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Current Gaps and Initiatives in Paediatric Reference Intervals


Laboratories and clinicians have depended on scattered and incomplete data as a source of paediatric reference intervals. Comprehensive and adequately partitioned paediatric reference intervals have only been available for a limited number of disease biomarkers, while most of the available reference intervals are incomplete, cover a limited age interval and do not always cover both genders. Paediatric reference intervals have not been determined for new and emerging biomarkers. In addition, almost all available reference intervals were determined only on Caucasian populations; application to other ethnic groups may not be appropriate for some biomarkers. Many of the available reference intervals were determined decades ago on older and less accurate laboratory instruments and methodologies. Finally, reference intervals have typically been derived from samples collected from hospitalized patients and may not reflect values in healthy populations.

Accrediting and licensing organizations/regulatory bodies governing medical laboratory best practices require that individual laboratories establish or verify reference intervals for all quantitative test methods; the exception being for tests that employ decision cut-off limits (e.g. cholesterol, hemoglobin A1C). The undertaking in terms of time, resources, and costs to each laboratory is significant. This is especially difficult with paediatric populations that require age partitioning based on child development.


Several large national studies have recently been initiated in a number of different countries. They aim to provide a comprehensive description of children’s health and to understand the role of various determinants of health in children.
In Canada, Statistics Canada is conducting the Canada Health Measures Survey (http://www.statcan.gc.ca), launched in 2007 and targeted to the entire population. The study collects health information by physical examination and interview, and collects blood and urine samples. The emphasis is on analysis of different nutritional, metabolic, cardiovascular, kidney disease, environmental toxic exposure, and infectious disease biomarkers. The data obtained from children may be used to establish paediatric reference intervals. CALIPER has collaborated with Statistics Canada to develop reference intervals based on data collected from Cycles 1 and 2 of the Canadian Health Measures Survey. The results of this collaboration have been published in Clinical Chemistry.

National Children’s Study in the United States (http://www.nationalchildrensstudy.gov) is following a large number of children across the United States from birth to 21 years of age to examine children’s health and the effect of various environmental, genetic and social factors on children’s growth and development. This study also aims to establish new paediatric reference intervals.

In Germany, a nationwide health survey targeting children, the German Health Interview and Examination Survey for Children and Adolescents (KiGGS; http://www.kiggs.de) was initiated in 2003. It is a long-term comprehensive study that aims to examine different aspects of children’s physical and mental health. The study includes measurements of laboratory parameters and the establishment of reference intervals and cutoff values for analytes of interest for children aged 0 –17 years.

Children’s Health Improvement through Laboratory Diagnostics (CHILDx; http://www.childx.org) developed by ARUP and the University of Utah Department of Pathology, is conducting a paediatric reference interval project for children aged 6 months – 17 years in Salt Lake City, Utah.