Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Study Protocol
  • Published:

Markers of platelet activation foR identification of late onset sEpsis in infaNTs: PARENT study protocol

Pediatric Research volume 95, pages 852–856 (2024)Cite this article

Abstract

Background

Newborns are at high risk of sepsis. At present there is no definitive “rule in” blood test for sepsis at the point of clinical concern. A positive blood culture remains the gold standard test for neonatal sepsis, however laboratory markers that correlate prospectively with culture positive sepsis could aid clinicians in making decisions regarding administration of empiric antibiotic therapies.

Methods

This multi-site, prospective observational study will take place in two neonatal intensive care units (National Maternity Hospital and Rotunda Hospital, Dublin). Neonates born at less than 34 weeks will be enroled and informed consent obtained prior to late onset sepsis work up. If at any point subsequently during their neonatal intensive care stay they develop signs and symptoms of possible sepsis requiring blood culture, an additional sodium citrate sample will be obtained. Infants will be categorised into three groups as follows: (i) culture positive sepsis, (ii) culture negative sepsis where an infant receives 5 days of antibiotics (iii) non sepsis. Our primary outcome is to establish if differential platelet/endothelial activation can prospectively identify neonatal culture positive late onset sepsis.

Trial registration number

NCT05530330

Impact

  • Preterm infants are a high risk group for the development of sepsis which is a major cause of mortality in this population.

  • Platelets have been associated with host response to invasive bacterial infections both in animal models and translational work.

  • A positive blood culture is the gold standard test for neonatal sepsis but can be unreliable due to limited blood sampling in the very low birth weight population.

  • This study hopes to establish if platelet/endothelial associated plasma proteins can prospectively identify late onset neonatal sepsis.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1

Similar content being viewed by others

Data availability

Nil data generated to date. On completion of the study, anonymised data available on request and within the limitations of General Data Protection Regulation (GDPR) useage.

References

  1. Fleischmann-Struzek, C. et al. The global burden of paediatric and neonatal sepsis: A systematic review. Lancet Respir. Med 6, 223–230 (2018).

    Article  PubMed  Google Scholar 

  2. Mitre, E. et al. Association between use of acid-suppressive medications and antibiotics during infancy and allergic diseases in early childhood. JAMA Pediatrics 172, e180315–e180315 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  3. Nogacka, A. M. et al. Early microbiota, antibiotics and health. Cell Mol. Life Sci. 75, 83–91 (2018).

    Article  CAS  PubMed  Google Scholar 

  4. Eck, A. et al. Neonatal microbiota development and the effect of early life antibiotics are determined by two distinct settler types. PLOS ONE 15, e0228133 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Esmaeilizand, R. et al. Antibiotic exposure and development of necrotizing enterocolitis in very preterm neonates. Paediatr. Child Health 23, e56–e61 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  6. Patel, S. J. & Saiman, L. Antibiotic resistance in neonatal intensive care unit pathogens: Mechanisms, clinical impact, and prevention including antibiotic stewardship. Clin. Perinatol. 37, 547–563 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  7. Schlapbach, L. J. & Kissoon, N. Defining pediatric sepsis. JAMA Pediatr. 172, 313–314 (2018).

    Article  Google Scholar 

  8. Qazi, S. A. & Stoll, B. J. Neonatal sepsis: A major global public health challenge. Pediatr. Infect. Dis. J. 28, S1–S2 (2009).

    Article  PubMed  Google Scholar 

  9. Alshaikh, B., Yusuf, K. & Sauve, R. Neurodevelopmental outcomes of very low birth weight infants with neonatal sepsis: Systematic review and meta-analysis. J. Perinatol. 33, 558–564 (2013).

    Article  CAS  PubMed  Google Scholar 

  10. Singer, M. et al. The third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA 315, 801–810 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Aziz, K. B. et al. Maximum vasoactive-inotropic score and mortality in extremely premature, extremely low birth weight infants. J. Perinatol. 41, 2337–2344 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Wynn, J. L. & Polin, R. A. A neonatal sequential organ failure assessment score predicts mortality to late-onset sepsis in preterm very low birth weight infants. Pediatr. Res 88, 85–90 (2020).

    Article  PubMed  Google Scholar 

  13. Vazzalwar, R., Pina-Rodrigues, E., Puppala, B. L., Angst, D. B. & Schweig, L. Procalcitonin as a screening test for late-onset sepsis in preterm very low birth weight infants. J. Perinatol. 25, 397–402 (2005).

    Article  CAS  PubMed  Google Scholar 

  14. Guida, J. D., Kunig, A. M., Leef, K. H., McKenzie, S. E. & Paul, D. A. Platelet count and sepsis in very low birth weight neonates: Is there an organism-specific response? Pediatrics 111, 1411–1415 (2003).

