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Congenital diaphragmatic hernia

Nature Reviews Disease Primers volume 8, Article number: 37 (2022) Cite this article

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Abstract

Congenital diaphragmatic hernia (CDH) is a rare birth defect characterized by incomplete closure of the diaphragm and herniation of fetal abdominal organs into the chest that results in pulmonary hypoplasia, postnatal pulmonary hypertension owing to vascular remodelling and cardiac dysfunction. The high mortality and morbidity rates associated with CDH are directly related to the severity of cardiopulmonary pathophysiology. Although the aetiology remains unknown, CDH has a polygenic origin in approximately one-third of cases. CDH is typically diagnosed with antenatal ultrasonography, which also aids in risk stratification, alongside fetal MRI and echocardiography. At specialized centres, prenatal management includes fetal endoscopic tracheal occlusion, which is a surgical intervention aimed at promoting lung growth in utero. Postnatal management focuses on cardiopulmonary stabilization and, in severe cases, can involve extracorporeal life support. Clinical practice guidelines continue to evolve owing to the rapidly changing landscape of therapeutic options, which include pulmonary hypertension management, ventilation strategies and surgical approaches. Survivors often have long-term, multisystem morbidities, including pulmonary dysfunction, gastroesophageal reflux, musculoskeletal deformities and neurodevelopmental impairment. Emerging research focuses on small RNA species as biomarkers of severity and regenerative medicine approaches to improve fetal lung development.

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Fig. 1: Diagram of a left Bochdalek CDH, showing liver up and mediastinal shift to the right along with cardiopulmonary compression.
Fig. 2: Schematic drawings and ultrasonography images of relevant sections for calculation of the observed/expected lung-to-head ratio.
Fig. 3: Congenital Diaphragmatic Hernia Study Group defect size diagram, drawn with the diaphragm (defect) on the patient’s left looking up from the abdomen towards the chest.
Fig. 4: Schematic representation of FETO procedure.
Fig. 5: Pathophysiological mechanisms, postnatal phenotypes and management strategies in CDH12,65,66,158,177,178,179,182,193,194,197,201.
Fig. 6: Long-term quality of life, comorbidities and interventions in patients with CDH.

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Acknowledgements

A.Z. is supported by the Canadian Institutes of Health Research project grant 175300 and SickKids Foundation R00DH00000. W.K.C. is supported by grant NICHD P01 HD068250. J.D. has been supported by WT101957 from the Wellcome Trust and NS/A/000027/1 from the Engineering and Physical Sciences Research Council of the UK, and by the Great Ormond Street Hospital and University College London Hospital Charities. R.K. is supported by project grants (148797, 178347 and 178387) from the Canadian Institutes of Health Research and is the inaugural Thorlakson Chair of Surgical Research for the University of Manitoba.

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Authors and Affiliations

  1. Division of General and Thoracic Surgery, The Hospital for Sick Children, Department of Surgery, University of Toronto, Toronto, Ontario, Canada

    Augusto Zani & Lina Antounians

  2. Developmental and Stem Cell Biology Program, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto, Ontario, Canada

    Augusto Zani & Lina Antounians

  3. Department of Paediatrics, Columbia University, New York, NY, USA

    Wendy K. Chung

  4. Department of Development and Regeneration, Cluster Woman and Child and Clinical Department of Obstetrics and Gynaecology, University Hospitals, KU Leuven, Leuven, Belgium

    Jan Deprest

  5. Institute for Women’s Health, UCL, London, UK

    Jan Deprest

  6. Department of Paediatric Surgery, McGovern Medical School at the University of Texas Health Science Center, Houston, TX, USA

    Matthew T. Harting

  7. The Comprehensive Center for CDH Care, Children’s Memorial Hermann Hospital, Houston, TX, USA

    Matthew T. Harting

  8. Division of Pediatric Surgery, Le Bonheur Children’s Hospital, University of Tennessee Health Science Center, Memphis, TN, USA

    Tim Jancelewicz

  9. Division of General Paediatric Surgery, Johns Hopkins Children’s Center, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Shaun M. Kunisaki

  10. Department of Neonatology, Royal Hospital for Children, Glasgow, UK

    Neil Patel

  11. Department of Paediatric Surgery, Harvey E. Beardmore Division of Paediatric Surgery, Montreal Children’s Hospital of the McGill University Health Centre, Montreal, Quebec, Canada

    Pramod S. Puligandla

  12. Department of Surgery, Division of Paediatric Surgery, Paediatrics & Child Health, Physiology & Pathophysiology, University of Manitoba, Winnipeg, Manitoba, Canada

    Richard Keijzer

  13. Children’s Hospital Research Institute of Manitoba, Winnipeg, Manitoba, Canada

    Richard Keijzer

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  1. Augusto Zani
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  2. Wendy K. Chung
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Contributions

Introduction (A.Z., P.S.P. and R.K.); Epidemiology (A.Z. and M.T.H.); Mechanisms/pathophysiology (W.K.C., S.M.K., L.A., P.S.P. and R.K.); Diagnosis, screening and prevention (J.D., T.J., S.M.K., N.P. and L.A.); Management (J.D., M.T.H., T.J., N.P. and P.S.P.); Quality of life (L.A., P.S.P., A.Z. and M.T.H.); Outlook (A.Z., S.M.K. and R.K.).

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Correspondence to Augusto Zani.

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Nature Reviews Disease Primers thanks Hiroomi Okuyama, Oluyinka Olurotimi Olutoye, Prem Puri, Thomas F. Schaible and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Zani, A., Chung, W.K., Deprest, J. et al. Congenital diaphragmatic hernia. Nat Rev Dis Primers 8, 37 (2022). https://doi.org/10.1038/s41572-022-00362-w

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