Continuous reference intervals for 21 biochemical and hematological analytes in healthy Chinese children and adolescents: The PRINCE study

Critical gaps have existed in pediatric reference intervals in China. In this study, we presented the sex and age distributions of 21 laboratory analytes from childhood to adolescence, and established the corresponding continuous reference intervals based on direct samples.We used the data from the Pediatric Reference Intervals in China (PRINCE), which is a nation-wide cross-sectional study enrolling 15,150 healthy children and adolescents aged 0 - <20 years from 11 centers across China. Blood samples were collected and analyzed by trained staff following standard operating procedures. Biochemical tests were performed with Cobas C702 at the central laboratory, and hematological tests were performed with Sysmex XE, XN, or XS that satisfy the national standards at each participating center. Children younger than 3 months were excluded due to high neonatal variability and insufficient samples. Continuous reference intervals were calculated using the generalized additive models for location, shape, and scale, and were validated among another 387 healthy volunteers.We provided pediatric continuous reference intervals for 21 commonly used biochemical and hematological analytes in China, and depicted the changes in analyte concentrations from 3 months to 20 years. The out-of-range values for all analytes were less than 10%, indicating a well applicability of the continuous reference intervals to the general pediatric population.This is the first comprehensive report of continuous reference intervals based on healthy Chinese children, reflecting the complex dynamic trends of analytes from infancy to adulthood. Applying continuous reference intervals to clinical practice would not only improve the laboratory test result interpretation, but also help better clinical decision making.