Comparison of indicators of iron deficiency in Kenyan children

Abstract

Background: In the absence of a feasible, noninvasive gold standard, iron deficiency (ID) is best measured by the use of multiple indicators. However, the choice of an appropriate single iron biomarker to replace the multiple-criteria model for screening for ID at the population level continues to be debated.

Objective: We compared ID defined as ≥ 2 of 3 abnormal ferritin (< 12 μg/L), soluble transferrin receptor (TfR; > 8.3 mg/L), or zinc protoporphyrin (ZP; > 80 μmol/mol) concentrations (ie, multiple-criteria model) with ID defined by abnormal concentrations of any of the independent candidate iron biomarkers (ferritin alone, TfR alone, or ZP alone) and TfR/ferritin index (ID, > 500). Values either were adjusted for inflammation [as measured by C-reactive protein (> 5 mg/L) and α(1)-acid glycoprotein (> 1 g/L) before applying cutoffs for ID] or were unadjusted.

Design: In this community-based cluster survey, capillary blood was obtained from 680 children (aged 6-35 mo) for measurement of iron status by using ferritin, TfR, and ZP.

Results: On the basis of the multiple-criteria model, the mean (±SE) prevalence of ID was 61.9 ± 2.2%, whereas the prevalences based on abnormal ferritin, TfR, or ZP concentrations or an abnormal TfR/ferritin index were 26.9 ± 1.7%, 60.9 ± 2.2%, 82.8 ± 1.6%, and 43.1 ± 2.3%, respectively, for unadjusted values. The prevalences of ID were higher for adjusted values only for low ferritin and an elevated TfR/ferritin index compared with the unadjusted values. The κ statistics for agreement between the multiple-criteria model and the other iron indicators ranged from 0.35 to 0.88; TfR had the best agreement (κ = 0.88) with the multiple-criteria model. Positive predictive values of ID based on the other iron indicators in predicting ID based on the multiple-criteria model were highest for ferritin and TfR. Receiver operating characteristic curve analysis indicated that TfR (AUC = 0.94) was superior to the other indicators in diagnosing ID based on the multiple-criteria model (P < 0.001). The inflammation effect did not appear to alter these observations appreciably.

Conclusion: TfR better estimates the prevalence of ID in preschoolers than do ferritin, ZP, and the TfR/ferritin index on the basis of multiple indexes in a high inflammation, resource-poor setting. This trial was registered at clinicaltrials.gov as NCT101088958.

Trial registration: ClinicalTrials.gov NCT01088958.

FIGURE 1

ROC curve analysis for the diagnosis of ID (based on the multiple-criteria model) by using the TfR/ferritin index and 3 different independent tests in a sample of Kenyan children aged 6–35 mo. ID was defined per the multiple-criteria model as ≥2 abnormal values from among ferritin (<12 μg/L), TfR (>8.3 mg/L), and ZP (>80 μmol/mol) (13, 14). AUC values (and 95% CIs) for low ferritin (<12 μg/L), elevated TfR (>8.3 mg/L), elevated ZP (>80 μmol/mol), and an elevated TfR/ferritin index (>500) were as follows: 0.704 (0.679, 0.729), 0.942 (0.923, 0.960), 0.717 (0.686, 0.747), and 0.757 (0.727, 0.787), respectively. TfR was the most accurate estimator of ID (P < 0.0001; n = 679). ID, iron deficiency; ROC, receiver operating characteristic; TfR, plasma soluble transferrin receptor; TfR/SF index, ratio of plasma soluble transferrin receptor to plasma ferritin index; ZP, whole-blood zinc protoporphyrin.