The Pediatric Reference Intervals in China (PRINCE) was initiated to establish the reference intervals (RIs) of Chinese children, as well as to make it possible to compare the variability of biochemical markers among countries internationally.
Healthy participants, aged up to 20 years, from 11 provinces across China, were enrolled in PRINCE and according to a standard screening procedure, that included a questionnaire survey, physical examinations and laboratory tests. Fasting venous blood specimens were collected. All serum specimens were analyzed with Cobas C702 in the center laboratory, i.e. clinical laboratory of Beijing Children’s Hospital, with certified qualification (ISO15189). The nonparametric method recommended by Clinical Laboratory Standards Institute guidelines, was used to calculate the age- and sex-specified RIs.
Among the 15,150 participants enrolled, 12,352 children (6,093 males and 6,259 females) were included to calculate RIs. The RIs for total protein, albumin, globulin, calcium, phosphate, potassium, sodium, chlorine, alkaline phosphatase, γ-glutamyl transpeptadase, alanine aminotransferase, aspartate aminotransferase, creatinine and urea were established by age- or sex-partitions. Most biochemical markers displayed larger variability and higher dispersion during the periods between 28 days and 1 year old, and included 4–6 age partitions commonly during 1 to <20 years old. In addition, differences of RIs between sexes usually occurs around the initiation of puberty at 12–13 years old.
The age- and sex-specified RIs of 14 biochemical markers in PRINCE study can provide a solid reference, which will be transferred into relevant RIs for other clinical laboratory’s platforms according to the CLSI guidelines.
Funding source: National Health Commission of the People’s Republic of China
Award Identifier / Grant number: 2017374
We thank the staff members of the PRINCE study team. Special thanks is also due to all participants for their involvement, as well as their parents for their supports during the study. We would also like to that Dr. Ali Abbas for editing the manuscripts’ language.
Research funding: The grand from Medical hospital authority, National Health Commission of the People’s Republic of China (No. 2017374).
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission. PX, PY, ZC, ZM, YH, CS, LG, JY, GZ, CD, XJ, CH, and XY were contributed equally for writing the manuscript, as well as the organization and implementation of the study in each center, including epidemiological investigation, physical examination, specimen collection and transfer. MR, ZJ, SY, WY, LQ, HL, RN, CY, ZW, MJ were contributed the specimen management, laboratory test and quality control. YR, PX, and PY were in charge of the epidemiological methodology design, data management and data analysis. CW, SW, and NX were contributed equally for conceive the study.
Competing interests: Authors state no conflict of interest.
Informed consent: Informed consent was obtained from each participant’s legally authorized representative (parent or guardian) in the case of children aged less than 8 years. Otherwise, the informed consent was obtained from both the child and their legally authorized representative.
Ethical approval: The PRINCE study was approved by The Institutional Review Board of Beijing Children’s Hospital (IEC-C-028-A10-V.05).
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