The Journal of Nutrition
Community and International Nutrition
Correcting for Inflammation Changes Estimates
of Iron Deficiency among Rural Kenyan
Frederick K. E. Grant,4,6* Parminder S. Suchdev,4–7Rafael Flores-Ayala,6,7Conrad R. Cole,8
Usha Ramakrishnan,4,6Laird J. Ruth,7and Reynaldo Martorell4,6
4Nutrition and Health Sciences Program, Graduate Division of Biological and Biomedical Sciences,5Department of Pediatrics, School of
Medicine, and6Hubert Department of Global Health of the Rollins School of Public Health, Emory University, Atlanta, GA;7Centers for
Disease Control and Prevention, Atlanta, GA; and8Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children’s
Hospital Medical Center, Cincinnati, OH
The assessment of iron status where infections are common is complicated by the effects of inflammation on iron
indicators and in this study we compared approaches that adjust for this influence. Blood was collected in 680 children
(aged 6–35 mo) and indicators of iron status [(hemoglobin (Hb), zinc protoporphyrin (ZP), ferritin, transferrin receptor (TfR),
and TfR/ferritin index)] and subclinical inflammation [(the acute phase proteins (APP) C-reactive protein (CRP), and a-1-acid
glycoprotein (AGP)] were determined. Malaria parasitemia was assessed. Subclinical inflammation was defined as CRP
.5 mg/L and/orAGP .1 g/L). Four groups weredefined basedon APP levels: reference (normalCRP and AGP),incubation
(raised CRP and normal AGP), early convalescence (raised CRP and AGP), and late convalescence (normal CRP and raised
AGP). Correction factors (CF) were estimated as the ratios of geometric means of iron indicators to the reference group of
those for each inflammation group. Corrected values of iron indicators within inflammation groups were obtained by
multiplying values by their respective group CF. CRP correlated with AGP (r = 0.65; P , 0.001), ferritin (r = 0.38; P ,
0.001), Hb (r = 20.27; P , 0.001), and ZP (r = 0.16; P , 0.001); AGP was correlated with ferritin (r = 0.39; P , 0.001), Hb
(r = 20.29; P , 0.001), and ZP (r = 0.24; P , 0.001). Use of CF to adjust for inflammation increased the prevalence of ID
based on ferritin , 12 mg/L by 34% (from 27 to 41%). Applying the CF strengthened the expected relationship between
Hb and ferritin (r = 0.10; P = 0.013 vs. r = 0.20; P , 0.001, before and after adjustment, respectively). Although the use of
CF to adjust for inflammation appears indicated, further work is needed to confirm that this approach improves the
accuracy of assessment of ID.J. Nutr. 142: 105–111, 2012.
The WHO/CDC consultative group recommends that in addi-
tion to Hb9, the concentrations of ferritin, and TfR should be
measured in the assessment of ID (1). Additionally, ZP, a
measure of bone marrow iron availability for erythropoiesis, is
useful in identifying preanemic ID (2,3).
The assessment of the true burden of ID is complicated by the
influence of infections, such as malaria and HIV, on iron
indicators, especially in developing countries (4). This makes ID
monitoring among children in these areas difficult, because
inflammation influences Hb, ferritin, ZP, and to a lesser extent
TfR (5,6). The serum ferritin concentration, an indicator of iron
body stores, spikes during inflammations, even in the case of
subclinical inflammation whose occurrence is reflected in
elevated APP, namely CRP and AGP; this makes interpretation
of iron status problematic (4). CRP levels increase within 10 h of
the onset of acute inflammation and normalize rapidly, usually
within 1 wk (6), whereas AGP levels begin to increase 24 h after
the onset of inflammation but remain elevated well into
convalescence (4). Levels of CRP and AGP may thus identify
different but overlapping groups of people with respect to their
inflammation status (6). Inflammation has a smaller influence on
plasma TfR (an indicator of erythropoietic intensity and iron
requirements) compared to its influence on ferritin (7,8).
Therefore, TfR may be useful when estimating the prevalence
of ID in the presence of inflammation. Thus, in areas of
high inflammation burden such as in developing countries, the
1Supported in part by an Ellison Medical Foundation/Nevin Scrimshaw
International Nutrition Foundation fellowship (F.K.E.G.) and the CDC (P.S.S.).
The findings and conclusions in this report are those of the authors and do not
necessarily represent the official position of the CDC.
2Author disclosures: F. K. E. Grant, P. S. Suchdev, R. Flores-Ayala, C. R. Cole, U.
Ramakrishnan, L. J. Ruth, and R. Martorell, no conflicts of interest.
3This trial was registered at clinicaltrials.gov as NCT101088958.
9Abbreviations used: CF, correction factor; Hb, hemoglobin; ID, iron deficiency;
TfR, soluble transferrin receptor; ZP, zinc protoporphyrin.
* To whom correspondence should be addressed. E-mail: ebogrant5@yahoo.
ã 2012 American Society for Nutrition.
Manuscript received June 15, 2011. Initial review completed July 21, 2011. Revision accepted October 10, 2011.
First published online December 7, 2011; doi:10.3945/jn.111.146316.
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Inflammation and iron status of preschoolers111
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