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. 2021 Apr;35(4):e23708.
doi: 10.1002/jcla.23708. Epub 2021 Jan 22.

Establishment of age- and sex-specific reference intervals for serum liver function tests in pediatric population aged 1-<18 years: A prospective study

Xuetong Zhu  1 , Kaijin Wang  1 , Qi Zhou  2 , Jiancheng Xu  1
Affiliations

Establishment of age- and sex-specific reference intervals for serum liver function tests in pediatric population aged 1-<18 years: A prospective study

Xuetong Zhu et al. J Clin Lab Anal. 2021 Apr.

Abstract

Background: The diagnosis, treatment, and prognosis of pediatric diseases rely on the accurate establishment of the reference interval (RI). This study aimed to establish pediatric RIs for liver function tests and evaluated the correlation of the analytes.

Methods: Pediatric population (aged 1-<18 years) was prospectively recruited in Jilin Province, China. Analytes detected by Ortho VITORS 5600 automatic biochemical analyzer. All strata were divided using the regression tree and Harris and Boyd's method. The dynamic changes of RI were evaluated by the lambda-mu-sigma method.

Results: Reference individuals were comprised of 6,322 children and adolescents. Age and sex differences were present in all analytes except serum total protein. The serum albumin, total protein, γ-glutamyl transferase, total bilirubin, and unconjugated bilirubin levels increased with age while serum aspartate aminotransferase was opposite. The serum alanine aminotransferase level reached a trough at the age of 5 and later steadily in males but slowly decreased in females. The serum alkaline phosphatase level dropped rapidly after reaching a peak at 9 years old in females and 12 years old in males. RIs were divided into 11 partitions at most and 5 partitions at least. The strongest correlation between analytes was total bilirubin and unconjugated bilirubin (r = 0.788), followed by total bilirubin and albumin (r = 0.511).

Conclusions: Analytes show unique dynamic changes in pediatric population. The correlations among liver function tests can inform future studies of particular variables. Age- and sex-special pediatric RIs should be established to help an accurate diagnosis of disease.

Keywords: adolescent; alkaline phosphatase; children; liver function; reference interval.

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Conflict of interest statement

The authors stated that there are no conflicts of interest regarding the publication of this article.

Figures

FIGURE 1
FIGURE 1
Protocol for establishment of pediatric reference intervals
FIGURE 2
FIGURE 2
Age‐ and sex‐specific reference interval of liver function tests in the healthy pediatric population
FIGURE 3
FIGURE 3
Age‐ and sex‐specific continuous percentile curve of A, ALB; B, TP; C, ALT; D, AST; E, GGT; F, ALP; G, TBIL; H, Bu
FIGURE 4
FIGURE 4
Spearman correlation heat map among 11 variables in the healthy pediatric population aged 1–<18 years. The strength of the correlation between two variables is represented by the color of the square at the intersection of those variables
See this image and copyright information in PMC

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