Adjusting iron and vitamin A status in settings of inflammation: a sensitivity analysis of the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) approach

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ABSTRACT

Background

Accurate assessment of iron and vitamin A status is needed to inform public health decisions, but most population-level iron and vitamin A biomarkers are independently influenced by inflammation.

Objectives

We aimed to assess the reproducibility of the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) regression approach to adjust iron [ferritin, soluble transferrin receptor (sTfR)] and vitamin A [retinol-binding protein (RBP), retinol] biomarkers for inflammation (α-1-acid glycoprotein and C-reactive protein).

Methods

We conducted a sensitivity analysis comparing unadjusted and adjusted estimates of iron and vitamin A deficiency using the internal-survey regression approach from BRINDA phase 1 (16 surveys in children, 10 surveys in women) and 13 additional surveys for children and women (BRINDA phase 2).

Results

The relations between inflammation and iron or vitamin A biomarkers were statistically significant except for vitamin A biomarkers in women. Heterogeneity of the regression coefficients across surveys was high. Among children, internal-survey adjustments increased the estimated prevalence of depleted iron stores (ferritin <12 µg/L) by a median of 11 percentage points (pp) (24 pp and 9 pp in BRINDA phase 1 and phase 2, respectively), whereas estimates of iron-deficient erythropoiesis (sTfR >8.3 mg/L) decreased by a median of 15 pp (15 pp and 20 pp in BRINDA phase 1 and phase 2, respectively). Vitamin A deficiency (RBP <0.7 µmol/L or retinol <0.7 µmol/L) decreased by a median of 14 pp (18 pp and 8 pp in BRINDA phase 1 and phase 2, respectively) in children. Adjustment for inflammation in women resulted in smaller differences in estimated iron deficiency than in children.

Conclusions

Our findings are consistent with previous BRINDA conclusions that not accounting for inflammation may result in an underestimation of iron deficiency and overestimation of vitamin A deficiency. Research is needed to understand the etiology of the heterogeneity in the regression coefficients before a meta-analyzed regression correction can be considered.

Keywords:

biomarkers
inflammation
iron
meta-analysis
micronutrient
nutritional assessment
vitamin A

Abbreviations used:

AGP
α-1-acid glycoprotein
BRINDA
Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia
CRP
C-reactive protein
pp
percentage point
RBP
retinol-binding protein
sTfR
soluble transferrin receptor.

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Supported by the Bill & Melinda Gates Foundation, CDC, Eunice Kennedy Shriver National Institute of Child Health and Human Development, HarvestPlus, and the United States Agency for International Development.

The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the CDC.

Supplemental Tables 1–9 are available from the “Supplementary data ” link in the online posting of the article and from the same link in the online table of contents at https://academic.oup.com/ajcn/.

Data described in the article, code book, and analytic code will be made available upon request pending approval from the BRINDA steering committee and country representatives.