Estimating the Hidden Burden of Iron Deficiency Among African Children

Abstract

Background: Iron 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 commonly underestimated in Africa because most measures of iron status are altered by inflammation and infections such as malaria. Methods: We assayed iron and inflammatory biomarkers in 4,853 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, malaria parasitaemia, inflammation, stunting, underweight, and wasting. We defined ID using the WHO ferritin-based definition (ferritin 5mg/L)) and then used regression modelling, correcting for inflammation and malaria, to estimate 'true' prevalence of ID. We further investigated the utility of other iron biomarkers in predicting ID. Findings: The prevalence of ID was highest at one year of age and in male children. Stunting and underweight were associated with anaemia and iron deficient erythropoiesis. Inflammation and malaria parasitaemia significantly influenced all iron biomarkers, although transferrin saturation was least affected. The WHO definition of ID did not identify 27·0% of Burkinabe, 21·4% of Kenyan, 20·0% of Ugandan, 16·8% of Gambian, and 8·5% of South African children with 'true' iron deficiency. This 'hidden burden' increased with age and with increasing prevalence of inflammation and malaria. We observed similar prevalences of ID using regression modelling and transferrin saturation <11%. Interpretation: The prevalence of ID may be underestimated in African children using the WHO definition because inflammation and malaria obscure the 'true' burden. Transferrin saturation is least affected by inflammation and malaria and may more accurately determine the burden of ID. Funding Statement: This work was funded by Wellcome (Grant numbers [110255/Z/15/Z to SHA], [202800/Z/16/Z to TNW; 106289/Z/14/Z to AJM; and 064693, 079110, 095778 to AME] and with core awards to the KEMRI-Wellcome Trust Research Programme (203077/Z/16/Z), The Wellcome Centre for Human Genetics (090532/Z/09/Z, 203141) and the Wellcome Sanger Institute (098051, 206194). AJM was also supported by an Oxford University Clinical Academic School Transitional Fellowship and the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. JMM was funded through the DELTAS Africa Initiative (DEL-15-003). The DELTAS Africa Initiative is an independent funding scheme of the African Academy of Sciences (AAS)'s Alliance for Accelerating Excellence in Science in Africa (AESA) and supported by the New Partnership for Africa's Development Planning and Coordinating Agency (NEPAD Agency) with funding from the Wellcome Trust [107769/Z/10/Z] and the UK government. The Gambian studies were supported by National Institute of Child Health and Development, Bill and Melinda Gates Foundation, core funding MC-A760-5QX00 to the MRC Unit The Gambia/MRC International Nutrition Group by the UK MRC and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement. This project also received funding from the European Research Council (ERC) under the European Union’s (Seventh Framework Programme [FP7/2007-2013]) (Grant agreement No 294557 to AVSH). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: Ethical approvals were obtained for Kilifi, Kenya (by the Scientific Ethics Review Unit of the Kenya Medical Research Institute (KEMRI/SERU/CGMR-C/046/3257/2983)); Entebbe, Uganda (locally by the Uganda Virus Research Institute (GC/127/12/07/32) and Uganda National Council for Science and Technology (MV625), and in the UK by the London School of Hygiene and Tropical Medicine (A340) and Oxford Tropical Research (OTR) (39-12, 42-14 and 37-15) Ethics Committees); Banfora, Burkina Faso (by Ministere de la Recherche Scientifique et de l’Innovation in Burkina Faso (2014-12-151) and the OTR Ethics Committees (41-12)); Soweto, South Africa (by the University of Witwatersrand Human Research (M130714) and the OTR Ethics Committees (1042-13 and 42-14)); and West Kiang, The Gambia (by the Gambian Government/Medical Research Council Ethics Committee (874/830)).