Biochemical Marker Reference Values across Pediatric, Adult, and Geriatric Ages: Establishment of Robust Pediatric and Adult Reference Intervals on the Basis of the Canadian Health Measures Survey

Abstract

BACKGROUND Biological covariates such as age and sex can markedly influence biochemical marker reference values, but no comprehensive study has examined such changes across pediatric, adult, and geriatric ages. The Canadian Health Measures Survey (CHMS) collected comprehensive nationwide health information and blood samples from children and adults in the household population and, in collaboration with the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER), examined biological changes in biochemical markers from pediatric to geriatric age, establishing a comprehensive reference interval database for routine disease biomarkers. METHODS The CHMS collected health information, physical measurements, and biosamples (blood and urine) from approximately 12 000 Canadians aged 3–79 years and measured 24 biochemical markers with the Ortho Vitros 5600 FS analyzer or a manual microplate. By use of CLSI C28-A3 guidelines, we determined age- and sex-specific reference intervals, including corresponding 90% CIs, on the basis of specific exclusion criteria. RESULTS Biochemical marker reference values exhibited dynamic changes from pediatric to geriatric age. Most biochemical markers required some combination of age and/or sex partitioning. Two or more age partitions were required for all analytes except bicarbonate, which remained constant throughout life. Additional sex partitioning was required for most biomarkers, except bicarbonate, total cholesterol, total protein, urine iodine, and potassium. CONCLUSIONS Understanding the fluctuations in biochemical markers over a wide age range provides important insight into biological processes and facilitates clinical application of biochemical markers to monitor manifestation of various disease states. The CHMS-CALIPER collaboration addresses this important evidence gap and allows the establishment of robust pediatric and adult reference intervals.

Complex Reference Values for Endocrine and Special Chemistry Biomarkers across Pediatric, Adult, and Geriatric Ages: Establishment of Robust Pediatric and Adult Reference Intervals on the Basis of the Canadian Health Measures Survey

“…Obesity is known to be a significant risk factor for diabetes, and the increased incidence of obesity with age observed here followed the same trend as the portion of participants excluded in the older age range. The same relationship is observed for glucose concentration, analyzed in Adeli et al (11 ), which further supports the presence of a greater number of older individuals in the Canadian population with diabetes and other components of the metabolic syndrome. Although Hb A 1c is not recommended for screening or diagnosis of diabetes in children or geriatric populations, these data are an important public health finding and are consistent with the rising rates of diabetes, obesity, metabolic syndrome, and cardiovascular disease in Canada and other Western countries (31,32 ).…”

“…Increased concentrations in older years likely reflect an age-associated increase in insulin resistance owing to higher incidence of overweight and obesity in older age, indicated in the online Supplemental Table 2 of Adeli et al (11 ).…”

“…Data are shown in online Supplemental Table 2 of Adeli et al (11 ). Exclusion criteria were applied to remove individuals who were pregnant, taking prescription medications, or diagnosed with a serious medical or chronic illness [refer to online Supplemental Table 3 of Adeli et al (11 )].…”

Transference and Validation of Reference Intervals

“…Adeli and colleagues present data from the CHMS-CALIPER formal reference interval study in 3 separate articles in this issue of Clinical Chemistry (2)(3)(4) It is the responsibility of individual laboratories or laboratory networks to use reference intervals that are appropriate for their methodologies and the population they serve, as specified by International Organization for Standardization (ISO) standard 15189 (5 ). Advice on how to do this is found in guidelines from the CLSI.…”

The Power of Asterisks

“…In this issue of Clinical Chemistry, Adeli and colleagues provide, in a series of 3 papers (2)(3)(4), an exceptional compilation of high-quality reference interval data. Following a protocol they developed for the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) 2 (5 ), which was undertaken to address the dearth of pediatric reference interval data, they arranged for roughly 12 000 reference individuals to provide blood and urine samples to be analyzed for a large number of common laboratory tests.…”