Pediatric reference intervals: critical gap analysis and establishment of a national initiative.

The practice of pediatric laboratory medicine involves unique challenges related to development, nutrition, growth and diseases during different periods of infancy, childhood and adolescence. Pediatric patients require a unique medical approach, as significant differences exist in disease frequencies, specimen collection, test performance and test interpretation. In the last two decades, clinical diagnostic laboratories have witnessed a tremendous increase in the variety of biomarkers and major technology changes. Screening, diagnosis and monitoring of almost all pediatric diseases requires the measurement of a wide range of disease biomarkers with varying degree of clinical specificity and sensitivity. These biomarkers are commonly measured in clinical laboratories and guide important clinical decisions. Physicians rely on the availability of appropriate and reliable reference (or normal) intervals to accurately interpret laboratory test results with data collected during medical interview and clinical examination. According to the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) guidelines, reference intervals are defined as the central 95% of values from a reference population bound by lower and upper reference limits (2.5% above and below the interval) at designated percentiles. In order to validate a marker for use in the diagnosis of clinical disorders, the hormones or chemical substances must be measured in large healthy populations of various ages, ethnicities and both genders to establish appropriate reference intervals. Although health professionals understand the importance of reference intervals, many laboratories still do not have comprehensive reference interval data, especially for the pediatric population. Pediatric specimen collection provides challenges and is a major concern for health care providers. It is frequently difficult to obtain sufficient volumes of blood or urine from pediatric patients. Common reference intervals have not been implemented in Canada due to lack of harmonization of methods and differences in patient populations. Consequently, clinical laboratory accreditation organizations and licensing agencies require that each laboratory verify or establish reference intervals for each method. To provide such reference intervals requires selection criteria for suitable reference individuals, defined conditions for specimen collection and analysis, method selection to determine reference limits and validation of the reference interval.