Abstract
Background: Iron deficiency is thought to be one of the most prevalent micronutrient deficiencies globally, but an accurate assessment in populations who are frequently exposed to infections is impeded by the inflammatory response, which causes iron-biomarker alterations.Objectives: We assessed the relation between soluble transferrin receptor (sTfR) concentrations and inflammation and malaria in preschool children (PSC) (age range: 6–59 mo) and women of reproductive age (WRA) (age range: 15–49 y) and investigated adjustment algorithms to account for these effects.Design: Cross-sectional data from the Biomarkers Reflecting the Inflammation and Nutritional Determinants of Anemia (BRINDA) project from 11,913 PSC in 11 surveys and from 11,173 WRA in 7 surveys were analyzed individually and combined with the use of a meta-analysis. The following 3 adjustment approaches were compared with estimated iron-deficient erythropoiesis (sTfR concentration >8.3 mg/L): 1) the exclusion of individuals with C-reactive protein (CRP) concentrations >5 mg/L or α-1-acid glycoprotein (AGP) concentrations >1 g/L, 2) the application of arithmetic correction factors, and 3) the use of regression approaches.Results: The prevalence of elevated sTfR concentrations incrementally decreased as CRP and AGP deciles decreased for PSC and WRA, but the effect was more pronounced for AGP than for CRP. Depending on the approach used to adjust for inflammation, the estimated prevalence of iron-deficient erythropoiesis decreased by 4.4–14.6 and 0.3–9.5 percentage points in PSC and WRA, respectively, compared with unadjusted values. The correction-factor approach yielded a more modest reduction in the estimated prevalence of iron-deficient erythropoiesis than did the regression approach. Mostly, adjustment for malaria in addition to AGP did not significantly change the estimated prevalence of iron-deficient erythropoiesis.Conclusions: sTfR may be useful to assess iron-deficient erythropoiesis, but inflammation influences its interpretation, and adjustment of sTfR for inflammation and malaria should be considered. More research is warranted to evaluate the proposed approaches in different settings, but this study contributes to the evidence on how and when to adjust sTfR for inflammation and malaria.
Highlights
The accurate estimation of the prevalence and severity of iron deficiency in a population is important for programming and intervention strategies to reduce iron deficiency and anemia
An expert consultation held by the WHO and CDC in 2004 concluded that ferritin concentrations are reflective of liver iron stores, which are responsive to iron interventions, and should, Report of the collaborative research group called Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA), which was formed in 2012 by the Centers for Disease Control and Prevention (CDC), the Global Alliance for Improved Nutrition (GAIN), and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Our study sample was restricted to participants with no missing values for soluble transferrin receptor (sTfR), C-reactive protein (CRP), acid glycoprotein (AGP), or malaria; this resulted in a total loss of 60.0% (11,913 of 29,766) of the observations that met the BRINDA inclusion criteria in preschool children (PSC) and 56.6% (11, 173 of 25,731) in women of reproductive age (WRA)
Summary
The accurate estimation of the prevalence and severity of iron deficiency in a population is important for programming and intervention strategies to reduce iron deficiency and anemia. An expert consultation held by the WHO and CDC in 2004 concluded that ferritin concentrations are reflective of liver iron stores, which are responsive to iron interventions, and should, Report of the collaborative research group called Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA), which was formed in 2012 by the Centers for Disease Control and Prevention (CDC), the Global Alliance for Improved Nutrition (GAIN), and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). Supported by the Bill & Melinda Gates Foundation, the CDC, the Global Alliance for Improved Nutrition, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development The following 3 adjustment approaches were compared with estimated iron-deficient erythropoiesis (sTfR concentration .8.3 mg/L): 1) the exclusion of individuals with C-reactive protein (CRP) concentrations .5 mg/L or a-1-acid glycoprotein (AGP) concentrations .1 g/L, 2) the application of arithmetic correction factors, and 3) the use of regression approaches
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