers and long-term outcomes. J Pediatr Surg. 2018;53:918–24 This study found that O/E LHR, liver herniation, and patch repair negatively correlated with persistent PH in highest-risk survivors in infancy but not long-term outcomes.

    Article  Google Scholar 

  24. Mourani PM, Sontag MK, Younoszai A, Ivy DD, Abman SH. Clinical utility of echocardiography for the diagnosis and management of pulmonary vascular disease in young children with chronic lung disease. Pediatrics. 2008;121:317–25.

    Article  Google Scholar 

  25. Patel SG, Woolman P, Li L, Craft M, Danford DA, Kutty S. Relation of right atrial volume, systemic venous dimensions, and flow patterns to right atrial pressure in infants and children. Am J Cardiol. 2017;119:1473–8.

    Article  Google Scholar 

  26. •• Lusk LA, Wai KC, Moon-Grady AJ, Steurer MA, Keller RL. Persistence of pulmonary hypertension by echocardiography predicts short-term outcomes in congenital diaphragmatic hernia. J Pediatr. 2015;166:251–256.e1 This study of a large cohort of neonates with CDH that describes the natural history of neonates with CDH who have persistent pulmonary hypertension after surgical repair.

    Article  Google Scholar 

  27. Currie PJ, Seward JB, Chan KL, Fyfe DA, Hagler DJ, Mair DD, et al. Continuous wave Doppler determination of right ventricular pressure: a simultaneous Doppler-catheterization study in 127 patients. J Am Coll Cardiol. 1985;6:750–6.

  28. Keller RL, Tacy TA, Hendricks-Munoz K, Xu J, Moon-Grady AJ, Neuhaus J, et al. Congenital diaphragmatic hernia: endothelin-1, pulmonary hypertension, and disease severity. Am J Respir Crit Care Med. 2010;182:555–61.

    Article  CAS  Google Scholar 

  29. Amsallem M, Sternbach JM, Adigopula S, Kobayashi Y, Vu TA, Zamanian R, et al. Addressing the controversy of estimating pulmonary arterial pressure by echocardiography. J Am Soc Echocardiogr. 2016;29:93–102.

    Article  Google Scholar 

  30. Groh GK, Levy PT, Holland MR, Murphy JJ, Sekarski TJ, Myers CL, et al. Doppler echocardiography inaccurately estimates right ventricular pressure in children with elevated right heart pressure. J Am Soc Echocardiogr. 2014;27:163–71.

    Article  Google Scholar 

  31. Musewe NN, Smallhorn JF, Benson LN, Burrows PE, Freedom RM. Validation of Doppler-derived pulmonary arterial pressure in patients with ductus arteriosus under different hemodynamic states. Circulation. 1987;76:1081–91.

    Article  CAS  Google Scholar 

  32. King ME, Braun H, Goldblatt A, Liberthson R, Weyman AE. Interventricular septal configuration as a predictor of right ventricular systolic hypertension in children: a cross-sectional echocardiographic study. Circulation. 1983;68:68–75.

    Article  CAS  Google Scholar 

  33. Ryan T, Petrovic O, Dillon JC, Feigenbaum H, Conley MJ, Armstrong WF. An echocardiographic index for separation of right ventricular volume and pressure overload. J. Am. Coll. Cardiol. 1985;5:918–27.

  34. Averin K, Michelfelder E, Sticka J, Cash M, Hirsch R. Changes in ventricular geometry predict severity of right ventricular hypertension. Pediatr Cardiol. Springer US. 2016;37:575–81.

    Article  Google Scholar 

  35. Levy PT, Patel MD, Groh G, Choudhry S, Murphy J, Holland MR, et al. Pulmonary artery acceleration time provides a reliable estimate of invasive pulmonary hemodynamics in children. J Am Soc Echocardiogr. 2016;29:1056–65.

