Abstract
The determination of iron status is challenging when concomitant infection and inflammation are present because of confounding effects of the acute-phase response on the interpretation of most iron indicators. This review summarizes the effects of inflammation on indicators of iron status and assesses the impact of a regression analysis to adjust for inflammation on estimates of iron deficiency (ID) in low– and high–infection-burden settings. We overviewed cross-sectional data from 16 surveys for preschool children (PSC) (n = 29,765) and from 10 surveys for nonpregnant women of reproductive age (WRA) (n = 25,731) from the Biomarkers Reflecting the Inflammation and Nutritional Determinants of Anemia (BRINDA) project. Effects of C-reactive protein (CRP) and α1-acid glycoprotein (AGP) concentrations on estimates of ID according to serum ferritin (SF) (used generically to include plasma ferritin), soluble transferrin receptor (sTfR), and total body iron (TBI) were summarized in relation to infection burden (in the United States compared with other countries) and population group (PSC compared with WRA). Effects of the concentrations of CRP and AGP on SF, sTfR, and TBI were generally linear, especially in PSC. Overall, regression correction changed the estimated prevalence of ID in PSC by a median of +25 percentage points (pps) when SF concentrations were used, by −15 pps when sTfR concentrations were used, and by +14 pps when TBI was used; the estimated prevalence of ID in WRA changed by a median of +8 pps when SF concentrations were used, by −10 pps when sTfR concentrations were used, and by +3 pps when TBI was used. In the United States, inflammation correction was done only for CRP concentrations because AGP concentrations were not measured; regression correction for CRP concentrations increased the estimated prevalence of ID when SF concentrations were used by 3 pps in PSC and by 7 pps in WRA. The correction of iron-status indicators for inflammation with the use of regression correction appears to substantially change estimates of ID prevalence in low– and high–infection-burden countries. More research is needed to determine the validity of inflammation-corrected estimates, their dependence on the etiology of inflammation, and their applicability to individual iron-status assessment in clinical settings.
Highlights
Despite the negative health consequences of iron deficiency (ID), the magnitude and distribution of ID are largely unknown
The Healthy People 2020 objectives, which aim in part to reduce ID in young children and women of childbearing age, have adopted the use of total body iron (TBI), the log ratio of soluble transferrin receptor to serum ferritin (SF) concentrations, to assess population-level iron status [3]
With the use of select findings from 6 previously published reports from the BRINDA project [25,26,27,28,29,30], this review summarizes the magnitude of the effect of AP proteins ( C-reactive protein (CRP) and acid glycoprotein (AGP)) on iron-status indicators (SF and soluble transferrin receptor (sTfR) concentrations and TBI), and assesses the potential impact of the use of regression to adjust for inflammation on estimates of ID in both low– and high–infection-burden settings
Summary
Despite the negative health consequences of iron deficiency (ID), the magnitude and distribution of ID are largely unknown. With the use of select findings from 6 previously published reports from the BRINDA project [25,26,27,28,29,30], this review summarizes the magnitude of the effect of AP proteins ( CRP and AGP) on iron-status indicators (SF and sTfR concentrations and TBI), and assesses the potential impact of the use of regression to adjust for inflammation on estimates of ID in both low– and high–infection-burden settings. The BRINDA project included national or regionally representative nutrition surveys that met the following inclusion criteria: 1) surveys were conducted after 2004; 2) target groups included preschool children (PSC) aged 6–59 mo, nonpregnant women of reproductive age (WRA) aged 15–49 y, or both groups; and 3) surveys measured $1 indicator of iron status (SF or sTfR concentrations) and $1 biomarker of inflammation (AGP or CRP) [24]. In the high–infection-burden countries, the prevalence of an elevated CRP concentration in WRA (median: 17.8%) was lower than that in PSC (median: 37.5%) in data sets that included information on both populations
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