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Pediatric congenital heart disease: inflammatory biomarkers mediate the association between preoperative ZlogNT-proBNP and postoperative prolonged ventilation

Pediatric Research (2026)Cite this article

Abstract

Background

Children with congenital heart disease (CHD) often exhibit elevated preoperative NT-proBNP, linked to prolonged postoperative mechanical ventilation. Age-adjusted ZlogNT-proBNP outperforms raw NT-proBNP in predicting outcomes, but its relationship with ventilation duration and underlying inflammatory pathways remain unclear.

Methods

This retrospective cohort study included 113 CHD children. Preoperative ZlogNT-proBNP were quantified and perioperative cytokines (IL-6, IL-8, IL-10) were measured, as well as postoperative ventilation duration were recorded. Multivariable regression and mediation analyses assessed direct and indirect cytokine-mediated effects on prolonged ventilation.

Results

Among the 113 children, 28 (25%) experienced prolonged mechanical ventilation and had significantly higher preoperative ZlogNT-proBNP compared to those with shorter mechanical ventilation durations. Postoperatively, IL-6, IL-8, and IL-10 levels were significantly elevated in the prolonged mechanical ventilation group. Mediation analysis revealed that IL-6, IL-8, and IL-10 partially mediated the association between ZlogNT-proBNP and prolonged mechanical ventilation, with mediation proportions of 28%, 38%, and 37%, respectively.

Conclusion

Elevated preoperative ZlogNT-proBNP was significantly associated with prolonged mechanical ventilation, partly via cytokine-mediated inflammatory pathways. These findings suggest that targeting inflammatory pathways may help optimize perioperative care and reduce ventilation duration.

Impact

  1. 1.

    Preoperative ZlogNT-proBNP levels and postoperative inflammatory markers (IL-6, IL-8, and IL-10) are significantly associated with prolonged postoperative mechanical ventilation duration.

  2. 2.

    Postoperative inflammatory cytokines (IL-6, IL-8, and IL-10) partially mediate the association between preoperative ZlogNT-proBNP levels and prolonged MV duration.

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Fig. 1: Study flowchart and analytical framework.
Fig. 2: Mediation analysis of inflammatory cytokines in the association between NT-proBNP and prolonged mechanical ventilation (MV).

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Data availability

The datasets generated and analyzed during the current study are not publicly available due to patient privacy and institutional data-sharing policies but are available from the corresponding author upon reasonable request and with permission from Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine.

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Acknowledgements

We thank all the members of the Department of pediatric cardiology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine for supporting us.

Funding

This work was supported by the Fundamental Research Funds for the Central Universities (grant number YG2023QNB13). The funders had no role in study design, data collection, analysis, interpretation, or manuscript preparation.

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Author notes

  1. These authors contributed equally: Jihong Huang, Wenyuan Shang.

Authors and Affiliations

  1. Department of Pediatric Cardiology, Xinhua Hospital, affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Jihong Huang, Wenyuan Shang, Sun Chen & Wenjuan Li

  2. Engineering Research Center of Techniques and Instruments for Diagnosis and Treatment of Congenital Heart Disease, Ministry of Education, Xinhua Hospital, affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Sun Chen

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  1. Jihong Huang
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Contributions

Jihong Huang and Wenyuan Shang were involved in gathering data and formal analysis. Jihong Huang wrote the original draft. Wenjuan Li conceived the study and revised the manuscript. Sun Chen revised the manuscript.

Corresponding author

Correspondence to Wenjuan Li.

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Competing interests

The authors declare no competing interests.

Ethics statement

This study was conducted in accordance with the principles outlined in the Declaration of Helsinki and was approved by the Ethics Committee of Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. Due to the retrospective nature of the study, the requirement for written informed consent was waived. All patient data were anonymized prior to analysis to ensure privacy and confidentiality.

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Huang, J., Shang, W., Chen, S. et al. Pediatric congenital heart disease: inflammatory biomarkers mediate the association between preoperative ZlogNT-proBNP and postoperative prolonged ventilation. Pediatr Res (2026). https://doi.org/10.1038/s41390-025-04725-3

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