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Very preterm birth results in later lower platelet activation markers

Pediatric Research volume 89, pages 1278–1282 (2021)Cite this article

Abstract

Background

Premature birth entails an adverse cardiovascular risk profile, but the underlying mechanisms are insufficiently understood. Here, we employed an unbiased cardiovascular proteomics approach to profile former very preterm-born preschoolers.

Methods

This observational study investigated differences in plasma concentrations of 79 proteins, including putative cardiovascular biomarkers between very preterm- and term-born children on average 5.5 years old (53.1% male) using multiple-reaction monitoring mass spectrometry.

Results

Very preterm-born (n = 38; median gestational age 29.6 weeks) compared to term-born (n = 26; 40.2 weeks) children featured lower plasma concentrations of platelet factor 4 (PLF4; −61.6%, P < 0.0001), platelet basic protein (CXCL7; −57.8%, P < 0.0001), and hemoglobin subunit beta (−48.3%, P < 0.0001). Results remained virtually unchanged when adjusting for complete blood count parameters, including platelet count. Conversely, whole blood hemoglobin was higher (+7.62%, P < 0.0001) in preterm-born children.

Conclusions

Very preterm birth was associated with decreased markers of platelet activation among preschoolers. These findings are consistent with reduced platelet reactivity persisting from very preterm birth to a preschool age.

Impact

  • Former very preterm-born preschoolers featured reduced levels of platelet activation markers.

  • While lower platelet reactivity in very preterm-born compared to term-born infants in the first days of life was established, it was unknown when, if at all, reactivity normalizes. The current study suggests that platelet hyporeactivity due to very preterm birth persists at least up to a preschool age.

  • “Immaturity of the hemostatic system” may be a persistent sequel of preterm birth, but larger studies are needed to investigate its potential clinical implications.

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Fig. 1: Differences in plasma concentrations of 79 proteins between former very preterm-born and former term-born preschoolers under adjustment for age and sex.

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Acknowledgements

This study was supported by the Anniversary Fund of the Austrian National Bank (Project No. 14570) and the Austrian Heart Foundation, and by VASCage—Research Center on Vascular Ageing and Stroke (No. 868624). As a COMET center, VASCage is funded within the COMET program—Competence Centers for Excellent Technologies by the Austrian Ministry for Climate Action, Environment, Energy, Mobility, Innovation, and Technology, the Austrian Ministry for Digital and Economic Affairs, and the federal states Tyrol, Salzburg, and Vienna. Prof. Manuel Mayr is a British Heart Foundation (BHF) Chair Holder (CH/16/3/32406) with BHF program grant support (RG/16/14/32397). This work was supported by the National Institute of Health Research (NIHR) Biomedical Research Center based at Guy’s and St. Thomas’ National Health Service (NHS) Foundation Trust and King’s College London in partnership with King’s College Hospital.

Author information

Affiliations

  1. Department of Neurology, Medical University of Innsbruck, Innsbruck, Tyrol, Austria

    Raimund Pechlaner, Sophia Julia Kiechl & Stefan Kiechl

  2. Department of Pediatrics II, Medical University of Innsbruck, Innsbruck, Tyrol, Austria

    Anna Posod & Ursula Kiechl-Kohlendorfer

  3. King’s British Heart Foundation Centre, King’s College London, London, UK

    Xiaoke Yin, Sean Anthony Burnap & Manuel Mayr

  4. VASCage, Research Centre for Promoting Vascular Health in the Ageing Community, Innsbruck, Tyrol, Austria

    Sophia Julia Kiechl & Stefan Kiechl

Authors
  1. Raimund Pechlaner
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  2. Anna Posod
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  3. Xiaoke Yin
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  4. Sean Anthony Burnap
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  5. Sophia Julia Kiechl
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  6. Manuel Mayr
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  7. Stefan Kiechl
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  8. Ursula Kiechl-Kohlendorfer
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Contributions

Designed the study: U.K.-K. and A.P. Obtained funding: U.K.-K. and S.K. Supervised the study: U.K.-K. Analyzed the data: R.P. Drafted the manuscript: R.P. Revised the manuscript for important intellectual content: A.P., X.Y., S.A.P., S.J.K., M.M., S.K., and U.K.-K. Performed proteomics measurements: X.Y. and S.A.P. Approved the final version of the manuscript submitted: all authors.

Corresponding author

Correspondence to Ursula Kiechl-Kohlendorfer.

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The authors declare no competing interests.

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All children included in this study consented to participation orally, and written informed consent was obtained from their legal guardians.

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Pechlaner, R., Posod, A., Yin, X. et al. Very preterm birth results in later lower platelet activation markers. Pediatr Res 89, 1278–1282 (2021). https://doi.org/10.1038/s41390-020-1070-8

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