    Article  Google Scholar 

  36. Dabestani A, Mahan G, Gardin JM, Takenaka K, Allfie A, Henry WL, et al. Evaluation of pulmonary artery pressure and resistance by pulsed Doppler echocardiography. Am J Cardiol. 1987;59:662–8.

    Article  CAS  Google Scholar 

  37. Serwer GA, Cougle AG, Eckerd JM, Armstrong BE. Factors affecting use of the Doppler-determined time from flow onset to maximal pulmonary artery velocity for measurement of pulmonary artery pressure in children. Am J Cardiol. 1986;58:352–6.

    Article  CAS  Google Scholar 

  38. Skinner JR, Boys RJ, A H, Hey EN, Hunter S. Estimation of pulmonary arterial pressure in the newborn: study of the repeatability of four Doppler echocardiographic techniques. Pediatr Cardiol. 1996;17:360–9.

    Article  CAS  Google Scholar 

  39. Koestenberger M, Grangl G, Avian A, Gamillscheg A, Grillitsch M, Cvirn G, et al. Normal reference values and z scores of the pulmonary artery acceleration time in children and its importance for the assessment of pulmonary hypertension. Circ Cardiovasc Imaging. 2017;10. https://doi.org/10.1161/CIRCIMAGING.116.005336.

  40. • Kipfmueller F, Heindel K, Schroeder L, Berg C, Dewald O, Reutter H, et al. Early postnatal echocardiographic assessment of pulmonary blood flow in newborns with congenital diaphragmatic hernia. J Perinat Med. 2018;46:735–43 This study demonstrates the association between the pulmonary artery flow pattern within the first 6 h of life in neonates with CDH and clinical outcomes.

    Article  CAS  Google Scholar 

  41. Desk R, Williams L. Continuous-wave Doppler echocardiographic detection of pulmonary regurgitation and its application to noninvasive estimation of pulmonary. Circulation. 2006;74:484–92.

    Google Scholar 

  42. Sokol J, Bohn D, Lacro RV, Ryan G, Stephens D, Rabinovitch M, et al. Fetal pulmonary artery diameters and their association with lung hypoplasia and postnatal outcome in congenital diaphragmatic hernia. Am J Obstet Gynecol. 2002;186:1085–90.

    Article  Google Scholar 

  43. Okazaki T, Okawada M, Shiyanagi S, Shoji H, Shimizu T, Tanaka T, et al. Significance of pulmonary artery size and blood flow as a predictor of outcome in congenital diaphragmatic hernia. Pediatr Surg Int. 2008;24:1369–73.

    Article  Google Scholar 

  44. Tine F, Wim D, Marc G, Herbert D, Anne D. Congenital diaphragmatic hernia and pulmonary vein obstruction. J Palliat Care Pediatr. 2016;1:13–7.

    Google Scholar 

  45. Lai WW, Gauvreau K, Rivera ES, Saleeb S, Powell AJ, Geva T. Accuracy of guideline recommendations for two-dimensional quantification of the right ventricle by echocardiography. Int J Cardiovasc Imaging. 2008;24:691–8.

    Article  Google Scholar 

  46. 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;23:465–7.

    Article  Google Scholar 

  47. Vogel M, McElhinney DB, Marcus E, Morash D, Jennings RW, Tworetzky W. Significance and outcome of left heart hypoplasia in fetal congenital diaphragmatic hernia. Ultrasound Obstet Gynecol. 2010;35:310–7.

    Article  CAS  Google Scholar 

  48. Levy PT, Dioneda B, Holland MR, Sekarski TJ, Lee CK, Mathur A, et al. Right ventricular function in preterm and term neonates: reference values for right ventricle areas and fractional area of change. J Am Soc Echocardiogr. 2015;28:559–69.

    Article  Google Scholar 

  49. Jain A, Mohamed A, El-Khuffash A, Connelly KA, Dallaire F, Jankov RP, et al. A comprehensive echocardiographic protocol for assessing neonatal right ventricular dimensions and function in the transitional period: normative data and z scores. J Am Soc Echocardiogr. 2014;27:1293–304.

