Correcting for inflammation changes estimates of iron deficiency among rural Kenyan preschool children.
ABSTRACT 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 α-1-acid glycoprotein (AGP)] were determined. Malaria parasitemia was assessed. Subclinical inflammation was defined as CRP >5 mg/L and/or AGP >1 g/L). Four groups were defined based on APP levels: reference (normal CRP 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 = -0.27; P < 0.001), and ZP (r = 0.16; P < 0.001); AGP was correlated with ferritin (r = 0.39; P < 0.001), Hb (r = -0.29; 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 μg/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.
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ABSTRACT: The World Health Organization defines anemia as the point at which the amount of hemoglobin in the circulation falls below World Health Organization cutoffs for specific age and sex groups. Anemia is a worldwide problem of complex etiology and is associated with many factors. The purpose of this review was to describe the biomarkers used to identify the nature of anemia in patients and in the community. The important biomarkers are the automated red cell counts, tests for nutritional deficiencies, hemoglobinopathies, and inflammation. Diseases are important potential initiators of anemia, but biomarkers of specific diseases are not included in this review, only the underlying feature common to all disease - namely, inflammation.Hematology Research and Reviews 01/2013; 4:11-22.
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ABSTRACT: Although anemia in preschool children is most often attributed to iron deficiency, other nutritional, infectious, and genetic contributors are rarely concurrently measured. In a population-based, cross-sectional survey of 858 children 6-35 months of age in western Kenya, we measured hemoglobin, malaria, inflammation, sickle cell, α-thalassemia, iron deficiency, vitamin A deficiency, anthropometry, and socio-demographic characteristics. Anemia (Hb < 11 g/dL) and severe anemia (Hb < 7 g/dL) prevalence ratios (PRs) for each exposure were determined using multivariable modeling. Anemia (71.8%) and severe anemia (8.4%) were common. Characteristics most strongly associated with anemia were malaria (PR: 1.7; 95% confidence interval [CI] = 1.5-1.9), iron deficiency (1.3; 1.2-1.4), and homozygous α-thalassemia (1.3; 1.1-1.4). Characteristics associated with severe anemia were malaria (10.2; 3.5-29.3), inflammation (6.7; 2.3-19.4), and stunting (1.6; 1.0-2.4). Overall 16.8% of anemia cases were associated with malaria, 8.3% with iron deficiency, and 6.1% with inflammation. Interventions should address malaria, iron deficiency, and non-malarial infections to decrease the burden of anemia in this population.The American journal of tropical medicine and hygiene 02/2013; · 2.53 Impact Factor
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ABSTRACT: Hepcidin regulation by competing stimuli such as infection and iron deficiency has not been studied in infants and it's yet unknown whether hepcidin regulatory pathways are fully functional in infants. In this cross-sectional study including 339 Kenyan infants aged 6.0±1.1 months (mean±SD), we assessed serum hepcidin-25, biomarkers of iron status and inflammation, and fecal calprotectin. Prevalence of inflammation, anemia, and iron deficiency was 31%, 71%, 26%, respectively. Geometric mean (±SD) serum hepcidin was 6.0 (±3.4) ng/mL, and was significantly lower in males than females. Inflammation (C-reactive protein and interleukin-6) and iron status (serum ferritin, zinc protoporphyrin and soluble transferrin receptor) were significant predictors of serum hepcidin, explaining nearly 60% of its variance. There were small, but significant differences in serum hepcidin comparing iron deficient anemic (IDA) infants without inflammation to iron-deficient anemic infants with inflammation (1.2 (±4.9) vs. 3.4 (±4.9) ng/mL; P<0.001). Fecal calprotectin correlated with blood/mucus in the stool but not with hepcidin. Similarly, the gut-linked cytokines IL-12 and IL-17 did not correlate with hepcidin. We conclude that hepcidin regulatory pathways are already functional in infancy, but serum hepcidin alone may not clearly discriminate between iron-deficient anemic infants with and without infection. We propose gender-specific reference values for serum hepcidin in iron-replete infants without inflammation.PLoS ONE 01/2013; 8(2):e57513. · 3.73 Impact Factor