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Endostatin and ST2 are predictors of pulmonary hypertension disease course in infants

Journal of Perinatology volume 40, pages 1625–1633 (2020)Cite this article

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A Correction to this article was published on 02 June 2020

This article has been updated

Abstract

Introduction

Pulmonary hypertension (PH) is a common comorbidity of cardiopulmonary disease. Endostatin, an inhibitor of angiogenesis, is elevated in neonates with lung disease. ST2 is a heart failure biomarker correlated with PH in adults. We hypothesized that these biomarkers may be useful in diagnosing PH and categorizing its severity in infants.

Methods

Endostatin, ST2, and NT-proBNP plasma concentrations from 26 infants with PH and 21 control infants without PH were correlated with echocardiographic and clinical features using regression models over time.

Results

Endostatin, ST2, and NT-proBNP concentrations were elevated in PH participants versus controls (p < 0.0001). Endostatin was associated with right ventricular dysfunction (p = 0.014), septal flattening (p = 0.047), and pericardial effusion (p < 0.0001). ST2 concentrations predicted right to left patent ductus arteriosus flow (p = 0.009). NT-proBNP was not associated with PH features.

Conclusions

Endostatin and ST2 concentrations were associated with echocardiographic markers of worse PH in infants and may be better predictors than existing clinical standards.

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Fig. 1: Endostatin, ST2, and NT-ProBNP in pulmonary hypertension versus controls (ng/mL, median and IQR) at enrollment.
Fig. 2: ROC curve of endostatin, ST2, and NT-ProBNP in pulmonary hypertension versus controls.
Fig. 3: Biomarker concentrations in PH subjects by echocardiographic finding (adjusted over multiple visits).

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Funding

MG was supported by the Pediatric Scientist Development Program. The Pediatric Scientist Development Program is supported by Award Number K12-HD000850 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. JMC received support from a Johns Hopkins All Children’s Hospital Foundation Institutional Research Grant. The work was supported in part by a Johns Hopkins All Children’s Foundation Institutional Research Grant (PI: N.A. Goldenberg; Johns Hopkins “iPICS” prospective multi-cohort and biobanking study of pediatric acute and chronic health conditions).

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Authors and Affiliations

  1. Division of Pediatric Cardiology, Department of Pediatrics, Johns Hopkins University, Baltimore, MD, USA

    Megan Griffiths, Jun Yang, Allen D. Everett & Melanie Nies

  2. Biostatistics, Epidemiology and Data management (BEAD) Core, Department of Pediatrics, Johns Hopkins University, Baltimore, MD, USA

    Jacky M. Jennings

  3. Division of Pediatric Cardiology, Department of Pediatrics, Johns Hopkins All Children’s Hospital, St, Petersburg, FL, USA

    Grace Freire

  4. Department of Anesthesia and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA

    Monica Williams

  5. Eudowood Division of Pediatric Respiratory Sciences, Department of Pediatrics, Johns Hopkins University, Baltimore, MD, USA

    Sharon A. McGrath-Morrow & Joseph M. Collaco

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  1. Megan Griffiths
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Contributions

MG, JMC, and ADE planned the project, analyzed the data, and wrote the manuscript; MG and JY performed the experiments and interpreted the results; MG and JMC performed statistical analysis; JY, ADE, MN, MW, JMJ, GF, SMM, and JMC recruited participants and performed research; and all authors reviewed, revised, and approved the manuscript for submission.

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Correspondence to Joseph M. Collaco.

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Griffiths, M., Yang, J., Everett, A.D. et al. Endostatin and ST2 are predictors of pulmonary hypertension disease course in infants. J Perinatol 40, 1625–1633 (2020). https://doi.org/10.1038/s41372-020-0671-8

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