Abstract
Objectives
Marked physiological changes in growth and development present challenges in defining pediatric reference intervals for biomarkers of health and disease. Lambda, Mu, and Sigma (LMS)-based statistical modeling provides a continuous normal distribution by negating skewness and variation, and is commonly used to establish growth charts. Such LMS reference curves are suggested to enhance laboratory test result interpretation. The current study establishes LMS-based continuous reference percentiles for 14 biomarkers in the CALIPER cohort of healthy children and adolescents.
Methods
Data from healthy children and adolescents aged 1–<19 years were used to establish continuous reference percentiles using a novel LMS-based statistical method, including 2.5th, 25th, 50th, 75th, and 97.5th percentiles. The LMS approach applies a Box-Cox data transformation and summarizes continuous distributions by age via three curves: skewness (Lambda), median (Mu), and coefficient of variation (Sigma).
Results
LMS-based percentiles and z-scores were generated for 14 common pediatric biomarkers that demonstrate dynamic concentration patterns with age (e.g., alkaline phosphatase) and/or wherein the magnitude of difference from the population mean may be clinically relevant (e.g., triglycerides). The LMS model captured age- and sex-specific distributions accurately and was not substantially influenced by outlying points.
Conclusions
This is the first study to establish LMS-based continuous reference percentiles for biochemical markers in a healthy Canadian pediatric population. The current LMS-based approach builds upon previous continuous reference interval models by providing graded percentiles to improve test result interpretation, particularly with repeated measures over time. This method may assist in facilitating a patient-centered approach to laboratory medicine.
Funding source: Canadian Institute for Health Research
Award Identifier / Grant number: 353989
Acknowledgments
We would like to thank the CALIPER participants, families, and volunteers who have made this research possible.
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Research funding: This work is supported by a Canadian Institute for Health Research (CIHR) Foundation Grant to K.A. [grant number: 353989], a CIHR Doctoral Award to M.K.B, and a CIHR Master’s Award and Banting and Best Diabetes Centre Graduate Studentship to S.W.
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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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Competing interests: Authors state no conflict of interest.
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Informed consent: Informed consent was obtained from all individuals included in this study.
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Ethical approval: Research involving human subjects complied with all relevant national regulations, institutional policies and is in accordance with the tenets of the Helsinki Declaration (as revised in 2013) and has been approved by the authors’ Institutional Review Board at the Hospital for Sick Children.
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Supplementary Material
This article contains supplementary material (https://doi.org/10.1515/cclm-2022-1077).
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