    Article  Google Scholar 

  50. Miller D, Farah MG, Liner A, Fox K, Schluchter M, Hoit BD. The relation between quantitative right ventricular ejection fraction and indices of tricuspid annular motion and myocardial performance. J Am Soc Echocardiogr. 2004;17:443–7.

    Article  Google Scholar 

  51. Koestenberger M, Ravekes W, Everett AD, Stueger HP, Heinzl B, Gamillscheg A, et al. Right ventricular function in infants, children and adolescents: reference values of the tricuspid annular plane systolic excursion (TAPSE) in 640 healthy patients and calculation of z score values. J Am Soc Echocardiogr. 2009;22:715–9.

    Article  Google Scholar 

  52. Eidem BW, Tei C, O’Leary PW, Cetta F, Seward JB. Nongeometric quantitative assessment of right and left ventricular function: myocardial performance index in normal children and patients with Ebstein anomaly. J Am Soc Echocardiogr. 1998;11:849–56.

    Article  CAS  Google Scholar 

  53. Tei C, Ling L, Hodge D, Bailey K, Oh J, Rodeheffer R, et al. New index of combined systolic and diastolic myocardial performance: a simple and reproducible measure of cardiac function—a study in normals and dilated cardiomyopathy. J Cardiol. 1995;2:357–66.

    Google Scholar 

  54. Mertens LL, Friedberg MK. Systolic ventricular function. In: Lai WW, Mertens LL, Cohen MS, Geva T, editors. Echocardiography in pediatric congenital heart disease: from fetus to adult. Second Edi ed. Oxford: Wiley-Blackwell; 2016. p. 96–131.

    Chapter  Google Scholar 

  55. Alp H, Karaarslan S, Baysal T, Çimen D, Örs R, Oran B. Normal values of left and right ventricular function measured by M-mode, pulsed Doppler and Doppler tissue imaging in healthy term neonates during a 1-year period. Early Hum Dev. Elsevier Ltd. 2012;88:853–9.

    Article  Google Scholar 

  56. Roberson DA, Cui W. Right ventricular Tei index in children: effect of method, age, body surface area, and heart rate. J Am Soc Echocardiogr. 2007;20:764–70.

    Article  Google Scholar 

  57. Cui W, Roberson DA. Left ventricular Tei index in children: comparison of tissue Doppler imaging, pulsed wave Doppler, and M-mode echocardiography normal values. J Am Soc Echocardiogr. 2006;19:1438–45.

    Article  Google Scholar 

  58. Yeo TC, Dujardin KS, Tei C, Mahoney DW, McGoon MD, Seward JB. Value of a Doppler-derived index combining systolic and diastolic time intervals in predicting outcome in primary pulmonary hypertension. Am J Cardiol. 1998;81:1157–61.

    Article  CAS  Google Scholar 

  59. Sernich S, Carrasquero N, Lavie CJ, Chambers R, McGettigan M. Noninvasive assessment of the right and left ventricular function in neonates with congenital diaphragmatic hernia with persistent pulmonary hypertension before and after surgical repair. Ochsner J. 2006;6:48–53.

    PubMed  PubMed Central  Google Scholar 

  60. Sanchez AA, Levy PT, Sekarski TJ, Hamvas A, Holland MR, Singh GK. Effects of frame rate on two-dimensional speckle tracking-derived measurements of myocardial deformation in premature infants. Echocardiography. 2015;32:839–47.

    Article  Google Scholar 

  61. Voigt J-U, Pedrizzetti G, Lysyansky P, Marwick TH, Houle H, Baumann R, et al. Definitions for a common standard for 2D speckle tracking echocardiography: consensus document of the EACVI/ASE/Industry Task Force to standardize deformation imaging. J Am Soc Echocardiogr Am Soc Echocardiogr. 2015;28:183–93.

