Objective: To establish comprehensive laboratory reference intervals for Chinese children. Methods: This was a cross-sectional multicenter study. From June 2013 to December 2014, eligible healthy children aged from 6-month to 17-year were enrolled from 20 medical centers with informed consent. They were assessed by physical examination, questionnaire survey and abdominal ultrasound for eligibility. Fasting blood samples were collected and delivered to central laboratory. Measurements of 15 clinical laboratory parameters were performed, including estradiol (E2), testosterone(T), luteinizing hormone(LH), follicle-stimulating hormone(FSH), alanine transaminase(ALT), serum creatinine(Scr), cystatin C, immunoglobulin A(IgA), immunoglobulin G(IgG), immunoglobulin M(IgM), complement (C3, C4), alkaline phosphatase(ALP), uric acid(UA) and creatine kinase(CK). Reference intervals were established according to central 95% confidence intervals for reference population, stratified by age and sex. Results: In total, 2 259 children were enrolled. Finally, 1 648 children were eligible for this study, including 830 boys and 818 girls, at a mean age of 7.4 years. Age- and sex- specific reference intervals have been established for the parameters. Reference intervals of sex hormones increased gradually with age. Concentrations of ALT, cystatin C, ALP and CK were higher in children under 2 years old. Serum levels of sex hormones, creatinine, immunoglobin, CK, ALP and urea increased rapidly in adolescence, with significant sex difference. In addition, reference intervals were variable depending on assay methods. Concentrations of ALT detected by reagents with pyridoxal 5'-phosphate(PLP) were higher than those detected by reagents without PLP. Compared with enzymatic method, Jaffe assay always got higher results of serum creatinine, especially in children younger than 9 years old. Conclusion: This study established age- and sex- specific reference intervals, for 15 clinical laboratory parameters based on defined healthy children.
目的： 建立不同年龄、性别儿童的临床常用检验指标的生物参考区间。 方法： 横断面多中心研究。由全国15个省、市（北京、广东、湖北、江苏、福建、陕西、山东、浙江、湖南、河南、天津、上海、重庆、四川、吉林）20家医学中心合作完成，自2013年6月至2014年12月招募6月龄~17岁的表观正常儿童作为研究对象，通过问卷调查、体格检查和腹部超声等筛选、建立"参考人群"；留取研究对象空腹血液标本，送中心实验室进行检测，检测指标包括性激素（雌二醇、睾酮、黄体生成素、卵泡刺激素，化学发光微粒子免疫检测法）、肝功能（丙氨酸转氨酶，加磷酸吡哆醛、不加磷酸吡哆醛试剂速率法两种方法同时检测）、肾功能（肌酐，碱性苦味酸法、酶法两种方法检测；胱抑素C，免疫透射比浊法）、免疫功能（免疫球蛋白A、免疫球蛋白G、免疫球蛋白M、补体C3、补体C4，免疫透射比浊法）、碱性磷酸酶（磷酸对硝基苯法）、尿酸（尿酸酶法）和肌酸激酶（酶法）。将"参考人群"上述15项指标的检测数据按照性别、年龄进行分层统计分析，建立中国儿童参考区间。 结果： 共招募2 259名儿童完成现场调查，筛选"表观正常儿童"1 648名作为"参考人群"；其中男830名、女818名，年龄（7.4±4.9）岁。建立了15项检验指标的生物参考区间，各指标参考区间随性别、年龄变化的趋势如下：（1）性激素：随年龄增长逐渐上升，卵泡刺激素在各年龄组均存在性别差异；（2）肝功能：2岁以下儿童的血丙氨酸转氨酶相对较高，5~9岁相对稳定，之后随年龄增长缓慢上升；（3）肾功能：儿童血肌酐随年龄增长持续上升，血胱抑素C在2岁以下相对高；（4）免疫功能：儿童血免疫球蛋白水平随年龄增长逐渐上升，而补体的参考范围相对恒定（年龄、性别差异不明显）；（5）其他：碱性磷酸酶和肌酸激酶在生后早期（2岁以下）处于较高水平，肌酸激酶和尿酸的检测值在5~9岁儿童相对稳定。上述指标中，性激素、肌酐、免疫球蛋白、肌酸激酶、碱性磷酸酶和尿酸的参考区间在进入青春期后迅速升高、伴有性别差异。检测丙氨酸转氨酶时，加磷酸吡哆醛试剂速率法的参考区间高于不加磷酸吡哆醛法；苦味酸法检测出的肌酐参考区间高于酶法（特别是9岁及以下儿童）。 结论： 建立了中国儿童基于年龄、性别分层的生物参考区间，涵盖肝肾功能、免疫功能和性激素等15项临床常用检验指标。.
Keywords: Child; Multicenter study; Reference interval.