Selected laboratory-based biomarkers for assessing vitamin A deficiency in at-risk individuals.

IF 8.8 2区 医学 Q1 MEDICINE, GENERAL & INTERNAL
Bryan M Gannon, Samantha L Huey, Neel H Mehta, Nidhi Shrestha, Lucero Lopez-Perez, Ricardo X Martinez, Lisa M Rogers, Maria Nieves Garcia-Casal, Saurabh Mehta
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Currently, direct index measures and dose response biomarkers have been developed to provide assessments of vitamin A status.</p><p><strong>Objectives: </strong>To determine the accuracy of index tests routinely used as markers of subclinical vitamin A deficiency in individuals at risk for vitamin A deficiency. Secondary objectives are to assess covariates as sources of heterogeneity for the accuracy of index tests routinely used as markers of subclinical vitamin A deficiency.</p><p><strong>Search methods: </strong>We searched CENTRAL, MEDLINE, Embase, and six other databases up to 18 August 2022, without restriction (any sex, age, pregnancy status, breastfeeding status, physiological condition, living in any country).</p><p><strong>Selection criteria: </strong>We included any studies implementing concurrent measurement of at least one reference standard and one index test to measure vitamin A status. 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We stratified all analyses by the reference standard and cutoff used, and assessed the certainty of the evidence using GRADE.</p><p><strong>Main results: </strong>We included 40 studies reporting 65 records. None of the studies was designed as a diagnostic test accuracy (DTA) study, limiting our analyses and assessments. Index test performance was described by 25 studies for serum or plasma retinol (SR) versus retinol isotope dilution (RID), 16 studies for SR versus liver vitamin A, eight studies for retinol-binding protein (RBP) versus retinol isotope dilution (RID), three studies for RBP versus liver vitamin A, one study for breast milk vitamin A versus RID, three studies for relative dose response (RDR) versus RID, and four studies for RDR versus liver vitamin A. No studies evaluating modified RDR were eligible for inclusion. 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SR pooled sensitivity against liver vitamin A at the 0.1 μmol/g cutoff was 53% (95% CI 30 to 75; 16 studies, 192 participants; very low-certainty evidence) and specificity was 83% (95% CI 63 to 93; 16 studies, 370 participants; moderate-certainty evidence). SR pooled sensitivity against liver vitamin A at the 0.07 μmol/g cutoff was 54% (95% CI 33 to 74; 16 studies, 137 participants; very low-certainty evidence) and specificity was 79% (95% CI 57 to 91; 16 studies, 348 participants; moderate-certainty evidence). Retinol-binding protein for diagnosing vitamin A deficiency RBP pooled sensitivity against RID at the 0.1 μmol/g cutoff was 50% (95% CI 33 to 67; 8 studies, 30 participants; low-certainty evidence) and specificity was 76% (95% CI 72 to 81; 8 studies, 730 participants; moderate-certainty evidence). RBP pooled sensitivity against RID at the 0.07 μmol/g cutoff was 45% (95% CI 31 to 59; 8 studies, 47 participants; low-certainty evidence) and specificity was 77% (95% CI 71 to 82; 8 studies, 711 participants; moderate-certainty evidence). RBP pooled sensitivity against liver vitamin A at the 0.1 μmol/g cutoff was 0% (95% CI 0 to 100; 3 studies, 12 participants; very low-certainty evidence) and specificity was 98% (95% CI 84 to 100; 3 studies, 40 participants; very low-certainty evidence). RBP pooled sensitivity against liver vitamin A at the 0.07 μmol/g cutoff was 0% (95% CI 0 to 100; 3 studies, 9 participants; very low-certainty evidence) and specificity was 98% (95% CI 85 to 100; 3 studies, 43 participants; very low-certainty evidence) Relative dose response for diagnosing vitamin A deficiency RDR pooled sensitivity against RID at the 0.1 μmol/g and 0.07 μmol/g cutoffs were not estimable due to lack of true-positive and false-negative cases from three studies. 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Data assessing the accuracy of the breast milk vitamin A, RDR, and MRDR compared to reference standards, particularly in patients with vitamin A deficiency, are limited.</p>","PeriodicalId":10473,"journal":{"name":"Cochrane Database of Systematic Reviews","volume":"5 ","pages":"CD013742"},"PeriodicalIF":8.8000,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cochrane Database of Systematic Reviews","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/14651858.CD013742.pub2","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}
引用次数: 0

Abstract

Background: Vitamin A deficiency is a highly detrimental micronutrient deficiency associated with poor growth, impaired immune responses, increased incidence of disease, ocular impairments, and maternal and child mortality. Reliable diagnostic assessment of vitamin A status is crucial to inform its clinical management. Currently, direct index measures and dose response biomarkers have been developed to provide assessments of vitamin A status.

