Iron Status of Kenyan Pregnant Women after Adjusting for Inflammation Using BRINDA Regression Analysis and Other Correction Methods.

Serum ferritin concentration is the preferred biomarker to assess population iron status in the absence of inflammation. Interpretation of this biomarker is complicated in populations with a high burden of infection, however, because inflammation increases serum ferritin concentration independently of iron status. We aimed to compare estimates of iron status of Kenyan pregnant women, with circulating ferritin concentrations adjusted for inflammation using newly proposed methods by the BRINDA project, or using previously proposed adjustment methods. We re-analyzed data from pregnant Kenyan women living in a rural area where malaria is highly endemic (n = 470) or in an urban area (n = 402). As proposed by the BRINDA group, we adjusted individual ferritin concentration by internal regression for circulating concentrations of C-reactive protein (CRP) and α1-acid glycoprotein (AGP). Other adjustment methods comprised: (a) arithmetic correction factors based on CRP or AGP; (b) exclusion of subjects with inflammation (CRP >5 mg/L or AGP >1 g/L); and (c) higher ferritin cut-off value (<30 µg/L). We additionally adjusted for Plasmodium infection as appropriate. Lastly, we assessed iron status without adjustment for inflammation. All correction methods increased prevalence of iron deficiency compared to the unadjusted estimates. This increase was more pronounced with the internal regression correction method. The iron deficiency prevalence estimate increased from 53% to 87% in rural Kisumu study and from 30% to 41% in the urban Nairobi study after adjusting for inflammation (CRP and AGP) using the BRINDA internal regression method. When we corrected for both inflammation and Plasmodium infection using the regression correction, it resulted in lower prevalence estimates compared to uninfected women. Application of linear regression methods to adjust circulating ferritin concentration for inflammation leads to markedly decreased point estimates for ferritin concentration and increased estimates for the prevalence of iron deficiency in pregnancy.

The influence and benefits of controlling for inflammation on plasma ferritin and hemoglobin responses following a multi-micronutrient supplement in apparently healthy, HIV+ Kenyan adults.

Hemoglobin and ferritin are important biomarkers of iron status but are both altered by inflammation. We used the inflammation biomarkers C-reactive protein (CRP) and alpha1-acid glycoprotein (AGP) to adjust hemoglobin and ferritin concentrations to clarify interpretation of iron status. Apparently healthy adults who tested positive twice for HIV but who had not reached stage IV or clinical AIDS were randomly allocated to receive a food supplement (n = 17 and 21) or the food plus a micronutrient capsule (MN; 10 men and 34 women, respectively) containing 30 mg iron/d. Hemoglobin, ferritin, CRP, and AGP concentrations were measured at baseline and 3 mo and subjects were divided into 4 groups (reference, no inflammation; incubating, raised CRP; early convalescence, raised AGP and CRP; and late convalescence, raised AGP). Correction factors (the ratios of the median for the reference group over each inflammatory group) improved the consistency of the ferritin but not the hemoglobin results. After correction, ferritin (but not hemoglobin) increased in both men (48 microg/L; P = 0.02) and women (12 microg/L; P = 0.04) who received MN but not in the food-only group. However, hemoglobin did improve in subjects who showed no inflammation both at baseline and mo 3 (P = 0.019), but ferritin did not increase in this group. In conclusion, ferritin concentrations were more closely linked to current inflammation than hemoglobin; hence, correction by inflammation biomarkers improved data consistency. However, low hemoglobin concentrations were the consequence of long-term chronic inflammation and improvements in response to MN supplements were only detected in subjects with no inflammation.

Using plasma acute-phase protein concentrations to interpret nutritional biomarkers in apparently healthy HIV-1-seropositive Kenyan adults.

Inflammation influences the assessment of nutritional status. For example, inflammation reduces plasma retinol concentrations and vitamin A deficiency is overestimated. Conversely inflammation increases plasma ferritin concentrations and Fe deficiency is underestimated. Blood samples were obtained from 163 free-living HIV-1-infected adults, not on continuous medication, anti-retroviral drugs or micronutrients, not unwell and who had not reached WHO stage IV of HIV/AIDS. We used four markers of inflammation, C-reactive protein (CRP), alpha1-acid glycoprotein (AGP), alpha1-antichymotrypsin and erythrocyte sedimentation rate but mainly CRP and AGP were used to separate the subjects into four groups: 'healthy' where both CRP and AGP were normal; 'incubation phase' where CRP was elevated; 'early convalescence' where AGP and CRP were elevated and 'late convalescence' where only AGP was elevated. Correction factors were calculated to remove the influence of inflammation from each biomarker and group where inflammation was present and the data are shown before and after recalculation. The correction increased median plasma retinol concentrations of the whole group from 1.16 to 1.33 micromol/l, comparable with values (mean 1.29 micromol/l) in HIV-negative Kenyan women. Median ferritin concentrations fell by about 50% in both sexes and the number of women with plasma ferritin concentrations < or = 12 microg/l increased from eleven to twenty. The correction also increased plasma carotenoids and Hb but not alpha-tocopherol concentrations. We suggest that the method described to remove the influence of inflammation from nutritional biomarkers should be generally applicable in apparently healthy people and prevents discarding valuable data because of mild inflammation. The method does now need to be tested in other populations.