Neurofilament light chain: serum reference intervals in Danish children aged 0-17 years

Abstract

Elevated levels of neurofilament light chain (NfL) in the blood is an unspecific biomarker for damage to neuronal axons. The measurement of NfL levels in the blood can provide useful information for monitoring and prognostication of various neurological disorders in children, but a reference interval (RI) is needed before the clinical implementation of the biomarker. We aimed to establish a RI for children aged 0–17 years. Serum samples from 292 healthy reference subjects aged 0.4–17.9 years were analysed by a single-molecule array (Simoa®) established for routine clinical use. Non-parametric quantile regression was used to model a continuous RI, and a traditional age-partitioned non-parametric RI was established according to Clinical and Laboratory Standard Institute (CLSI) guideline C28-A3. Furthermore, we investigated the effect of hemolysis on assay performance. The traditional age-partitioned non-parametric RI for the age group <3 years was 3.5–16.6 ng/L and 2.1–13.9 ng/L in the age group ≥3 years, respectively. The continuous RI showed an age-dependent decrease in median NfL levels in the first three years of life which was also evident in the age-partitioning of the traditional RI. We found no difference between sexes and no impact of hemolysis on the NfL test results. This study establishes a pediatric RI for serum NfL and lays the groundwork for its future use in clinical practice.

Keywords:

• Neurofilament protein L
• children
• reference interval
• serum
• biomarker
• hemolysis

Acknowledgements

The authors wish to thank Charlotte Noerby Pedersen and biomedical laboratory technicians Katrine Bremer and Arnaq Hammeken for organizing the analysis of the blood samples. We also wish to thank Christian Gundesen for developing the computer-algorithm used to identify the study population.

Informed consent/ethical approval

According to Danish law this study is categorized as a quality assurance project and exempted from informed consent and ethical approval.

Authors’ contributions

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

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The study was funded by the Department of Clinical Biochemistry, Aarhus University Hospital.