Archive for June, 2017

Adjusting soluble transferrin receptor concentrations for inflammation: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project

Rohner F, Namaste SML, Larson LM, Addo OY, Mei Z, Suchdev PS, Williams AM, Sakr Ashour FA, Rawat R, Raiten DJ, Northrop-Clewes CA

June 2017 – American Journal of Clinical Nutrition

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. We assessed the relation between soluble transferrin receptor (sTfR) concentrations and inflammation and malaria in preschool children (PSC) and women of reproductive age (WRA) and investigated adjustment algorithms to account for these effects using cross-sectional data from the Biomarkers Reflecting the Inflammation and Nutritional Determinants of Anemia (BRINDA) project. 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. 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.

Adjusting total body iron for inflammation: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project.

Mei Z, Namaste SML, Serdula M, Suchdev PS, Rohner F, Flores-Ayala R, Addo OY, Raiten DJ

June 2017 – American Journal of Clinical Nutrition

Total body iron (TBI) that is calculated from ferritin and soluble transferrin receptor (sTfR) allows for the evaluation of the full range of iron status from deficiency to excess. However, both ferritin and sTfR are affected by inflammation and malaria, which may require a statistical adjustment. TBI has been used to assess iron status in the United States, but its use worldwide and in settings with inflammation has been limited. We examine whether inflammation-adjusted ferritin and sTfR concentrations affect TBI values and the prevalence of low TBI (<0 mg/kg) in preschool children (PSC) and women of reproductive age (WRA) using cross-sectional data from the Biomarkers Reflecting the Inflammation and Nutritional Determinants of Anemia (BRINDA) project. TBI and the prevalence of low TBI were compared following 3 adjustment approaches for ferritin and sTfR: 1) the exclusion of individuals with inflammation (C-reactive protein concentration >5 mg/L or α-1-acid glycoprotein concentration >1 g/L), 2) the application of arithmetic correction factors, and 3) the use of regression correction. Regardless of the method that was used to adjust ferritin and sTfR for inflammation, the adjusted mean TBI decreased in both PSC and WRA compared with unadjusted values. Subsequently, inflammation-adjusted TBI increased the prevalence of low TBI by a median of 4-14 percentage points (pps) in PSC and 1-3 pps in WRA compared with unadjusted TBI. The regression approach resulted in a greater median increase than was achieved with the exclusion or correction-factor approaches, and accounting for malaria in addition to inflammation did not have an added effect on the prevalence estimates.

Adjusting ferritin concentrations for inflammation: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project

Namaste SML, Rohner F, Huang J, Bhushan NL, Flores-Ayala R, Kupka R, Mei Z, Rawat R, Williams AM, Raiten DJ, Northrop-Clewes CA, Suchdev PS

June 2017 – American Journal of Clinical Nutrition

The accurate estimation of iron deficiency is important in planning and implementing interventions. Ferritin is recommended as the primary measure of iron status, but interpretability is challenging in settings with infection and inflammation. We assessed the relation between ferritin 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 using cross-sectional data from 15 surveys for PSC (n = 27,865) and 8 surveys for WRA (24,844), from the Biomarkers Reflecting the Inflammation and Nutritional Determinants of Anemia (BRINDA) project. Several approaches were explored to estimate depleted iron stores, including a regression correction approach. Depending on the approach used to adjust for inflammation (CRP plus AGP), the estimated prevalence of depleted iron stores increased by 7–25 and 2–8 absolute median percentage points for PSC and WRA, respectively, compared with unadjusted values. Adjustment for malaria in addition to CRP and AGP did not substantially change the estimated prevalence of depleted iron stores. This approach appears to mathematically reflect the linear relation of ferritin concentrations with acute-phase proteins. More research is warranted to validate the proposed approaches, but this study contributes to the evidence base to guide decisions about how and when to adjust ferritin for inflammation.

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