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  • Clinical Research Article
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Perfused boundary region as biomarker for endothelial integrity in former preterms in adolescence

Pediatric Research volume 93, pages 1936–1942 (2023)Cite this article

Abstract

Introduction

Extremely low birth weight (ELBW) survivors have microvascular structural differences already described in kidney and retina, suggesting changes in endothelial integrity. A biomarker of endothelial integrity is perfused boundary region (PBR), which measures glycocalycal thickness. The endothelial glycocalyx is a complex, highly versatile structure with essential roles in vascular integrity and function. We explored PBR patterns together with other microvascular markers in healthy controls and former ELBW children.

Methods

In the PREMATCH cohort (87 healthy controls, 93 ELBW survivors), we assessed endothelial integrity by calculating PBR (sidestream dark-field imaging), several microvascular markers (blood pressure, estimated glomerular filtration rate (eGFRcysC)), and retinal imaging in early adolescence. We explored differences between both groups, and searched for perinatal determinants of PBR and correlations between different microvascular markers.

Results

We provided reference values for PBR (average 1.90 µm, SD 0.30) in children. PBR was not different from ELBW survivors during early adolescence, despite their higher blood pressure, lower eGFRcysC, and different retinal vessel width and tortuosity.

Conclusions

We generated reference values for PBR in early adolescence. Despite some correlations between microvascular parameters, there seem to be numerous confounders to propose PBR as a marker for endothelial integrity in ELBW survivors.

Impact

  • The endothelial glycocalyx is a complex and versatile structure. Changes in blood pressure and retinal and renal vascularization suggest a disturbance of its integrity in extremely low birth weight (ELBW) survivors. Its thickness can be measured by calculating perfused boundary region (PBR) using sidestream dark-field imaging, with a higher PBR indicating a thinner glycocalyx.

  • We generated reference values for PBR in healthy adolescents. These values were not different in former ELBW children.

  • Despite some correlations of PBR with other microvascular biomarkers, these are not strong enough to describe endothelial integrity and its covariates in former ELBW children.

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Fig. 1: Study design.
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Data availability

The corresponding author can be contacted to share the raw data, if based on a reasonable request and study protocol.

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Acknowledgements

We gratefully acknowledge the contribution of the nurses working at the examination center (Linda Custers, Marie-Jeanne Jehoul, Daisy Thijs, and Hanne Truyens) and the clerical staff at the Studies Coordinating Centre at the time of data acquisition (Vera De Leebeeck and Renilde Wolfs).

Funding

The PREMATCH study was supported by the Agency for Innovation by Science and Technology in Flanders (IWT) through the SAFE-PEDRUG project [IWT/SBO 130033]. KU Leuven Internal Funds (STG-18–00379) supported the Research Unit Hypertension and Cardiovascular Epidemiology, Department of Cardiovascular Sciences, Leuven.

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Author notes

  1. These authors contributed equally: Liselotte Van Loo, Karel Allegaert.

Authors and Affiliations

  1. Department of Development and Regeneration, KU Leuven, Leuven, Belgium

    Liselotte Van Loo, Karel Allegaert, Elena Levtchenko & Anke Raaijmakers

  2. Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium

    Liselotte Van Loo, Karel Allegaert & Anke Raaijmakers

  3. Department of Hospital Pharmacy, Erasmus MC, Rotterdam, The Netherlands

    Karel Allegaert

  4. Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven, Leuven, Belgium

    Zhenyu Zhang

  5. Non-Profit Research Institute Alliance for the Promotion of Preventive Medicine, Mechelen, Belgium

    Jan A. Staessen

  6. Biomedical Research Group, Faculty of Medicine, KU Leuven, Leuven, Belgium

    Jan A. Staessen

  7. Department of Pediatrics, ZNA Hospitals Antwerp, Antwerp, Belgium

    Anke Raaijmakers

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Contributions

K.A., E.L., J.A.S., and A.R. conceived and designed the PREMATCH study and obtained the funding. The data on perfused boundary region were analyzed by L.v.L, assisted by K.A., J.A.S., and A.R. All authors were involved in the interpretation and drafting of the manuscript, approved the final manuscript as submitted, and agree to be accountable for all aspects of the work.

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Correspondence to Karel Allegaert.

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Van Loo, L., Allegaert, K., Levtchenko, E. et al. Perfused boundary region as biomarker for endothelial integrity in former preterms in adolescence. Pediatr Res 93, 1936–1942 (2023). https://doi.org/10.1038/s41390-022-02321-3

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