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.

  • Clinical Research Article
  • Published:

Utility of urinary NT-proBNP in congenital diaphragmatic hernia: a prospective pilot study

Pediatric Research volume 97, pages 2305–2311 (2025)Cite this article

Abstract

Background

Echocardiography is the reference standard for diagnosing pulmonary hypertension (PH) and cardiac dysfunction (CD) in congenital diaphragmatic hernia (CDH). The use of an adjunct non-invasive biomarker would be invaluable. Plasma N-terminal brain Natriuretic Peptide (NT-proBNP) has been evaluated as a biomarker in CDH. Our objective was to investigate the utility of urinary NT-proBNP as an adjunct biomarker in CDH.

Methods

Prospective observational study of neonates with CDH. Urinary NT-proBNP and its ratio to urinary creatinine (UNBCR) were analyzed at 24 h of life (HOL). Spearman’s correlation was used to quantify the association between the urinary NT-proBNP with corresponding plasma concentrations. Logistic regression and receiver operating characteristic (ROC) curve analyses were used to examine urinary NT-proBNP and UNBCR’s association with need for ECMO. The Kruskal–Wallis test was used to compare urinary NT-proBNP concentrations with echocardiography parameters of PH and CD.

Results

Urinary NT-proBNP and UNBCR positively correlated with plasma concentrations. Patients with high right ventricular (RV) pressures had higher urinary NT-proBNP concentrations. Both urinary NT-proBNP and UNBCR concentrations increased with worsening left and right ventricular dysfunction on first postnatal echocardiogram.

Conclusion

We report the feasibility of urinary NT-proBNP as a non-invasive biomarker to assess PH and CD in CDH.

Impact statement

  • Non-invasive biomarkers are an important area of research in neonates as they have the potential to decrease the need for blood sampling, which may cause pain, stress, and induce iatrogenic anemia. Use of non-invasive biomarkers could be especially useful in congenital diaphragmatic hernia (CDH) who may need Extra-Corporeal Life Support (ECLS) for their management. We evaluated the potential utility of the urinary NT-proBNP in CDH. Plasma NT-proBNP has been studied in neonates with CDH; however, urinary NT-proBNP has not been explored, making this the first study to examine its potential as a biomarker.

Access through your institution
Buy or subscribe

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

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Patient inclusion process
Fig. 2: Urine and plasma NT-proBNP correlation.
Fig. 3: Urinary NT-proBNP and RV function using RV:LV systolic ratio.
Fig. 4: Urinary NT-proBNP as predictor of RV function, LV function and PH.
Fig. 5: Urinary NT-proBNP as predictor of need for ECMO.

Similar content being viewed by others

Data availability

All data generated or analyzed during this study are included in this manuscript.

References

  1. McGivern, M. R. et al. Epidemiology of congenital diaphragmatic hernia in Europe: a register-based study. Arch. Dis. Child Fetal Neonatal Ed. 100, F137–F144 (2015).

    Article  PubMed  Google Scholar 

  2. Pierro, M. & Thebaud, B. Understanding and treating pulmonary hypertension in congenital diaphragmatic hernia. Semin. Fetal Neonatal Med. 19, 357–363 (2014).

    Article  CAS  PubMed  Google Scholar 

  3. Patel, N. et al. Early postnatal ventricular dysfunction is associated with disease severity in patients with congenital diaphragmatic hernia. J. Pediatr. 203, 400–407 (2018).

    Article  PubMed  Google Scholar 

  4. Ferguson, D. M. et al. Early, postnatal pulmonary hypertension severity predicts inpatient outcomes in congenital diaphragmatic hernia. Neonatology 118, 147–154 (2021).

    Article  PubMed  Google Scholar 

  5. El-Khuffash, A. & Molloy, E. J. Are B-type natriuretic peptide (BNP) and N-terminal-pro-BNP useful in neonates? Arch. Dis. Child.-Fetal Neonatal Ed. 92, F320–F324 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  6. Iliodromiti, Z. et al. Serum and urinary N-terminal pro-brain natriuretic peptides as biomarkers for bronchopulmonary dysplasia of preterm neonates. Front. Pediatr. 8, 588738 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  7. Lammers, A. E., Hislop, A. A. & Haworth, S. G. Prognostic value of B-type natriuretic peptide in children with pulmonary hypertension. Int. J. Cardiol. 135, 21–26 (2009).

