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  • Clinical Research Article
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Inflammation, sepsis severity and neurodevelopmental outcomes of late-onset sepsis in preterm neonates

Pediatric Research volume 94, pages 2026–2032 (2023)Cite this article

Abstract

Background

The aim of this study was to investigate the association between inflammatory biomarkers (C-reactive protein (CRP), procalcitonin (PCT) and interleukin-6 (IL-6)) and sepsis severity (neonatal-Sequential-Organ-Failure-Assessment (nSOFA)) and neurodevelopmental outcomes at 2 years, among very preterm neonates.

Methods

Data on preterm neonates (gestational age <30 weeks) from 2016 until 2020 were reviewed. Outcomes of interest were NDI (no, mild, severe) and the motor and cognitive score on the Dutch-Bayley-Scales-of-Infant-and-Toddler-Development (Bayley-III-NL) assessed at the corrected age of 2 years. Logistic and linear regression analysis were used for categorical and continuous outcomes, respectively. All analyses were adjusted for gestational age, sex and birthweight-for-gestational-age SD-score.

Results

In total 410 patients were eligible for analysis. Maximum CRP concentrations were associated with lower motor and cognitive scores (effect estimate −0.03 points,(95% CI −0.07; −0.00) and −0.03 points,(95% CI −0.06; −0.004), respectively) and increased risk of severe NDI (odds ratio (OR) 1.01, (95% CI 1.00; 1.01)). High nSOFA scores (≥4) during sepsis episodes were associated with an increased risk of mild NDI (OR 2.01, (95% CI 1.34; 3.03)). There were no consistent associations between IL-6, PCT and the outcomes of interest.

Conclusion

High CRP concentrations and sepsis severity in preterm neonates seem to be associated with neurodevelopmental outcomes in survivors at the age of 2 years.

Impact statement

  • The level of inflammation and sepsis severity are associated with neurodevelopmental outcome in preterm neonates at 2 years of corrected age.

  • Sepsis is a major health issue in preterm neonates and can lead to brain damage and impaired neurodevelopment. Biomarkers can be determined to assess the level of inflammation. However, the relation of inflammatory biomarkers with neurodevelopmental outcome is not known.

  • The level of inflammation and sepsis severity are related to neurodevelopmental outcome in preterm neonates. Maximum CRP concentration and high nSOFA scores are associated with an increased risk of neurodevelopmental impairment in survivors at the corrected age of 2 years.

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Fig. 1: Flow chart of the study population.

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Data availability

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

Code availability

The code that support the findings of this study are available on request from the corresponding author (SPSS (IBM SPSS Statistics for Windows, Version 25.0) and R (R Core Team (2017), Vienna, Austria)).

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Funding

H.R.T. received an unrestricted research grant from Roche Diagnostics (F. Hoffmann-La Roche Ltd.) to support the conduct of this study.

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Author notes

  1. These authors contributed equally: Şerife Kurul, Famke L. M. Beckers.

Authors and Affiliations

  1. Department of Neonatal and Pediatric Intensive Care, Division of Neonatology, Erasmus Medical Center-Sophia Children’s Hospital, Rotterdam, the Netherlands

    Şerife Kurul, Famke L. M. Beckers, Marijn J. Vermeulen, Jasmin E. Hasbek, Sinno H. P. Simons, Irwin K. M. Reiss & H. Rob Taal

  2. Department of Child and Adolescent Psychiatry/Psychology, Erasmus Medical Center, Rotterdam, the Netherlands

    Jill Suurland

  3. Department of Clinical Chemistry, Erasmus Medical Center, Rotterdam, the Netherlands

    Christian R. B. Ramakers

Authors
  1. Şerife Kurul
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Contributions

H.R.T. conceptualized and designed the study, supervised data collection and reviewed and revised the manuscript. S.K. and F.L.M.B. collected data, carried out the initial analyses, and drafted, reviewed and revised the manuscript. C.R.B.R. and J.E.H. collected data and reviewed and revised the manuscript. M.J.V., J.S., S.H.P.S. and I.K.M.R. critically reviewed the manuscript for important intellectual content and reviewed and revised the manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Corresponding author

Correspondence to H. Rob Taal.

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Competing interests

The authors declare no competing interests.

Ethics approval

The study was approved by the local ethical board of the Erasmus Medical Center (MEC-2022-0062).

Consent to participate

Written informed parental consent was obtained, as standard of care, during admittance to the NICU, or at first visit to the outpatient clinic and at the follow up visit at corrected age of 2 years.

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Kurul, Ş., Beckers, F.L.M., Vermeulen, M.J. et al. Inflammation, sepsis severity and neurodevelopmental outcomes of late-onset sepsis in preterm neonates. Pediatr Res 94, 2026–2032 (2023). https://doi.org/10.1038/s41390-023-02742-8

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