Estimating the burden of iron deficiency among African children

John Muthii Muriuki ,Thomas N Williams ,Alireza Morovat ,Alison M Elliott ,Parminder S Suchdev ,Amidou Diarra ,Wandia Kimita ,Emily L Webb ,Adrian V S Hill ,Rosie J Crane ,Clare Cutland ,Swaib A Lule ,Sodiomon B Sirima ,Alfred B Tiono ,Francis M Ndungu ,Shabir A Madhi ,Andrew M Prentice ,Alexander J Mentzer ,James A Berkley ,Alex Macharia ,Philip Bejon ,Sarah H Atkinson

doi:10.1186/s12916-020-1502-7

Abstract

BackgroundIron deficiency (ID) is a major public health burden in African children and accurate prevalence estimates are important for effective nutritional interventions. However, ID may be incorrectly estimated in Africa because most measures of iron status are altered by inflammation and infections such as malaria. Through the current study, we have assessed different approaches to the prediction of iron status and estimated the burden of ID in African children.MethodsWe assayed iron and inflammatory biomarkers in 4853 children aged 0–8 years from Kenya, Uganda, Burkina Faso, South Africa, and The Gambia. We described iron status and its relationship with age, sex, inflammation, and malaria parasitemia. We defined ID using the WHO guideline (ferritin < 12 μg/L or < 30 μg/L in the presence of inflammation in children < 5 years old or < 15 μg/L in children ≥ 5 years old). We compared this with a recently proposed gold standard, which uses regression-correction for ferritin levels based on the relationship between ferritin levels, inflammatory markers, and malaria. We further investigated the utility of other iron biomarkers in predicting ID using the inflammation and malaria regression-corrected estimate as a gold standard.ResultsThe prevalence of ID was highest at 1 year of age and in male infants. Inflammation and malaria parasitemia were associated with all iron biomarkers, although transferrin saturation was least affected. Overall prevalence of WHO-defined ID was 34% compared to 52% using the inflammation and malaria regression-corrected estimate. This unidentified burden of ID increased with age and was highest in countries with high prevalence of inflammation and malaria, where up to a quarter of iron-deficient children were misclassified as iron replete. Transferrin saturation < 11% most closely predicted the prevalence of ID according to the regression-correction gold standard.ConclusionsThe prevalence of ID is underestimated in African children when defined using the WHO guidelines, especially in malaria-endemic populations, and the use of transferrin saturation may provide a more accurate approach. Further research is needed to identify the most accurate measures for determining the prevalence of ID in sub-Saharan Africa.

Highlights

Iron deficiency (ID) is a major public health burden in African children and accurate prevalence estimates are important for effective nutritional interventions
We found that World Health Organization (WHO)-defined ID underestimated the burden of ID in African children compared to regression correction, which predicts ferritin levels in the absence of inflammation and malaria
We used a ferritinbased definition of ID since other iron biomarkers have less standardized assays and less well-established cut-offs for ID. Another limitation of our study was that Transferrin saturation (TSAT), the best performing marker in predicting regression-corrected ID, was not available for Ugandan and South African children, and it outperformed all other iron markers, it had an Area under curve (AUC) of only 0.77. In this large-scale study including more than 4800 children in five countries across Africa, we explored a wide range of iron biomarkers to more accurately estimate prevalence of ID in countries with a high burden of childhood infections including malaria

Summary

Introduction

Iron deficiency (ID) is a major public health burden in African children and accurate prevalence estimates are important for effective nutritional interventions. ID may be incorrectly estimated in Africa because most measures of iron status are altered by inflammation and infections such as malaria. Iron deficiency (ID) is the commonest nutrient deficiency affecting over 2 billion people worldwide and is a major public health burden in African children [1, 2]. Despite its detrimental effects on health, the true burden of ID in African children remains largely unknown because of the complex interactions of the biochemical markers of ID with inflammation and infections including malaria [4, 5]. We hypothesized that the WHO definition of ID may underestimate the prevalence of ID in areas with high burdens of inflammation and malaria

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