    Article  PubMed  Google Scholar 

  8. Reynolds, E. W. Brain-type natriuretic peptide in the diagnosis and management of persistent pulmonary hypertension of the newborn. Pediatrics 114, 1297–1304 (2004).

    Article  PubMed  Google Scholar 

  9. Mine, K. et al. B‐type natriuretic peptide for assessment of haemodynamically significant patent ductus arteriosus in premature infants. Acta Paediatr. 102, e347–e352 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Kurihara, N. et al. Usefulness of measurement of urinary N-terminal pro-brain natriuretic peptide in neonatal period. Pediatr. Int. 53, 10–1111 (2011).

    Article  Google Scholar 

  11. Celik, I. H., Erdeve, O., Demırel, G., Canpolat, F. E. & Dilmen, U. Elevated urinary NT-proBNP after pharmacological closure of patent ductus arteriosus in very low birth weight infants. Early Hum. Dev. 89, 187–189 (2013).

    Article  CAS  PubMed  Google Scholar 

  12. Khan, S. S. et al. Urinary NT-proBNP levels and echocardiographic parameters for patent ductus arteriosus. J. Perinatol. 37, 1319–1324 (2017).

    Article  CAS  PubMed  Google Scholar 

  13. Müller, N. et al. Perioperative urinary NT-ProBNP values and their usefulness as diagnostic and prognostic markers in children with congenital heart disease. Clin. Chim. Acta 518, 28–3219 (2021).

    Article  PubMed  Google Scholar 

  14. Naeem, B. et al. Urinary NT-proBNP as a potential noninvasive biomarker for screening of pulmonary hypertension in preterm infants: a pilot study. J. Perinatol. 40, 628–632 (2020).

    Article  PubMed  Google Scholar 

  15. Baptista, M. J. et al. N-terminal-pro-B type natriuretic peptide as a useful tool to evaluate pulmonary hypertension and cardiac function in CDH infants. Neonatology 94, 22–30 (2008).

    Article  CAS  PubMed  Google Scholar 

  16. Gupta, V. S. et al. Elevated proBNP levels are associated with disease severity, cardiac dysfunction, and mortality in congenital diaphragmatic hernia. J. Pediatr. Surg. 56, 1214–1219 (2021).

    Article  PubMed  Google Scholar 

  17. Heindel, K. et al. Early postnatal changes of circulating N-terminal-pro-B-type natriuretic peptide in neonates with congenital diaphragmatic hernia. Early Hum. Dev. 146, 105049 (2020).

    Article  CAS  PubMed  Google Scholar 

  18. Ruano, R. et al. Fetal lung volume and quantification of liver herniation by magnetic resonance imaging in isolated congenital diaphragmatic hernia. Ultrasound Obstet. Gynecol. 43, 662–669 (2014).

    Article  CAS  PubMed  Google Scholar 

  19. Gokulakrishnan, G. et al. Brain natriuretic peptide and N‐terminal brain natriuretic peptide for the diagnosis of haemodynamically significant patent ductus arteriosus in preterm neonates. Cochrane Database Syst. Rev. 12, CD013129 (2022).

    PubMed  Google Scholar 

  20. Cortés, R. et al. Variability of NT‐proBNP plasma and urine levels in patients with stable heart failure: a 2‐year follow‐up study. Heart 93, 957 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  21. Cortés, R. et al. Diagnostic and prognostic value of urine NT‐proBNP levels in heart failure patients. Eur. J. Heart Fail. 8, 621–627 (2006).

    Article  PubMed  Google Scholar 

  22. Reynen, S. et al. Urinary N‐terminal pro‐brain natriuretic peptide: prognostic value in patients with acute chest pain. ESC Heart Fail. 8, 2293–2305 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  23. Abman, S. H. et al. Pediatric pulmonary hypertension: guidelines from the American Heart Association and American thoracic Society. Circulation 132, 2037–2099 (2015).

    Article  PubMed  Google Scholar 

  24. Christou, E. et al. Urinary NT-proBNP: a useful biomarker for the diagnosis of respiratory distress in the neonatal population. Cureus 15, e39019 (2023).

