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.

  • Comment
  • Published:

Congenital diaphragmatic hernia: exploring the intersection of personal experience and research

Pediatric Research volume 95, pages 883–884 (2024)Cite this article

Congenital diaphragmatic hernia (CDH) is a birth defect due to the antenatal incomplete closure of the diaphragm and herniation of abdominal organs into the chest.1 This inevitably results in a triad of cardiopulmonary anomalies characterized by impaired development of the lung (pulmonary hypoplasia) and its vessels (vascular remodeling predisposing to postnatal pulmonary hypertension), as well as the heart (leading to cardiac dysfunction).1 Abnormal lung development is the principal cause of mortality and morbidity. At birth, most neonates with CDH cannot breathe independently and require mechanical ventilation, some have such severe pulmonary hypoplasia that they need extracorporeal life support, and 70% of infants with CDH develop severe pulmonary hypertension.1 While the general mortality rate is reported as 20–30%, this refers to figures from specialized centers and does not take into account the so-called hidden mortality, owing to terminations of pregnancy or intra-uterine fetal demises.2,3,4 A national study from Sweden reported a hidden mortality of 45%.4 Also, the figures for the mortality rate from low- and middle-income countries are between 40 and 100%, definitely far worse than what could be expected in the twenty-first century. Among the babies that survive, 60% have lung-related sequelae that persist throughout their lives, and about 25% have various neurodevelopmental challenges.1 The severity of these health issues directly correlates with the degree of pulmonary hypoplasia.1 Studies from the USA reported that CDH has the highest median cost of all pediatric surgical conditions (>US$390 million/year spent on CDH patients).1 Thus, pulmonary hypoplasia secondary to CDH imposes a tremendous burden on the affected child, family, and society.

Mr. Evans’ letter highlights very well several challenges that babies with CDH and their families face along the journey.5 In our opinion, the worst of all is the lack of awareness. Although rare, CDH is more common than spina bifida and cystic fibrosis. Yet, CDH receives comparatively far less public awareness and research funding than the other two conditions. Unfortunately, in some instances, the unawareness of the general public is also found in healthcare providers that ignore the existence or the complexity of the condition. Great support to families and healthcare workers has come from the work of family associations, such as CDH International and CDH UK. These and other associations have been providing support for families of patients with CDH, raising awareness throughout the general public, and promoting research initiatives in the field.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

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

References

  1. Zani, A. et al. Congenital diaphragmatic hernia. Nat. Rev. Dis. Prim. 8, 37 (2022).

    Article  PubMed  Google Scholar 

  2. Puri, P. & Gorman, F. Lethal nonpulmonary anomalies associated with congenital diaphragmatic hernia: implications for early intrauterine surgery. J. Pediatr. Surg. 19, 29–32 (1984).

    Article  CAS  PubMed  Google Scholar 

  3. Sweed, Y. & Puri, P. Congenital diaphragmatic hernia: influence of associated malformations on survival. Arch. Dis. Child. 69, 68–70 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Burgos, C. M. & Frenckner, B. Addressing the hidden mortality in CDH: a population-based study. J. Pediatr. Surg. 52, 522–525 (2017).

    Article  PubMed  Google Scholar 

  5. Evans, B. Family reflections: CDH-three letters that forever changed my life. Pediatr. Res. https://doi.org/10.1038/s41390-023-02484-7 (2023).

  6. Deprest, J. A. et al. Randomized trial of fetal surgery for severe left diaphragmatic hernia. N. Engl. J. Med. 385, 107–118 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  7. Russo, F. et al. Antenatal management of congenital diaphragmatic hernia: what’s next? Prenat. Diagn. 42, 291–300 (2022).

    Article  PubMed  Google Scholar 

  8. Russo, F. M. et al. Current and future antenatal management of isolated congenital diaphragmatic hernia. Semin. Fetal Neonatal Med. 22, 383–390 (2017).

    Article  PubMed  Google Scholar 

  9. Perrone, E. E. & Deprest, J. A. Fetal endoscopic tracheal occlusion for congenital diaphragmatic hernia: a narrative review of the history, current practice, and future directions. Transl. Pediatr. 10, 1448–1460 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  10. Deprest, J. et al. Prenatal management of the fetus with isolated congenital diaphragmatic hernia in the era of the TOTAL trial. Semin. Fetal Neonatal Med. 19, 338–348 (2014).

    Article  PubMed  Google Scholar 

  11. Toso, A, et al. Congenital diaphragmatic hernia: phosphodiesterase-5 and arginase inhibitors prevent pulmonary vascular hypoplasia in rat lungs. Pediatr. Res. (In press).

  12. Grasemann, H. Arginase inhibition prevents bleomycin-induced pulmonary hypertension, vascular remodeling, and collagen deposition in neonatal rat lungs. Am. J. Physiol. Lung Cell Mol. Physiol. 308, L503–L510 (2015).

    Article  CAS  PubMed  Google Scholar 

  13. Pels, A. et al. Maternal sildenafil vs placebo in pregnant women with severe early-onset fetal growth restriction: a randomized clinical trial. JAMA Netw. Open. 3, e205323 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  14. De Bie, F. R. et al. Prenatal treprostinil reduces the pulmonary hypertension phenotype in the rat model of congenital diaphragmatic hernia. EBioMedicine 81, 104106 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  15. Antounians, L. et al. Fetal lung underdevelopment is rescued by administration of amniotic fluid stem cell extracellular vesicles in rodents. Sci. Transl. Med. 13, eaax5941 (2021).

    Article  CAS  PubMed  Google Scholar 

  16. Yáñez-Mó, M. et al. Biological properties of extracellular vesicles and their physiological functions. J. Extracell. Vesicles. 4, 27066 (2015).

    Article  PubMed  Google Scholar 

  17. Power, B. et al. Long-term feeding issue and its impact on the daily life of congenitaldiaphragmatic hernia survivors: results of the first patient-led survey. Pediatr. Surg. Int. 36, 63 (2020).

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Developmental and Stem Cell Biology Program, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto, M5G 0A4, ON, Canada

    Augusto Zani

  2. Division of General and Thoracic Surgery, The Hospital for Sick Children, Toronto, M5G 1X8, ON, Canada

    Augusto Zani

  3. Department of Surgery, University of Toronto, Toronto, M5T 1P5, ON, Canada

    Augusto Zani

  4. Beacon Hospital, University College Dublin, Dublin, Ireland

    Prem Puri

  5. Conway Institute of Biomolecular and Biomedical Research, School of Medicine, University College Dublin, Dublin, Ireland

    Prem Puri

Authors
  1. Augusto Zani
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Prem Puri
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

A.Z. and P.P. contributed to the conception, design, and drafting of the commentary. Both A.Z. and P.P. approved the final version of the manuscript.

Corresponding author

Correspondence to Augusto Zani.

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.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zani, A., Puri, P. Congenital diaphragmatic hernia: exploring the intersection of personal experience and research. Pediatr Res 95, 883–884 (2024). https://doi.org/10.1038/s41390-023-02664-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41390-023-02664-5

This article is cited by

Search

Advanced search

Quick links