Abstract:
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: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: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: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.
journal_name
Clin Biochemjournal_title
Clinical biochemistryauthors
Asgari S,Higgins V,McCudden C,Adeli Kdoi
10.1016/j.clinbiochem.2019.08.010subject
Has Abstractpub_date
2019-11-01 00:00:00pages
82-89eissn
0009-9120issn
1873-2933pii
S0009-9120(19)30785-4journal_volume
73pub_type
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