Mwangi Martin N, Maskey Sumi, Andang o Pauline E A, Shinali Noel K, Roth Johanna M, Trijsburg Laura, Mwangi Alice M, Zuilhof Han, van Lagen Barend, Savelkoul Huub Fj, Demir Ayşe Y, Verhoef Hans
BMC Med. 2014 Nov 26;12:229. doi: 10.1186/s12916-014-0229-8.
Iron-deficient erythropoiesis results in excess formation of zinc protoporphyrin (ZPP), which can be measured instantly and at low assay cost using portable haematofluorometers. ZPP is used as a screening marker of iron deficiency in individual pregnant women and children, but also to assess population iron status in combination with haemoglobin concentration. We examined associations between ZPP and disorders that are common in Africa. In addition, we assessed the diagnostic utility of ZPP (measured in whole blood and erythrocytes), alone or in combination with haemoglobin concentration, in detecting iron deficiency (plasma ferritin concentration <15 μg/L).
Single blood samples were collected from a population sample of 470 rural Kenyan women with singleton pregnancies, gestational age 13 to 23 weeks, and haemoglobin concentration ≥90 g/L. We used linear regression analysis to assess associations between ZPP and iron markers (including anaemia), factors known or suspected to be associated with iron status, inflammation markers (plasma concentrations of C-reactive protein and α 1-acid glycoprotein), infections (Plasmodium infection, HIV infection), and other disorders (α(+)-thalassaemia, plasma concentrations of total bilirubin, and lactate dehydrogenase). Subsequently, in those without inflammation, Plasmodium infection, or HIV infection, we used logistic discriminant analysis and examined receiver operating characteristics curves with corresponding area-under-the-curve to assess diagnostic performance of ZPP, alone and in combination with haemoglobin concentration.
Individually, whole blood ZPP, erythrocyte ZPP, and erythrocyte protoporphyrin had limited ability to discriminate between women with and without iron deficiency. Combining each of these markers with haemoglobin concentration had no additional diagnostic value. Conventional cut off points for whole blood ZPP (>70 μmol/mol haem) resulted in gross overestimates of the prevalence of iron deficiency.
Erythrocyte ZPP has limited value to rule out iron deficiency when used for screening in conditions with a low prevalence (e.g., 10%). ZPP is of unreliable diagnostic utility when discriminating between pregnant women with and without iron deficiency. Based on these findings, guidelines on the use of ZPP to assess iron status in individuals or populations of pregnant women need review.
NCT01308112 (2 March 2011).
缺铁性红细胞生成会导致锌原卟啉(ZPP)过量生成,使用便携式血液荧光计可即时且低成本地测量ZPP。ZPP用作个体孕妇和儿童缺铁的筛查标志物,也可与血红蛋白浓度结合用于评估人群铁状态。我们研究了ZPP与非洲常见疾病之间的关联。此外,我们评估了ZPP(在全血和红细胞中测量)单独或与血红蛋白浓度联合检测缺铁(血浆铁蛋白浓度<15μg/L)的诊断效用。
从470名肯尼亚农村单胎妊娠妇女的人群样本中采集单份血样,这些妇女的孕周为13至23周,血红蛋白浓度≥90g/L。我们使用线性回归分析来评估ZPP与铁标志物(包括贫血)、已知或怀疑与铁状态相关的因素、炎症标志物(C反应蛋白和α1-酸性糖蛋白的血浆浓度)、感染(疟原虫感染、HIV感染)以及其他疾病(α(+)-地中海贫血、总胆红素血浆浓度和乳酸脱氢酶)之间的关联。随后,在那些没有炎症、疟原虫感染或HIV感染的人群中,我们使用逻辑判别分析并检查具有相应曲线下面积的受试者工作特征曲线,以评估ZPP单独及与血红蛋白浓度联合的诊断性能。
单独来看,全血ZPP、红细胞ZPP和红细胞原卟啉区分缺铁和不缺铁女性的能力有限。将这些标志物中的每一个与血红蛋白浓度相结合并没有额外的诊断价值。全血ZPP的传统截断点(>70μmol/mol血红素)导致对缺铁患病率的严重高估。
当用于低患病率(如10%)情况下的筛查时,红细胞ZPP排除缺铁的价值有限。在区分缺铁和不缺铁的孕妇时,ZPP的诊断效用不可靠。基于这些发现,关于使用ZPP评估个体或孕妇人群铁状态的指南需要重新审视。
NCT01308112(2011年3月2日)。