Study On The Cutoff Value Of Serum Ferritin For Identifying Iron Deficiency

Iron deficiency (ID) is one of the worldwide nutritional disorders, which not only affects people’s health in the developing countries, but also is significantly prevalent in virtually all industrialized nations. ID happens in forms of three stages in order, which are iron deficient store (IDS), iron deficient erythropoiesis (IDE) and iron deficient anemia (IDA). During the first two stages, hemoglobin level of the body is within normal range and the symptoms of iron deficiency are not obvious although acturally ID has already happened, so these two stages are always called latent iron deficiency or sub-clinical iron deficiency. With the increase of people’s living level in our country, the incidence of IDA has considerably dropped, so at present the most important thing for preventing ID should be transferred to early detecting the subjects and populations with latent ID. Serum ferritin (SF) test is the only simple and feasible way to detect early iron deficiency. Its level decreases before iron deficient erythropoiesis and anemia happen, thus it is a biological indicator with relatively high sensitivity and specificity. During the recent three decades, many researchers domestic and abroad focused on the optimum cutoff value of SF for identifying ID but came with different results, and there is no unified diagnostic criterion of SF for ID in our country, so we carried out a series of studies on SF as an indicator for ID and its optimum cutoff value for identifying ID.1. Meta-analysis of studies on cutoff value of serum ferritin for identifying iron deficiencyObjective To systematically evaluate SF as the diagnostic standard for ID and discuss the appropriate cutoff value of SF for identifying iron deficiency. Methods A comprehensive electronic search and manual tracking was performed to collect potential studies on cutoff value of SF for identifying iron deficiency. Most relevant studies were identified according to the inclusion and exclusion criteria and data were extracted. MetaDisc1.4software was used to test the heterogeneity of the included studies and then proper efficacy models were selected for calculating pooled weighted diagnostic indicators and their95%CI. Summary receiver operating characteristic (SROC) curve was made and the area under the curve (AUC) and Q*index were calculated respectively for the three groups. Meta regression was performed to analyze the causes of heterogeneity and then subgroup analysis was made. Finally, sensitivity analysis were performed. Results A total of14studies were screened out from745studies and were divided into three groups according to the cutoff value of SF:12-20μg/L group,25,30μg/L group and36-60μg/L group. After the pooled efficacy analysis, we found that the12-20μg/L group showed the lowest pooled sensitivity [0.767,95%CI (0.705,0.821)] but highest specificity [0.959,95%CI (0.934,0.976)]. Compared with the other two groups, the pooled sensitivity of25,30μg/L group [0.877,95%CI (0.799,0.933)] was highest, its pooled specificity was0.944,95%CI (0.888,0.977), the pooled sensitivity and pooled specificity of30-60μg/L group [0.836,95%CI (0.797,0.870),0.876,95%CI (0.846,0.901)] were both relatively low. In terms of the integrated diagnostic capabilities, the25,30μg/L group showed the highest diagnostic odds ratio [101.42,95%CI (36.137,284.64)], the largest AUC (0.9497±0.039) and the Q*index nearest1(0.8901±0.052). The results of Meta regression showed that the method used to detect SF level and the anemia status of the subject are the two variables which were statistically significant. Subgroup analysis results indicated that for subjects without anemia, if the method of immunoradiometric assay was used to detect SF, the cutoff value of SF25μg/L was suggested; if microparticle enzyme immunoassay was used,60μg/L was suggested; for subjects with anemia, if immunoradiometric assay was used to detect SF,30μg/L was suggested; if method of ELISA was adopted,50μg/L was suggested, and if method of chemiluminescence was used, SF cutoff value of36μg/L was suggested. After we removed the studies with sample less than50and the studies by Chinese authors, the25,30μg/L group still showed the best diagnostic efficiency. Conclusion SF level of30μg/L may be the optimum cut-off value for identifying iron deficiency.2. Appropriateness assessment of serum ferritin<30μg/L for identifying iron deficiency in school age childrenObjective To evaluate the