Objectives: To determine the accuracy of index tests routinely used as markers of subclinical vitamin A deficiency in individuals at risk for vitamin A deficiency. Secondary objectives are to assess covariates as sources of heterogeneity for the accuracy of index tests routinely used as markers of subclinical vitamin A deficiency.

Search methods: We searched CENTRAL, MEDLINE, Embase, and six other databases up to 18 August 2022, without restriction (any sex, age, pregnancy status, breastfeeding status, physiological condition, living in any country).

Selection criteria: We included any studies implementing concurrent measurement of at least one reference standard and one index test to measure vitamin A status. Eligible studies included cross-sectional or cohort-accuracy studies; longitudinal studies; and direct, indirect, and random comparison studies, in which multiple index tests with a reference standard were evaluated. Interventional studies measuring vitamin A status following supplementation or intervention were also included, while case-control studies defining cases by vitamin A status were excluded.

Data collection and analysis: Two review authors independently screened studies and extracted data. We evaluated the methodological quality, that is, risk of bias of included studies and their applicability by using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. When meta-analysis was appropriate, we used random-effects bivariate models to obtain pooled estimates of sensitivity and specificity. We stratified all analyses by the reference standard and cutoff used, and assessed the certainty of the evidence using GRADE.

Main results: We included 40 studies reporting 65 records. None of the studies was designed as a diagnostic test accuracy (DTA) study, limiting our analyses and assessments. Index test performance was described by 25 studies for serum or plasma retinol (SR) versus retinol isotope dilution (RID), 16 studies for SR versus liver vitamin A, eight studies for retinol-binding protein (RBP) versus retinol isotope dilution (RID), three studies for RBP versus liver vitamin A, one study for breast milk vitamin A versus RID, three studies for relative dose response (RDR) versus RID, and four studies for RDR versus liver vitamin A. No studies evaluating modified RDR were eligible for inclusion. Specificity data were available from all studies; sensitivity was often estimable from only a portion of studies due to some studies having no condition-positive cases according to the reference standard (zero true positive and false negative cases). One comparison, RDR versus RID, yielded no sensitivity data, therefore we could evaluate only pooled specificity data. We generally judged risk of bias as 'unclear' across studies. Serum or plasma retinol for diagnosing vitamin A deficiency SR pooled sensitivity against RID at the 0.1 μmol/g cutoff was 10% (95% confidence interval (CI) 2 to 38; 23 studies, 385 participants; very low-certainty evidence), and specificity was 92% (95% CI 85 to 96; 23 studies, 1110 participants; low-certainty evidence). SR pooled sensitivity against RID at the 0.07 μmol/g cutoff was 13% (95% CI 4 to 34; 24 studies, 246 participants; very low-certainty evidence), and specificity was 94% (95% CI 87 to 97, 24 studies, 1295 participants; low-certainty evidence). SR pooled sensitivity against liver vitamin A at the 0.1 μmol/g cutoff was 53% (95% CI 30 to 75; 16 studies, 192 participants; very low-certainty evidence) and specificity was 83% (95% CI 63 to 93; 16 studies, 370 participants; moderate-certainty evidence). SR pooled sensitivity against liver vitamin A at the 0.07 μmol/g cutoff was 54% (95% CI 33 to 74; 16 studies, 137 participants; very low-certainty evidence) and specificity was 79% (95% CI 57 to 91; 16 studies, 348 participants; moderate-certainty evidence). Retinol-binding protein for diagnosing vitamin A deficiency RBP pooled sensitivity against RID at the 0.1 μmol/g cutoff was 50% (95% CI 33 to 67; 8 studies, 30 participants; low-certainty evidence) and specificity was 76% (95% CI 72 to 81; 8 studies, 730 participants; moderate-certainty evidence). RBP pooled sensitivity against RID at the 0.07 μmol/g cutoff was 45% (95% CI 31 to 59; 8 studies, 47 participants; low-certainty evidence) and specificity was 77% (95% CI 71 to 82; 8 studies, 711 participants; moderate-certainty evidence). RBP pooled sensitivity against liver vitamin A at the 0.1 μmol/g cutoff was 0% (95% CI 0 to 100; 3 studies, 12 participants; very low-certainty evidence) and specificity was 98% (95% CI 84 to 100; 3 studies, 40 participants; very low-certainty evidence). RBP pooled sensitivity against liver vitamin A at the 0.07 μmol/g cutoff was 0% (95% CI 0 to 100; 3 studies, 9 participants; very low-certainty evidence) and specificity was 98% (95% CI 85 to 100; 3 studies, 43 participants; very low-certainty evidence) Relative dose response for diagnosing vitamin A deficiency RDR pooled sensitivity against RID at the 0.1 μmol/g and 0.07 μmol/g cutoffs were not estimable due to lack of true-positive and false-negative cases from three studies. RDR pooled specificity against RID at the 0.1 μmol/g cutoff was 89% (95% CI 26 to 99; 3 studies, 34 participants; low-certainty evidence), and RDR pooled specificity against RID at the 0.07 μmol/g cutoff was 91% (95% CI 54 to 99; 3 studies, 34 participants; low-certainty evidence).

