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Pediatric reference intervals for serum neurofilament light and glial fibrillary acidic protein using the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) cohort

  • Sophie Stukas ORCID logo , Jennifer Cooper ORCID logo , Victoria Higgins , Daniel Holmes , Khosrow Adeli and Cheryl L. Wellington EMAIL logo
Published/Copyright: October 27, 2023
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 62 Issue 4

Abstract

Objectives

Blood biomarkers have the potential to transform diagnosis and prognosis for multiple neurological indications. Establishing normative data is a critical benchmark in the analytical validation process. Normative data are important in children as little is known about how brain development may impact potential biomarkers. The objective of this study is to generate pediatric reference intervals (RIs) for serum neurofilament light (NfL), an axonal marker, and glial fibrillary acidic protein (GFAP), an astrocytic marker.

Methods

Serum from healthy children and adolescents aged 1 to <19 years were obtained from the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) cohort. Serum NfL (n=300) and GFAP (n=316) were quantified using Simoa technology, and discrete RI (2.5th and 97.5th percentiles) and continuous RI (5th and 95th percentiles) were generated.

Results

While there was no association with sex, there was a statistically significant (p<0.0001) negative association between age and serum NfL (Rho −0.400) and GFAP (Rho −0.749). Two statistically significant age partitions were generated for NfL: age 1 to <10 years (lower, upper limit; 3.13, 20.6 pg/mL) and 10 to <19 years (1.82, 7.44 pg/mL). For GFAP, three statistically significant age partitions were generated: age 1 to <3.5 years (80.4, 601 pg/mL); 3.5 to <11 years (50.7, 224 pg/mL); and 11 to <19 years (26.2, 119 pg/mL).

Conclusions

Taken together with the literature on adults, NfL and GFAP display U-shaped curves with high levels in infants, decreasing levels during childhood, a plateau during adolescence and early adulthood and increasing levels in seniors. These normative data are expected to inform future pediatric studies on the importance of age on neurological blood biomarkers.

Keywords: neurofilament light (NfL); glial fibrillary acidic protein (GFAP); blood biomarker; pediatric; reference intervals; neurology
Corresponding author: Cheryl L. Wellington, PhD, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, 2215 Westbrook Mall, Room 5650-33, V6T 1Z3, Vancouver, BC, Canada; and Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada; and International Collaboration on Repair Discoveries (ICORD), Blusson Spinal Cord Center, University of British Columbia, Vancouver, BC, Canada; and School of Biomedical Engineering (SBME), University of British Columbia, Vancouver, BC, Canada, Phone: 604-827-3769, E-mail:

Funding source: Canadian Institutes of Health Research

Funding source: Canadian Traumatic Brain Injury Research Consortium

Acknowledgments

We are grateful to all of the CALPER participants and their families and the research and clinical staff that assisted with the study.

  1. Research ethics: The research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance the tenets of the Helsinki Declaration and has been approved by the Institutional Review Boards of The Hospital for Sick Children (#1000010867) and Mount Sinai Hospital, Toronto, Canada and The University of British Columbia, Vancouver, Canada (H16-02548).

  2. Informed consent: Informed consent was obtained from all individuals included in this study, or their legal guardians or wards.

  3. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  4. Competing interests: The authors report no competing interests.

  5. Research funding: This study was funded by Canadian Traumatic Brain Injury Research Consortium (CTRC), funded by Brain Canada and the Canadian Institutes of Health Research (to CLW and KA).

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Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/cclm-2023-0660).

Received: 2023-06-27
Accepted: 2023-10-13
Published Online: 2023-10-27
Published in Print: 2024-03-25

© 2023 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/cclm-2023-0660
Keywords for this article
neurofilament light (NfL); glial fibrillary acidic protein (GFAP); blood biomarker; pediatric; reference intervals; neurology

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Value-based laboratory medicine: the time is now
  4. Review
  5. Cardiovascular risk evaluation in pregnancy: focus on cardiac specific biomarkers
  6. Opinion Papers
  7. From volume to value: a watershed moment for the clinical laboratory
  8. APS calculator: a data-driven tool for setting outcome-based analytical performance specifications for measurement uncertainty using specific clinical requirements and population data
  9. Guidelines and Recommendations
  10. Analytical interference of intravascular contrast agents with clinical laboratory tests: a joint guideline by the ESUR Contrast Media Safety Committee and the Preanalytical Phase Working Group of the EFLM Science Committee
  11. Genetics and Molecular Diagnostics
  12. Specifications of qPCR based epigenetic immune cell quantification
  13. General Clinical Chemistry and Laboratory Medicine
  14. An appraisal of the practice of duplicate testing for the detection of irregular analytical errors
  15. Machine learning-based nonlinear regression-adjusted real-time quality control modeling: a multi-center study
  16. The effect of ratios upon improving patient-based real-time quality control (PBRTQC) performance
  17. Diagnostic sample transport via pneumatic tube systems: data logger and their algorithms are sensitive to transport effects
  18. Ambulatory human chorionic gonadotrophin (hCG) testing: a verification of two hCG point of care devices
  19. Monitoring patients with celiac disease on gluten free diet: different outcomes comparing three tissue transglutaminase IgA assays
  20. Verification, implementation and harmonization of automated chemiluminescent immunoassays for MPO- and PR3-ANCA detection
  21. Performance evaluation of a novel platelet count parameter, hybrid platelet count, on the BC-780 automated hematology analyzer
  22. Reference Values and Biological Variations
  23. Pediatric reference intervals for serum neurofilament light and glial fibrillary acidic protein using the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) cohort
  24. Biological variation of serum neopterin concentrations in apparently healthy individuals
  25. Short-term biological variation of serum tryptase
  26. Cancer Diagnostics
  27. Quantification of the lung cancer tumor marker CYFRA 21-1 using protein precipitation, immunoaffinity bottom-up LC-MS/MS
  28. Cardiovascular Diseases
  29. Prognostic significance of chronic myocardial injury diagnosed by three different cardiac troponin assays in patients admitted with suspected acute coronary syndrome
  30. Deep learning-based NT-proBNP prediction from the ECG for risk assessment in the community
  31. Diabetes
  32. Innovations in HbA1c analysis: finding the balance between speed and accuracy. An investigation of a potential new Secondary Reference Measurement Procedure for the IFCC
  33. Precise glucose measurement in sodium fluoride-citrate plasma affects estimates of prevalence in diabetes and prediabetes
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  35. Urinary phenotyping of SARS-CoV-2 infection connects clinical diagnostics with metabolomics and uncovers impaired NAD+ pathway and SIRT1 activation
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