    PubMed  PubMed Central  Google Scholar 

  25. Patel, N., Massolo, A. C., Kraemer, U. S. & Kipfmueller, F. The heart in congenital diaphragmatic hernia: knowns, unknowns, and future priorities. Front. Pediatr. 10, 890422 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  26. Bo, B. et al. Increased N-terminal Pro-B-Type natriuretic peptide during extracorporeal life support is associated with poor outcome in neonates with congenital diaphragmatic hernia. J. Pediatr. 241, 83–89 (2022).

    Article  CAS  PubMed  Google Scholar 

  27. Elgendy, M. M. et al. Acute kidney injury in infants diagnosed with congenital diaphragmatic hernia. Pediatr. Res. 94, 1083–1088 (2023).

    Article  PubMed  Google Scholar 

  28. Anwar, A., Ruffenach, G., Mahajan, A., Eghbali, M. & Umar, S. Novel biomarkers for pulmonary arterial hypertension. Respir. Res. 17, 1–0 (2016).

    Article  Google Scholar 

  29. Warwick, G., Thomas, P. S. & Yates, D. H. Biomarkers in pulmonary hypertension. Eur. Respir. J. 32, 503–512 (2008).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We acknowledge the time, effort, and dedication of the Newborn Center Nursing staff in helping with timely sample collection and storage of patient samples for this project. This study was funded by the Evie Whitlock Funding for Fellows in Neonatal-Perinatal Medicine at Baylor College of Medicine.

Author information

Authors and Affiliations

  1. Division of Neonatology, Department of Pediatrics, Baylor College of Medicine, Houston, USA

    Srirupa Hari Gopal, Kelly Frances Martinek, Joseph L. Hagan, Sharada H. Gowda, Mohan Pammi & Caraciolo J. Fernandes

  2. Division of Pediatric Cardiology, Department of Pediatrics, Baylor College of Medicine, Houston, USA

    Candice Vacher, Judith Becker & Betul Yilmaz Furtun

  3. Division of Pediatric Pulmonology/Pulmonary Hypertension, Department of Pediatrics, Baylor College of Medicine, Houston, USA

    Nidhy P. Varghese

  4. Department of Pathology, Baylor College of Medicine, Houston, USA

    Sridevi Devaraj

Authors
  1. Srirupa Hari Gopal
    View author publications

    Search author on:PubMed Google Scholar

  2. Kelly Frances Martinek
    View author publications

    Search author on:PubMed Google Scholar

  3. Candice Vacher
    View author publications

    Search author on:PubMed Google Scholar

  4. Judith Becker
    View author publications

    Search author on:PubMed Google Scholar

  5. Nidhy P. Varghese
    View author publications

    Search author on:PubMed Google Scholar

  6. Betul Yilmaz Furtun
    View author publications

    Search author on:PubMed Google Scholar

  7. Joseph L. Hagan
    View author publications

    Search author on:PubMed Google Scholar

  8. Sharada H. Gowda
    View author publications

    Search author on:PubMed Google Scholar

  9. Mohan Pammi
    View author publications

    Search author on:PubMed Google Scholar

  10. Sridevi Devaraj
    View author publications

    Search author on:PubMed Google Scholar

  11. Caraciolo J. Fernandes
    View author publications

    Search author on:PubMed Google Scholar

Contributions

Srirupa Hari Gopal- Conceptualization, methodology, investigation, writing original draft, editing draft, funding acquisition, visualization; Kelly Frances Martinek-Investigation, data curation, review original draft; Judith Becker-Investigation, resources, review original draft; Nidhy Varghese- Resources, review original draft; Betul Yilmaz- Resources, review original draft; Joseph Hagan- Data curation, formal analysis, review original draft; Sharada H. Gowda- Resources, review original draft; Mohan Pammi- Methodology, Resources, review original draft; Sridevi Devaraj- Methodology, Resources, review original draft; Caraciolo J. Fernandes- Conceptualization, methodology, resources, supervision, and review of the final manuscript.

Corresponding author

Correspondence to Srirupa Hari Gopal.

Ethics declarations

Competing interests

The authors declare no competing interests.

Consent for publication

Parental consent was required for this study and obtained following Institutional Review Board guidelines.

Additional information

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

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hari Gopal, S., Martinek, K.F., Vacher, C. et al. Utility of urinary NT-proBNP in congenital diaphragmatic hernia: a prospective pilot study. Pediatr Res 97, 2305–2311 (2025). https://doi.org/10.1038/s41390-024-03600-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41390-024-03600-x

This article is cited by

Search

Advanced search

Quick links