Authors' conclusions: Available data indicate that methods to determine vitamin A deficiency had generally low sensitivity, when estimable (0% to 54%), and generally high specificity (74% to 94%) in individuals at risk for vitamin A deficiency. Estimates should be interpreted with caution because no included studies were designed or conducted as DTA studies. Data assessing the accuracy of the breast milk vitamin A, RDR, and MRDR compared to reference standards, particularly in patients with vitamin A deficiency, are limited.

用于评估高危人群维生素A缺乏症的实验室生物标志物。
背景:维生素A缺乏症是一种非常有害的微量营养素缺乏症,与生长不良、免疫反应受损、疾病发病率增加、视力损害以及孕产妇和儿童死亡率有关。维生素A状态的可靠诊断评估对其临床管理至关重要。目前,已经开发了直接指数测量和剂量反应生物标志物来评估维生素A的状态。目的:确定在有维生素A缺乏风险的个体中作为亚临床维生素A缺乏标记物的指标测试的准确性。次要目的是评估协变量作为亚临床维生素A缺乏症指标测试准确性的异质性来源。检索方法:截至2022年8月18日,我们检索了CENTRAL、MEDLINE、Embase和其他6个数据库,没有任何限制(任何性别、年龄、妊娠状况、母乳喂养状况、生理状况、居住在任何国家)。选择标准:我们纳入了同时测量至少一种参考标准和一种指数测试来测量维生素A状态的所有研究。符合条件的研究包括横断面或队列准确性研究;纵向研究;以及直接、间接和随机比较研究,其中对具有参考标准的多个指标测试进行评估。测量补充或干预后维生素A水平的介入研究也包括在内,而通过维生素A水平定义病例的病例对照研究被排除在外。数据收集和分析:两位综述作者独立筛选研究并提取数据。我们使用诊断准确性研究质量评估(QUADAS-2)工具评估方法学质量,即纳入研究的偏倚风险及其适用性。当荟萃分析合适时,我们使用随机效应双变量模型来获得敏感性和特异性的汇总估计。我们通过参考标准和截止值对所有分析进行分层,并使用GRADE评估证据的确定性。主要结果:我们纳入了40项研究,报告了65例记录。没有一项研究被设计为诊断测试准确性(DTA)研究,限制了我们的分析和评估。指标试验性能由25项血清或血浆视黄醇(SR)与视黄醇同位素稀释(RID)的研究、16项SR与肝脏维生素A的研究、8项视黄醇结合蛋白(RBP)与视黄醇同位素稀释(RID)的研究、3项RBP与肝脏维生素A的研究、1项母乳维生素A与RID的研究、3项相对剂量反应(RDR)与RID的研究描述。以及4项RDR与肝脏维生素a的研究。没有评估改良RDR的研究符合纳入条件。所有研究均有特异性数据;由于一些研究根据参考标准没有条件阳性病例(零真阳性和假阴性病例),因此往往只能从一部分研究中估计灵敏度。RDR与RID的一项比较没有获得敏感性数据,因此我们只能评估合并的特异性数据。在所有研究中,我们通常将偏倚风险判断为“不清楚”。血清或血浆视黄醇诊断维生素A缺乏症在0.1 μmol/g临界值下对RID的综合敏感性为10%(95%可信区间(CI) 2 ~ 38;23项研究,385名参与者;极低确定性证据),特异性为92% (95% CI 85 ~ 96;23项研究,1110名参与者;确定性的证据)。在0.07 μmol/g截止点,SR对RID的综合敏感性为13% (95% CI 4 ~ 34;24项研究,246名参与者;极低确定性证据),特异性为94% (95% CI 87 ~ 97,24项研究,1295名受试者;确定性的证据)。