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Published on: January 19, 2024
Comparison of indicators of iron deficiency in Kenyan children
Frederick K E Grant1, Reynaldo Martorell, Rafael Flores-Ayala
1Nutrition and Health Sciences program of Graduate Division of Biological and Biomedical Sciences, Emory University, Atlanta, GA 30322, USA. ebogrant5@yahoo.com
Insights
Soluble transferrin receptor (TfR) is the most accurate single biomarker for screening iron deficiency (ID) in young children, outperforming ferritin and zinc protoporphyrin (ZP) in resource-poor settings.
Area of Science:
- Nutritional Biochemistry
- Pediatric Health
- Public Health Screening
Background:
- Iron deficiency (ID) diagnosis lacks a noninvasive gold standard, necessitating multiple indicators.
- Selecting a single biomarker for population-level ID screening remains debated.
Purpose of the Study:
- To compare a multiple-criteria model for ID with individual iron biomarkers (ferritin, TfR, ZP) and the TfR/ferritin index.
- To evaluate biomarker performance with and without adjustment for inflammation.
Main Methods:
- Community-based cluster survey of 680 children (6-35 months).
- Measured iron status using ferritin, TfR, and ZP.
- Compared ID definitions (multiple-criteria vs. single biomarkers) with and without inflammation adjustment.
Main Results:
- Soluble transferrin receptor (TfR) showed the best agreement (κ = 0.88) with the multiple-criteria ID model.
- TfR demonstrated superior diagnostic accuracy (AUC = 0.94) compared to other indicators.
- Inflammation adjustment minimally impacted the observed results.
Conclusions:
- TfR is a more reliable single indicator for estimating ID prevalence in preschoolers than ferritin, ZP, or the TfR/ferritin index.
- Findings are significant for high-inflammation, resource-poor settings.
- Trial registered at clinicaltrials.gov (NCT101088958).
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 microg/L), soluble transferrin receptor (TfR; > 8.3 mg/L), or zinc protoporphyrin (ZP; > 80 micromol/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.
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