    Article  PubMed  Google Scholar 

  15. Sola-Visner, M., Sallmon, H. & Brown, R. New insights into the mechanisms of nonimmune thrombocytopenia in neonates. Semin Perinatol. 33, 43–51 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  16. McDonald, B. et al. Platelets and neutrophil extracellular traps collaborate to promote intravascular coagulation during sepsis in mice. Blood 129, 1357–1367 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. O’Reilly, D. et al. Platelets in pediatric and neonatal sepsis: Novel mediators of the inflammatory cascade. Pediatr. Res. 91, 359–367 (2021).

  18. Nyamundanda, G., Gormley, I. C., Fan, Y., Gallagher, W. M. & Brennan, L. Metsizer: Selecting the optimal sample size for metabolomic studies using an analysis based approach. BMC Bioinforma. 14, 338 (2013).

    Article  Google Scholar 

  19. Köstlin-Gille, N. et al. Epidemiology of early and late onset neonatal sepsis in very low birthweight infants: Data from the german neonatal network. Pediatr. Infect. Dis. J. 40, 255–259 (2021).

    Article  PubMed  Google Scholar 

  20. Cantey, J. B. & Prusakov, P. A proposed framework for the clinical management of neonatal "Culture-Negative" sepsis. J. Pediatr. 244, 203–211 (2022).

    Article  PubMed  Google Scholar 

  21. Murphy, C. A. et al. The effect of platelets on thrombin generation in cord blood and peripheral neonatal blood in the premature infant; the event study. Blood 138, 3188 (2021).

    Article  Google Scholar 

  22. Richardson, D. K., Corcoran, J. D., Escobar, G. J. & Lee, S. K. Snap-Ii and Snappe-Ii: Simplified newborn illness severity and mortality risk scores. J. Pediatr. 138, 92–100 (2001).

    Article  CAS  PubMed  Google Scholar 

  23. Parsons, M. E. M. et al. Platelet releasate proteome profiling reveals a core set of proteins with low variance between healthy adults. Proteomics 18, 1800219 (2018).

    Article  Google Scholar 

  24. Maguire, P. B. et al. Proteomic analysis reveals a strong association of Β-catenin with cadherin adherens junctions in resting human platelets. Proteomics 18, 1700419 (2018).

    Article  Google Scholar 

Download references

Acknowledgements

We would like to acknowledge the contribution of Ms.Mandy Daly (Irish Neonatal Health Alliance) for her assistance and input with regard to patient-public involvement.

Funding

DOR has been awarded the Irish Clinical Academic Training (ICAT) Programme, supported by the Wellcome Trust and the Health Research Board (grant number 203930/B/16/Z), the Health Service Executive, National Doctors Training and Planning, and the Health and Social Care, Research and Development Division, Northern Ireland.

Author information

Authors and Affiliations

  1. School of Biomolecular and Biomedical Science, University College Dublin, Dublin, 4, Ireland

    Daniel O’Reilly, Fionnuala Ní Áinle & Patricia Maguire

  2. Department of Neonatology, Rotunda Hospital, Dublin, 1, Ireland

    Daniel O’Reilly & Naomi Mc Callion

  3. Department of Neonatology, National Maternity Hospital, Dublin, 2, Ireland

    Daniel O’Reilly, Claire Anne Murphy, Carmel Maria Moore & Anna Curley

  4. School of Medicine, University College Dublin, Dublin, 4, Ireland

    Carmel Maria Moore

  5. Department of Haematology, Rotunda Hospital, Dublin, 1, Ireland

    Fionnuala Ní Áinle

  6. Department of Haematology, Mater Hospital, Dublin, 7, Ireland

    Fionnuala Ní Áinle

  7. School of Mathematics and Statistics, University College Dublin, Dublin, 4, Ireland

    Isobel Claire Gormley

  8. University of Rochester Medical Center, Rochester, NY, USA

    Craig N. Morrell

  9. Department of Paediatrics, Royal College of Surgeons in Ireland, Dublin, 2, Ireland

    Naomi Mc Callion

Authors
  1. Daniel O’Reilly
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Claire Anne Murphy
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Carmel Maria Moore
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fionnuala Ní Áinle
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Isobel Claire Gormley
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Craig N. Morrell
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Anna Curley
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Naomi Mc Callion
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Patricia Maguire
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Study designed by D.O.R., C.A.M., N.M.c.C., A.C. and P.M.. Statistical plan developed by I.C.G. and D.O.R.. Clinical protocol developed by D.O.R., C.A.M., C.M.M., F.N.A., N.M.c.C. and A.C.. Experimental design by D.O.R., C.N.M., P.M.. All authors reviewed this manuscript prior to submission.

Corresponding author

Correspondence to Daniel O’Reilly.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

O’Reilly, D., Murphy, C.A., Moore, C.M. et al. Markers of platelet activation foR identification of late onset sEpsis in infaNTs: PARENT study protocol. Pediatr Res 95, 852–856 (2024). https://doi.org/10.1038/s41390-023-02812-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41390-023-02812-x

Search

Advanced search

Quick links