在0.1 μmol/g临界值下,SR对肝脏维生素A的综合敏感性为53% (95% CI 30 ~ 75;16项研究,192名参与者;非常低确定性证据),特异性为83% (95% CI 63 ~ 93;16项研究,370名参与者;moderate-certainty证据)。在0.07 μmol/g临界值下,SR对肝脏维生素A的总敏感性为54% (95% CI 33 ~ 74;16项研究,137名参与者;非常低确定性证据),特异性为79% (95% CI 57 - 91;16项研究,348名参与者;moderate-certainty证据)。视黄醇结合蛋白诊断维生素A缺乏症的RBP在0.1 μmol/g临界值下对RID的总敏感性为50% (95% CI 33 ~ 67;8项研究,30名参与者;低确定性证据),特异性为76% (95% CI 72 ~ 81;8项研究,730名参与者;moderate-certainty证据)。在0.07 μmol/g临界值下,RBP对RID的综合敏感性为45% (95% CI 31 ~ 59;8项研究,47名参与者;低确定性证据),特异性为77% (95% CI 71 ~ 82;8项研究,711名参与者;moderate-certainty证据)。RBP对肝脏维生素A的敏感性在0。 1 μmol/g临界值为0% (95% CI 0 ~ 100;3项研究,12名受试者;极低确定性证据),特异性为98% (95% CI 84 - 100;3项研究,40名参与者;非常低确定性证据)。在0.07 μmol/g临界值下,RBP对肝脏维生素A的综合敏感性为0% (95% CI 0 ~ 100;3项研究,9名受试者;极低确定性证据),特异性为98% (95% CI 85至100;3项研究,43名参与者;在0.1 μmol/g和0.07 μmol/g临界值下,由于缺少三个研究的真阳性和假阴性病例,因此无法估计RDR对RID的综合敏感性。在0.1 μmol/g临界值下,RDR对RID的合并特异性为89% (95% CI 26 ~ 99;3项研究,34名受试者;低确定性证据),RDR在0.07 μmol/g临界值下对RID的特异性为91% (95% CI 54 ~ 99;3项研究,34名受试者;确定性的证据)。作者的结论:现有数据表明,测定维生素A缺乏症的方法在可估计时通常灵敏度较低(0%至54%),而在维生素A缺乏症风险个体中通常具有高特异性(74%至94%)。由于没有纳入的研究被设计或进行为DTA研究,因此应谨慎解释估计。与参考标准相比,评估母乳维生素A、RDR和MRDR准确性的数据是有限的,特别是在维生素A缺乏症患者中。
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来源期刊
CiteScore
10.60
自引率
2.40%
发文量
173
审稿时长
1-2 weeks
期刊介绍: The Cochrane Database of Systematic Reviews (CDSR) stands as the premier database for systematic reviews in healthcare. It comprises Cochrane Reviews, along with protocols for these reviews, editorials, and supplements. Owned and operated by Cochrane, a worldwide independent network of healthcare stakeholders, the CDSR (ISSN 1469-493X) encompasses a broad spectrum of health-related topics, including health services.
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