Continuous reference intervals for 38 biochemical markers in healthy children and adolescents: Comparisons to traditionally partitioned reference intervals.
Biochemical markers
Continuous reference intervals
Pediatric
Journal
Clinical biochemistry
ISSN: 1873-2933
Titre abrégé: Clin Biochem
Pays: United States
ID NLM: 0133660
Informations de publication
Date de publication:
Nov 2019
Nov 2019
Historique:
received:
16
07
2019
revised:
11
08
2019
accepted:
21
08
2019
pubmed:
26
8
2019
medline:
22
11
2019
entrez:
26
8
2019
Statut:
ppublish
Résumé
Reference intervals have traditionally been partitioned by age based on statistical significance and physiological relevance. However, analyte concentration does not change abruptly with age, but rather dynamically. In this study, we establish biochemical marker continuous reference intervals for a Canadian population using healthy pediatric reference individuals and compare these to partitioned reference intervals. Continuous reference intervals spanning 1-18.5 years of age were established using data from healthy CALIPER children and adolescents aged 6 months- < 19 years. Continuous reference intervals (i.e. 2.5th and 97.5th quantiles) were generated by nonparametric quantile regression via penalized splines with non-crossing constraints. Abnormal flagging rates of established continuous reference intervals were compared to previously established age-partitioned CALIPER reference intervals for five biochemical markers using internal (CALIPER) and external (i.e. Canadian Health Measures Survey (CHMS)) datasets. Continuous reference intervals were determined for 38 biochemical markers, with 21 markers requiring sex-specific reference intervals. Despite similar total flagging rates to partitioned reference intervals, continuous reference intervals appeared to provide a more consistent and accurate estimation of reference limits for biomarkers with more complex age-related changes, including alkaline phosphatase and phosphate. This is the first report of continuous biochemical marker reference intervals based on a healthy Canadian pediatric population. Reference limit point estimates based on continuous reference intervals are provided to aid clinical implementation. Continuous reference intervals offer a better estimation of dynamic changes in biochemical marker reference values with age, resulting in improved laboratory test result interpretation and clinical decision making in pediatrics.
Sections du résumé
BACKGROUND
BACKGROUND
Reference intervals have traditionally been partitioned by age based on statistical significance and physiological relevance. However, analyte concentration does not change abruptly with age, but rather dynamically. In this study, we establish biochemical marker continuous reference intervals for a Canadian population using healthy pediatric reference individuals and compare these to partitioned reference intervals.
METHODS
METHODS
Continuous reference intervals spanning 1-18.5 years of age were established using data from healthy CALIPER children and adolescents aged 6 months- < 19 years. Continuous reference intervals (i.e. 2.5th and 97.5th quantiles) were generated by nonparametric quantile regression via penalized splines with non-crossing constraints. Abnormal flagging rates of established continuous reference intervals were compared to previously established age-partitioned CALIPER reference intervals for five biochemical markers using internal (CALIPER) and external (i.e. Canadian Health Measures Survey (CHMS)) datasets.
RESULTS
RESULTS
Continuous reference intervals were determined for 38 biochemical markers, with 21 markers requiring sex-specific reference intervals. Despite similar total flagging rates to partitioned reference intervals, continuous reference intervals appeared to provide a more consistent and accurate estimation of reference limits for biomarkers with more complex age-related changes, including alkaline phosphatase and phosphate.
CONCLUSIONS
CONCLUSIONS
This is the first report of continuous biochemical marker reference intervals based on a healthy Canadian pediatric population. Reference limit point estimates based on continuous reference intervals are provided to aid clinical implementation. Continuous reference intervals offer a better estimation of dynamic changes in biochemical marker reference values with age, resulting in improved laboratory test result interpretation and clinical decision making in pediatrics.
Identifiants
pubmed: 31445880
pii: S0009-9120(19)30785-4
doi: 10.1016/j.clinbiochem.2019.08.010
pii:
doi:
Substances chimiques
Biomarkers
0
Types de publication
Clinical Trial
Comparative Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
82-89Informations de copyright
Copyright © 2019 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.