Establishment of reference interval of vitamin A for Chinese children and adolescents based on expectation-maximization algorithm

Abstract

Objective: To establish the reference interval of vitamin A for Chinese children and adolescents by indirect approach. Method: The serum retinol samples from 28 provinces, autonomous regions and municipalities in China between January 2016 and June 2019 were examined by high performance liquid chromatography in third-party clinical laboratory institutions. Using a cross-sectional study, descriptive statistics of serum vitamin A levels in children and adolescents aged 0-18 years were carried out in population, region and season. The distribution parameters of vitamin A levels were calculated iteratively by the expectation-maximization (EM) algorithm, and the reference interval was established. Results: A total of 1 096 597 cases were included in the analysis, including 631 017 males and 465 580 females, with a median age of 3(1, 6) years. Before the age of 4 years, the median serum vitamin A level increased with age [median level and its quartiles was 0.15 (0.11, 0.18) mg/L for neonates, 0.23 (0.18, 0.29) mg/L for infants aged below 1 year, and 0.27 (0.20, 0.34) mg/L for kids aged 1-<4 years]. The median serum vitamin A level was stable at the age of 4-8 years (median level ranged from 0.27 to 0.29 mg/L). Afterwards, the median serum vitamin A level reached 0.30 mg/L at the age of 9 years, and then an increasing trend with age was observed till 18 years. The median serum vitamin A level was higher in south area (male:0.33 mg/L; female:0.34 mg/L), compared with other areas (0.24-0.30 mg/L). The variation of the median serum vitamin A level among seasons was within 0.03 mg/L. Based on EM algorithm using indirect approach, the reference intervals of vitamin A for Chinese children and adolescents were as follows: newborn, 0.27-0.47 mg/L; infants aged below 1 year, 0.36-0.56 mg/L; children aged 1-<7 years, 0.35-0.54 mg/L; children aged 7-<16 years, 0.46-0.60 mg/L; and teenagers aged over 16 years, 0.38-0.59 mg/L. Conclusion: The EM algorithm can provide a basis for the establishment of vitamin A reference interval for Chinese children and adolescents, and the established reference interval needs to be further verified by direct method.