Objective and rationale: Reference intervals provided on laboratory reports are essential for appropriate interpretation of test results, and can significantly impact clinical decision-making and the quality of patient care. Careful determination and/or validation of reference intervals by the laboratory for use in the patient population it serves are therefore important to ensure their proper utility. Unfortunately, critical gaps currently exist in accurate and up-to-date pediatric reference intervals for accurate interpretation of laboratory tests performed in children and adolescents. These critical gaps in the available pediatric laboratory reference intervals have the clear potential of contributing to erroneous diagnosis or misdiagnosis of many diseases of childhood and adolescence. Most of the available "normal" ranges for laboratory tests were determined over 2 decades ago on older instruments and technologies, and are no longer relevant considering the current testing technology used by clinical laboratories. It is thus critical and of utmost urgency that a more acceptable and comprehensive database be established.
Discussion and conclusion: In the present review, we discuss the considerations and challenges faced when generating and validating reference intervals in accordance to the current guidelines published by the Clinical Laboratory Standards Institute (CLSI). We raise particular attention to the present-day deficiencies in available pediatric reference intervals, and highlight the special issues and unique difficulties that are additionally faced when establishing reference intervals in children. Finally, we highlight a recent Canadian initiative, the CALIPER project, whose mandate is to establish and maintain a database of comprehensive and up-to-date pediatric reference intervals to be eventually made available to all clinical laboratories worldwide.