基于多中心研究建立儿童微量血维生素D质谱法检测的临床应用标准  

Standardization of clinical application of mass spectrometry method for measurement of vitamin D in capillary blood of children:a multicenter study

作　　者：李娈娈 李晓南[2] 贾飞勇[3] 池美珠[4] 温志红[5] 杨凡[6] 李宇宁[7] 哈丽君 杨颖 龙晓玲[10] 方拴锋 谢露[12] 张会丰[13] 余晓丹 Li Luanluan;Li Xiaonan;Jia Feiyong;Chi Meizhu;Wen Zhihong;Yang Fan;Li Yuning;Ha Lijun;Yang Ying;Long Xiaoling;Fang Shuanfeng;Xie Lu;Zhang Huifeng;Yu Xiaodan(Department of Developmental and Behavioral Pediatrics,Shanghai Children′s Medical Center,Shanghai Jiao Tong University School of Medicine,Shanghai 200127,China;Department of Child Health Care,Children′s Hospital of Nanjing Medical University,Nanjing 210008,China;Department of Developmental and Behavioral Pediatrics,the First Hospital of Jilin University,Changchun 130021,China;Department of Child Health Care,the First Hospital of Wenzhou Medical University,Wenzhou 325000,China;Department of Pediatrics,the People′s Hospital of Guangxi Zhuang Autonomous Region,Nanning 530021,China;Department of Child Health Care,West China Second University Hospital,Sichuan University,Chengdu 610041,China;Department of Pediatrics,the First Hospital of Lanzhou University,Lanzhou 730013,China;Department of Child Health Care,Yinchuan Maternity and Child Health Care Hospital,Yinchuan 750000,China;Department of Child Health Care and Neurological Rehabilitation,Sports Center Branch of Dalian Municipal Women and Children′s Medical Center(Group),Dalian 116033,China;Department of Pediatrics,Boai Hospital of Zhongshan,Zhongshan 528405,China;Department of Child Health Care,Children′s Hospital of Zhengzhou University,Zhengzhou 450007,China;Department of Pediatrics,Kunming Maternity and Child Health Care Hospital,Kunming 650031,China;Department of Pediatrics,the Second Hospital of Hebei Medical University,Shijiazhuang 050000,China)

机构地区：[1]上海交通大学医学院附属上海儿童医学中心发育行为儿科,上海200127 [2]南京医科大学附属儿童医院儿童保健科,南京210008 [3]吉林大学第一医院发育行为儿科,长春130021 [4]温州医科大学附属第一医院儿童保健科,温州325000 [5]广西壮族自治区人民医院儿科,南宁530021 [6]四川大学华西第二医院儿童保健科,成都610041 [7]兰州大学第一医院儿科,兰州730013 [8]银川市妇幼保健院儿童保健科,银川750000 [9]大连市妇女儿童医疗中心(集团)体育新城院区儿童保健神经康复科,大连116033 [10]中山市博爱医院儿科,中山528405 [11]郑州大学附属儿童医院儿童保健科,郑州450007 [12]昆明市妇幼保健院儿科,昆明650031 [13]河北医科大学第二医院儿科,石家庄050000

出　　处：《中华儿科杂志》2022年第12期1282-1287,共6页Chinese Journal of Pediatrics

基　　金：中国妇幼保健协会妇儿健康临床标准与规范化项目(ZGFY-B-201904)。

摘　　要：目的建立末梢微量血维生素D质谱法检测规范和临床应用标准。方法横断面研究,根据地域分布,按照“省-市-医院”的技术抽样路线,于2020年11月至2021年12月抽取来自12个省、自治区、直辖市的1655名7岁以下健康儿童为研究对象。采集同一对象的静脉血和末梢微量血,应用高效液相色谱-串联质谱法分别检测两种样本的血清25(OH)D水平。采用Pearson相关性分析和线性回归分析探讨两种样本25(OH)D的相关性及转换公式。采用Bland-Altman法、Kappa分析法和受试者工作特征(ROC)曲线法进行一致性检验及灵敏度和特异度评价。结果1655名7岁以下儿童静脉血25(OH)D水平为74.25(59.50,92.00)nmol/L,微量血25(OH)D水平为68.75(54.44,86.25)nmol/L,差异有统计学意义(Z=22.14,P<0.001),且两者存在相关性(r=0.95,P<0.001)。进一步线性回归分析得到转换公式:lg[校正微量血25(OH)D]=0.13+0.95×lg[微量血25(OH)D](R^(2)=0.90,P<0.001)。校正微量血25(OH)D和静脉血25(OH)D的差值为(0.50±17.50)nmol/L,差异无统计学意义(P>0.05),且两者在临床诊断的一致性较好(Kappa值0.68~0.81)。静脉血25(OH)D临床界值30.00、50.00、75.00 nmol/L对应的微量血切点值分别为26.59、45.56、69.84 nmol/L。校正微量血25(OH)D临床预判价值较高(曲线下面积为0.97~0.99,灵敏度0.72~0.92,特异度0.89~0.99)。结论经过标化的微量血质谱法可用于临床上儿童维生素D检测。Objective To establish the norms and clinical application standards of mass spectrometry method to measure vitamin D in capillary blood.Methods Following the"Province-City-Hospital"sampling procedure,a cross-sectional sample of 1655 healthy children under 7 years of age were recruited from 12 provinces,autonomous regions,or municipalities in China from November 2020 to December 2021.Both venous and capillary blood samples from the same individual were collected,for which serum 25(OH)D levels were measured by high-performance liquid chromatography-mass spectrometry(HPLC-MS/MS)method.Pearson correlation analysis and linear regression analysis were used to detect the correlation and determine a correction algorithm.The agreement was analyzed using Bland-Altman plot and Kappa statistic.The sensitivity and specificity were evaluated using receiver operating characteristic(ROC)curve method.Results Venous and capillary 25(OH)D levels of 1655 healthy children under 7 years of age were 74.25(59.50,92.00)and 68.75(54.44,86.25)nmol/L,respectively,showed a significant difference(Z=22.14,P<0.001)as well as a highly significant correlation between venous and capillary 25(OH)D levels(r=0.95,P<0.001).Linear regression analysis was then performed to determine the correction algorithm:lg(corrected capillary 25(OH)D)=0.13+0.95×lg(capillary 25(OH)D)(R2=0.90,P<0.001).The deviation between venous and corrected capillary 25(OH)D levels was(0.50±17.50)nmol/L,a difference value that did not reach statistical significance(P>0.05).The cut-off values of capillary blood 25(OH)D values 30.00,50.00,75.00 nmol/L corresponding to venous blood 25(OH)D values were 26.59,45.56,and 69.84 nmol/L,respectively.Good consistency was observed between venous and corrected capillary 25(OH)D levels in clinical diagnosis(Kappa value 0.68-0.81).Corrected capillary 25(OH)D showed a high clinically predictive value(area under curve 0.97-0.99,sensitivity 0.72-0.92,specificity 0.89-0.99).Conclusion The standardized capillary HPLC-MS/MS method can be used to dete

关 键 词：儿童 维生素D 微量血 串联质谱法 标准化 

分 类 号：O657.63[理学—分析化学] R446.11[理学—化学]