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.
目的： 间接法建立我国儿童青少年维生素A参考区间。 方法： 采用现况研究设计，利用临床检验真实世界数据，数据来源于2016年1月至2019年6月28个省、自治区、直辖市某第三方临床检测机构的维生素A检测结果，采用高效液相色谱法完成血清视黄醇样品测定。对0~18周岁儿童青少年血清维生素A水平在人群、地区、季节方面的分布进行描述性统计，采用期望最大化（EM）算法迭代计算维生素A水平分布参数，并建立参考区间。 结果： 共1 096 597名0~18岁儿童青少年个案数据纳入分析，年龄［M（Q1，Q3）］3（1，6）岁，男631 017名，女性465 580名。4岁前血清维生素A水平［M（Q1，Q3）］随年龄增加，新生儿中位数和四分位数为0.15（0.11，0.18）mg/L，1岁以内为0.23（0.18，0.29）mg/L，1~<4岁为0.27（0.20，0.34）mg/L，4~8岁中位数水平较平稳，为0.27~0.29 mg/L，9岁左右中位数水平达到0.30 mg/L，之后至18岁呈现随年龄增加趋势（不同性别均Ptrend<0.05）。不同地区间，华南地区维生素A中位数水平（男性0.33 mg/L，女性0.34 mg/L）高于其他地区（0.24~0.30 mg/L）；不同季节间维生素A中位数差异在0.03 mg/L以内。基于EM算法采用间接法建立的我国0~18岁儿童青少年维生素A参考区间为：新生儿0.27~0.47 mg/L，1岁以内0.36~0.56 mg/L，1~<7岁0.35~0.54 mg/L，7~<16岁0.46~0.60 mg/L，16岁及以上0.38~0.59 mg/L。 结论： 基于EM算法能够为建立我国0~18岁儿童青少年维生素A参考区间提供依据，建立的参考区间需要通过直接法进一步验证。.