Serum neuron-specific enolase – reference interval in Danish children and the impact of preanalytical factors
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Jacob Rudjord Therkildsen
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Cindy Søndersø Knudsen
Abstract
Objectives
Neuron-specific enolase (NSE) is a clinically relevant biomarker used in the assessment of neuronal damage and in the diagnosis and monitoring of certain cancers. Despite its diagnostic importance, paediatric-specific reference intervals (RIs) for NSE are currently lacking. This study aimed to establish paediatric RIs for NSE in serum and to evaluate the influence of preanalytical factors on NSE measurements.
Methods
Residual serum samples from routine allergy testing in 242 Danish children (aged 0.1–17.9 years) were analysed using the Roche Elecsys® NSE assay on a Cobas platform. Both traditional non-parametric, age-partitioned RIs and continuous RIs derived via quantile regression were established. In addition, we assessed the impact of preanalytical variables, including haemolysis, and evaluated a previously proposed correction method for haemolysed samples within this cohort.
Results
Both the non-parametric and continuous approaches yielded consistent RIs, showing an age-dependent decline in serum NSE concentrations irrespective of sex. The traditional age-partitioned RI (95th percentile, one-sided) indicated upper limits of 36.9 μg/L and 32.0 μg/L for the age groups 0–5 and 6–17 years of age, based on samples with haemolysis <10 mg/dL haemoglobin.
Conclusions
This study defines age-specific paediatric RIs for serum NSE, demonstrating a physiological decline with age and highlighting higher NSE levels in healthy children compared to adults. Furthermore, within a limited range, a previously proposed simple linear correction method was validated for adjusting NSE values in mildly haemolysed samples using the newly established RIs.
Acknowledgments
The authors would like to sincerely thank laboratory technician Katrine Bremer for organising the analysis of blood samples and conducting preanalytical experiments.
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Research ethics: Not applicable. According to Danish legislation, no approval from an Ethical Committee was required for the present study using anonymized biological material only.
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Informed consent: Not applicable.
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Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
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Use of Large Language Models, AI and Machine Learning Tools: None declared.
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Conflict of interest: The authors state no conflict of interest.
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Research funding: This study was funded by the Department of Clinical Biochemistry, Aarhus University Hospital.
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Data availability: The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.
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Supplementary Material
This article contains supplementary material (https://doi.org/10.1515/cclm-2025-0582).
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