Studies conducted by Canadian researchers shed new light on pediatric, adult, and geriatric reference intervals for 53 hematology, chemistry, and immunoassay-based biomarkers. The analysis paves the way to harmonize reference intervals across Canada and elsewhere.

The Canadian Health Measures Survey (CHMS) and Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) collaborated on three studies that appeared in the August issue of Clinical Chemistry. Collectively, this work describes reference intervals for 16 hematology measures, 13 immunoassay-based special chemistry and endocrinology markers, and 24 biochemistry analytes.

To develop these partitioned sets of intervals, the CHMS collected nearly 12,000 data and blood samples from community participants whose ages spanned several generations, from 3 to 79 years. The biospecimens represented approximately 96% of Canada’s household population.

Reference intervals serve as an important tool in a laboratory’s arsenal to help interpret test results. “Although laboratories are well versed in method verification and validation to assess if methods are fit-for-purpose, less importance is commonly put on selecting the most appropriate reference interval to determine whether an individual is healthy,” a related editorial in Clinical Chemistry noted.

In one of the studies, CHMS used this large dataset to assess hematologic changes throughout various life stages.

Establishing reference intervals for hematology has been particularly difficult. “Appropriate age- and sex-specific reference intervals for hematology are often lacking or incomplete across a broad range of ages, as studies tend to establish their intervals on select subsets of the population, focusing on either children or adults as distinct entities,” the article on the findings stated. In addition, small children and the geriatric population come with their own set of challenges in providing researchers with a robust dataset of healthy individuals.

The advantage of the study’s expansive dataset is it “allowed observation of dynamic biological profiles of several hematology markers and the establishment of comprehensive age- and sex-specific reference intervals that may contribute to accurate monitoring of pediatric, adult, and geriatric patients,” the authors noted.

Researchers found that “hemoglobin concentration, hematocrit, and the other RBC indices reflect the same biological parameters and show similar variability throughout life. Male and female levels are similar in early childhood and rise slowly until 10 years of age before sex differences are observed,” the article stated.

For the study that measured the 13 immunoassay-based special chemistry and endocrine markers, researchers “observed fluctuations in biomarker reference values across the pediatric, adult, and geriatric age range, with stratification required on the basis of age for all analytes.”

Similarly, the study on the 24 biochemical markers found that these reference values demonstrated significant changes across the human lifespan. “Most biochemical markers required some combination of age and/or sex partitioning,” authors of this study observed. “Two or more age partitions were required of all analytes except bicarbonate, which remained constant throughout life.”

Collectively, the reference intervals that came out of the CHMS-CALIPER studies provide “statistically the most robust data to date for a total of 53 different chemistry, immunoassay-based, and hematology analytes and parameters in a Canadian population…The comprehensiveness of the population analyzed (ages 3–79 years) means the authors provide a considerably more meaningful account of biological changes to every analyte by age and sex, a feat rarely achieved in reference interval examination,” according to the editorial.