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  • Clinical Research Article
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Early nitric oxide is not associated with improved outcomes in congenital diaphragmatic hernia

Pediatric Research volume 93, pages 1899–1906 (2023)Cite this article

A Correction to this article was published on 12 April 2023

This article has been updated

Abstract

Background

Inhaled nitric oxide (iNO) is widely used for the management of infants with congenital diaphragmatic hernia (CDH); however, evidence of benefit is limited.

Methods

This is a multicenter cohort study using data from the Congenital Diaphragmatic Hernia Study Group between 2015 and 2020. The impact of early iNO use in the first 3 days of life prior to ECLS use on mortality or ECLS use was explored using multivariate logistic regression models and subgroup analyses.

Results

Of the 1777 infants, 863 (48.6%) infants received early iNO treatment. Infants receiving iNO had lower birth weight, larger defect size, more severe pulmonary hypertension, and abnormal ventricular size and function. After controlling for these factors, early iNO use was associated with increased mortality (aOR 2.06, 95% CI 1.05–4.03, P = 0.03) and increased ECLS use (aOR 3.44, 95% CI 2.11–5.60, P < 0.001). Subgroup analyses after stratification by echocardiographic characteristics and defect size revealed no subgroup with a reduction in mortality or ECLS use.

Conclusions

Use of iNO in the first 3 days of life prior to ECLS was not associated with a reduction in mortality or ECLS use in either the regression models or the subgroup analyses. The widespread use of iNO in this vulnerable population requires reconsideration.

Impact

  • Evidence to support widespread use of iNO for infants with congenital diaphragmatic hernia is limited.

  • The use of iNO in the first 3 days of life was associated with significantly increased mortality and ECLS use.

  • Stratification by echocardiographic characteristics and defect size did not reveal a subgroup that benefited from iNO. Even the subset of patients with R-to-L shunts at both ductal and atrial levels, a surrogate for elevated pulmonary arterial pressures in the absence of significantly decreased LV compliance, did not benefit from early iNO use.

  • Early iNO therapy was of no benefit in the management of acute pulmonary hypertension in infants with congenital diaphragmatic hernia, supporting reconsideration of its use in this population.

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Fig. 1
Fig. 2: The impact of early iNO therapy on death and ECLS use based on multivariate regression models.

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Data availability

The data that support the findings of this study are available from the CDHSG but membership restrictions apply, therefore the data are not publicly available. Under unique and special circumstances, data could be made available from the authors following reasonable request, for a specific rationale, and with permission of the CDHSG.

Change history

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Acknowledgements

We acknowledge the ongoing contributions of highly committed Congenital Diaphragmatic Hernia Study Group member centers that voluntarily participate in the study of congenital diaphragmatic hernia.

Funding

This study was supported by a grant from the Maternal & Child Health Research Institute at Stanford awarded to C.Y.N. The sponsor had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

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Author notes

  1. A full list of members and their affiliations appears in the Supplementary Information.

Authors and Affiliations

  1. Division of Neonatal and Developmental Medicine, Stanford University School of Medicine and Lucile Packard Children’s Hospital, Palo Alto, CA, USA

    Caroline Y. Noh, Valerie Y. Chock, Shazia Bhombal & Krisa P. Van Meurs

  2. Division of Pediatric Surgery, Weill Cornell Medical College, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Enrico Danzer

  3. Royal Hospital for Children Glasgow, Glasgow, UK

    Neil Patel

  4. Quantitative Sciences Unit, Stanford University School of Medicine, Palo Alto, CA, USA

    Alex Dahlen

  5. Department of Pediatric Surgery, McGovern Medical School at the University of Texas Health Science Center at Houston and Children’s Memorial Hermann Hospital, Houston, TX, USA

    Matthew T. Harting, Kevin P. Lally & Ashley H. Ebanks

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Contributions

C.Y.N., V.Y.C., S.B., and K.P.V.M. made substantial contributions to conception and design of the study; acquisition, analysis, and interpretation of data; and drafting and critical revision of the manuscript. E.D. made substantial contributions to conception and design of the study; acquisition, analysis, and interpretation of data; and critical revision of the manuscript for important intellectual content. N.P., A.D., M.T.H., K.P.L., and A.H.E. made substantial contributions to acquisition, analysis, and interpretation of data and critical revision of the manuscript for important intellectual content. All the authors agreed and approved this version to be submitted for publication.

Corresponding author

Correspondence to Caroline Y. Noh.

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The authors declare no competing interests.

Ethics approval and consent to participate

The CDHSG registry is hosted by the University of Texas at Houston and approved by its Institutional Review Board (HSC-MS-03-223) with waiver of informed consent.

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The original online version of this article was revised: due to a typesetting error, the headings of two separate columns in Table 3 were unfortunately merged into one.

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Noh, C.Y., Chock, V.Y., Bhombal, S. et al. Early nitric oxide is not associated with improved outcomes in congenital diaphragmatic hernia. Pediatr Res 93, 1899–1906 (2023). https://doi.org/10.1038/s41390-023-02491-8

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  • DOI: https://doi.org/10.1038/s41390-023-02491-8

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