appropriateness of SF for identifying ID under the cutoff value of30μg/L which was concluded from the Meta analysis. Methods We conducted a cross-sectional survey aiming at the school age children in Beijing suburban area. The children’s Hb, SF,CRP and sTfR level were measured and sTfR/logSF, BIS were calculated. Incidence of ID was calculated and analyzed based on the criterion of SF<30μg/L and SF<15μg/L recommended by WHO, respectively. The differences of children’s body iron status between SF<30μg/L group and SF>30μg/L group were compared. The incidence of IDS, IDE, IDA and the ratio of latent iron deficiency to total iron deficiency were analyzed. We also analyzed the diagnostic agreement of SF<30μg/L and sTfR/logSF>1.5, SF<30μg/L and log sTfR:SF>2.55, SF<30μg/L and BIS<6mg/kg, respectively. Results A total of514subjects were recruited. The mean level of SF of all subjects was58.4±30.1μg/L (boys61.7±32.1μg/L, gilrs54.9±27.5μg/L),95%CI of SF was14.1-133.8μg/L. The incidence of ID was14.6%and2.7%based on the diagnostic criterion of SF<30μg/L and SF<15g/L. The differences between SF<30μg/L and SF>30μg/L of Hb、sTfR、sTfR/logSF and BIS were all statistically significant. The incidence of IDS, IDE, IDA was0.4%,13.8%,0.4%, respectively; the incidence of latent iron deficiency was14.2%and latent iron deficiency accounted for97.3%in total iron deficiency. The Kappa values of SF<30μg/L and sTfR/logSF>1.5, SF<30μg/L and log sTfR:SF>2.55, SF<30μg/L and BIS<6mg/kg were0.033,0.208,0.810,respectively. Conclusion SF level of30μg/L is appropriate for identifying iron deficiency in school age children.3. Study on cutoff value of serum ferritin for identifying iron deficiency in anemic populationsObjective To propose the optimum cutoff values of SF for identifying ID in high risk populations. Methods We recruited high risk populations of ID(children and adolescents, women of childbearing age, the elderly) to conduct a screening test on anemia. Subjects were identified according to the inclusion and exclusion criteria. Then, all subjects were asked to eat a pack of iron nutrition package every day for6months. Dietary survey, Hb, SF,CRP and sTfR measurement were performed for all subjects at the baseline, mid-time(3th month) and end-time(6th month),respectively. After the iron supplementation ended, all subjects were classified as ID or Non-ID according to whether he or she positively responded to iron intervention (his or her Hb level increased by lOg/L and more) during the first3month, then ROC method of diagnostic test was employed to analyze the best SF cutoff value for identifying ID for three populations. Results A total of74anemic children and adolescents(boys36, girls38),38anemic women of childbearing age and78old people with anemia (male40, female38) were identified as subjects. The results of dietary survey at baseline showed that the average intake of dietary iron of students was11.1±5.8mg/d, of women of childbearing age was9.9±5.5mg/d,of the elderly men was11.5±6.2mg/d, of the elderly women was9.0±5.9mg/d. During the first3month, the average intake of supplementary iron of boys was6.2mg/d, of girls was6.9mg/d, of women of childbearing age was7.3mg/d, of the elderly men was7.5mg/d and the elderly women was7.2mg/d. ROC analysis of diagnostic test showed the optimum cutoff value of SF for anemic boys was65μg/L, for anemic girls was60μg/L, if data of boys and girls were combined, it was60μg/L; for anemic women of childbearing age was40μg/L; for anemic elderly men was80μg/L, for anemic elderly women was60μg/L. Conclusion For populations with anemia, the recommended cutoff values of SF for identifying ID were as follows:children and adolescents:60μg/L; women of childbearing age:40μg/L; elderly women:60μg/L; elderly men:80μg/L.In this study, we focused on the optimum cutoff value of SF for identifying ID and carried out a series of studies by performing systematic review and Meta analysis and conducting cross-sectional survey and intervention study, so based on the data from both literatures and epidemic studies, the best cutoff value of SF for identifying ID was found, its appropriateness was evaluated and cutoff values for high risk populations were proposed. Study results of this research provide evidences for establishing criterion of SF identifying ID in our country, make it possible that we will find an accurate and feasible approach to assess iron status when doing epidemic survey, and also provide possible criteria for monitoring the effect of ID prevention and control.