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Interpretation of serum ferritin concentrations as indicators of total-body iron stores in survey populations: the role of biomarkers for the acute phase response ^1,2,3,4

¹ From the Department of Nutritional Sciences, The Pennsylvania State University, University Park, PA (JLB, LEM-K, and FJR); CeSSIAM, Guatemala City, Guatemala (NWS); and the Department of Pediatrics, Wayne State University School of Medicine, Detroit, MI (MLA)

Background: Nutritional surveys use acute phase protein (APP) biomarkers such as C-reactive protein (CRP) and ₁-acid glycoprotein (AGP) to identify the influence of inflammation on the distribution of iron status biomarkers. Few, however, have examined which biomarker better identifies persons with spurious elevations in iron status markers.

Objective: We explored the relations of APP biomarkers to iron-status biomarkers in infants and school-age children.

Design: In screening surveys, we identified a sample of African American infants (n = 351) and Guatemalan school-age children (n = 375). We used a common set of APP and iron-status biomarkers to examine the association between the 2 sets of markers (laboratory variables).

Results: The overall prevalence of either inflammation or iron deficiency was <10% in both samples. The log AGP and CRP values were significantly correlated (r = 0.70), but the unexplained variance still was >50%. Serum ferritin—but not transferrin receptor, transferrin receptor index, or serum iron—was related to APP concentrations, but poor positive predictive value (<72%) and low kappa scores were found. Ferritin concentrations >1 geometric SD above the geometric mean were poorly predicted by either elevated AGP or CRP. Qualitative CRP analysis was not effective in identifying persons who had other indications of mild inflammation.

Conclusions: These analyses show that a low prevalence of inflammation has little influence on the distribution of ferritin, and 2 common indicators of inflammation do not perform equally well in identifying persons who may have elevations in ferritin due to inflammation.

Key Words: Iron deficiency • ferritin • transferrin receptor • acute phase proteins • C-reactive protein • ₁-acid glycoprotein • children • Guatemala

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