目的 评估应用末梢全血干血斑(DBS)诊断边缘性维生素A(VA)缺乏(MVAD)的可靠性,为临床科学评估VA营养状况提供参考依据。方法 2018年选择130名赵县地区2~7岁儿童,采集末梢全血制备干血斑,其中48名儿童同时采集静脉血浆。采用超高效液相色谱-串联质谱法(HPLC-MS/MS)检测两种生物基质中视黄醇水平。应用两种校正方法将干血斑视黄醇转化为其同源血浆中视黄醇水平。采用组内相关系数(ICC)和Bland-Altman评估转换后视黄醇水平与血浆视黄醇水平的一致性。应用敏感性、特异性、准确性指数(AI)、阳性预测值(PPV)和阴性预测值(NPV)评估DBS诊断MVAD的可靠性。结果 DBS视黄醇经两种方法校正后与同源血浆中水平一致性良好,ICC值均大于0.8,其中系数校正后的等效血浆视黄醇更接近血浆真实值。应用系数校正后DBS视黄醇分析目标人群MVAD患病率为45.00%,与血浆视黄醇诊断的MVAD患病率一致(45.83%),系数校正后DBS视黄醇诊断MVAD的灵敏度及特异性分别为77.78%,81.82%,AI为80.00%,PPV为77.78%,NPV为81.82%。赵县130例2~7岁儿童VAD及MVAD患病率为3.08%,45.38%,大年龄组(5~7岁)儿童有更高的MVAD患病风险(51.22%,t=1.975,P=0.359)。结论 DBS视黄醇经系数校正后可用于MVAD的诊断。赵县2~7岁儿童MVAD比例较高,应及时增补并加强监测。
Abstract
Objective To assess the reliability and validity of dried blood spot(DBS) in the diagnosis of marginal vitamin A deficiency(MVAD) in preschoolers, in order to provide reference for scientifically assessing vitamin A nutritional status. Methods A total of 130 children aged 2 to 7 years were selected in the Zhao county in 2018 and their capillary bloods were collected to prepare DBS, of whom 48 children also collected venous plasma at the same time. The retinol levels in the 2 biological matrices were measured using high-performance liquid chromatography-tandem mass spectrometry method(HPLC-MS/MS). Two calibration methods were applied to convert DBS retinol to its homologous plasma retinol level. The agreement of the converted retinol with plasma retinol level was assessed using the intra-group correlation coefficient(ICC) and Bland-Altman analysis. The validity for the diagnosis of MVAD was assessed by sensitivity, specificity, accuracy index(AI), positive predictive value(PPV) and negative predictive value(NPV). Results After correction, DBS retinol was in good agreement with the level in homologous plasma, with ICC values greater than 0.8. Factor-corrected DBS retinol was closer to its plasma level. The prevalence of MVAD in the target population diagnosed by factor-corrected DBS retinol was 45.00%, which was close to the prevalence of MVAD diagnosed by plasma retinol(45.83%). The sensitivity, specificity, AI, PPV and NPV of factor-corrected DBS retinol predicting MVAD were 77.78%, 81.82%, 80.00%, 77.78% and 81.82%, respectively. The prevalence rates of VAD and MVAD in 130 children aged 2 to 7 years in Zhao county were 3.08% and 45.38%, respectively. Children aged 5 to 7 years had a higher prevalence rate of MVAD(51.22%, t=1.975, P=0.359). Conclusion Corrected DBS retinol can be used in the diagnosis of MVAD and the prevalence rate of MVAD is high in preschoolers in Zhao county.
关键词
干血斑 /
视黄醇 /
维生素A营养状况评估 /
学龄前儿童 /
灵敏度 /
特异性
Key words
dried blood spot /
retinol /
vitamin A nutritional status assessment /
preschooler /
sensitivity /
specificity
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基金
国家自然科学基金青年项目(81400848);北京市属医院科研培育计划(PX2019051);首都儿科研究所所级基金(PY-2020-10)