    Article  Google Scholar 

  62. Weidemann F, Jamal F, Sutherland GR, Claus P, Kowalski M, Hatle L, et al. Myocardial function defined by strain rate and strain during alterations in inotropic states and heart rate. Am J Physiol Hear Circ Physiol. 2002;283:H792–9.

    Article  CAS  Google Scholar 

  63. Levy PT, Machefsky A, Sanchez AA, Patel MD, Rogal S, Fowler S, et al. Reference ranges of left ventricular strain measures by two-dimensional speckle-tracking echocardiography in children: a systematic review and meta-analysis. J Am Soc Echocardiogr. 2016;29:209–25.

    Article  Google Scholar 

  64. Levy PT, Sanchez Mejia AA, Machefsky A, Fowler S, Holland MR, Singh GK. Normal ranges of right ventricular systolic and diastolic strain measures in children: a systematic review and meta-analysis. J Am Soc Echocardiogr. 2014;27:549–560.e3.

    PubMed Central  Google Scholar 

  65. Jurcut R, Giusca S, Ticulescu R, Popa E, Amzulescu MS, Ghiorghiu I, et al. Different patterns of adaptation of the right ventricle to pressure overload: a comparison between pulmonary hypertension and pulmonary stenosis. J Am Soc Echocardiogr. 2011;24:1109–17.

    Article  Google Scholar 

  66. Sachdev A, Villarraga HR, Frantz RP, McGoon MD, Hsiao JF, Maalouf JF, et al. Right ventricular strain for prediction of survival in patients with pulmonary arterial hypertension. Chest. 2011;139:1299–309.

    Article  Google Scholar 

  67. Hiraishi S, Agata Y, Saito K, Oguchi K, Misawa H, Fujino N, et al. Interatrial shunt flow profiles in newborn infants: a colour flow and pulsed Doppler echocardiographic study. Br Heart J. 1991;65:41–5.

    Article  CAS  Google Scholar 

  68. •• Morini F, Valfrè L, Bagolan P. Long-term morbidity of congenital diaphragmatic hernia: a plea for standardization. Semin Pediatr Surg. 2017;26:301–10. This study examines the long-term morbidities in CDH patients and variability of follow-up in various PH centers.

    Article  Google Scholar 

  69. •• Kraemer US, Leeuwen L, Krasemann TB, Wijnen RMH, Tibboel D, IJsselstijn H. Characteristics of infants with congenital diaphragmatic hernia who need follow-up of pulmonary hypertension. Pediatr Crit Care Med. 2018;19:e219–e226. The first prospective study that assessed the need for routine evaluation of PH in CDH patients with or without PH at hospital discharge.

  70. •• Hollinger LE, Harting MT, Lally KP. Long-term follow-up of congenital diaphragmatic hernia. Semin Pediatr Surg. 2017;26:178–84 A review of long-term morbidity seen in CDH survivors which proposes a schedule for long-term multidisciplinary follow-up.

    Article  Google Scholar 

  71. Tracy S, Chen C. Multidisciplinary long-term follow-up of congenital diaphragmatic hernia: a growing trend. Semin Fetal Neonatal Med. 2014;19:385–91.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatrics, University of Minnesota, 2450 Riverside Ave, East Building, 5th Floor, Minneapolis, MN, 55454, USA

    Aura A. Sanchez Mejia MD & Nathan J. Rodgers MD, MHA

Authors
  1. Aura A. Sanchez Mejia MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nathan J. Rodgers MD, MHA
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Aura A. Sanchez Mejia MD.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher’s Note

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

This article is part of the Topical Collection on Pediatric and Congenital Heart Disease

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sanchez Mejia, A.A., Rodgers, N.J. Evaluation and Monitoring of Pulmonary Hypertension in Neonates With Congenital Diaphragmatic Hernia. Curr Treat Options Cardio Med 21, 11 (2019). https://doi.org/10.1007/s11936-019-0711-x

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11936-019-0711-x

Keywords

Search

Navigation