Pediatric reference intervals: Gaps and recent advances

ABSTRACT

Clinical laboratory reference ranges serve as health-associated benchmarks that enable clinicians to interpret laboratory test results and facilitate clinical decision-making. Unfortunately, critical gaps currently exist in accurate and up-to-date pediatric reference ranges for accurate interpretation of laboratory tests performed in children and adolescents, which may contribute to erroneous diagnosis or misdiagnosis of many diseases. Several initiatives have been established internationally to address these gaps, including the KiGGS initiative in Germany, the Aussie Normals in Australia, the AACC-National Children Study in the USA, the NORICHILD Initiative in Scandinavia, and the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) program in Canada. Since 2009, CALIPER has recruited more than 12,000 healthy children and adolescents, thereby establishing a comprehensive database of pediatric reference ranges for over 185 biomarkers of health and disease (www.caliperdatabase.org). However, evidence gaps continue to exist for special markers and new laboratory instruments. To address these gaps, our team has recently completed or is currently undertaking studies to establish pediatric reference ranges for 1) chemistry and immunological markers on new analytical systems (Abbott Alinity, Siemens Attelica), 2) hematological markers on multiple platforms (Sysmex, Beckman, Mindray), 3) critical care markers on point of care testing platforms, 4) markers of inflammatory disease (cytokines, calprotectin, autoimmune), 5) markers of nutritional deficiency (essential trace elements), and 6) markers of environmental toxicity (heavy metals). CALIPER is also embarking on specific sub-studies regarding maternal, child, and adolescent health, such as the Mother & Child Health Initiative, COVID-19 Seroprevalence Study, and Lipid Metabolism in Adolescents with obesity. In this presentation, I will review the recent worldwide initiatives on pediatric reference ranges as well as discuss the concept and feasibility of common reference ranges. I will also discuss the progress made by the CALIPER program, the CALIPER database, and future research directions.