- freely available
Nutrients 2017, 9(6), 576; https://doi.org/10.3390/nu9060576
- the prevalence and assessment of ID;
- the benefit/harm ratio of iron; and
- the national strategies to fight ID and their impact.
2. Iron Deficiency in Africa: Prevalence, Causes and Diagnosis Tools
- This peptide acts as the master regulator of iron (9: it controls its dietary absorption, storage, and tissue distribution.
- Hepcidin integrates signals from iron in serum, liver and bone marrow and from inflammation; it could thus act as a biomarker reflecting iron status, but its effective use as such still needs more research.
- Hepcidin prevents iron absorption in inflammatory contexts and may blunt the efficacy of iron interventions in such contexts.
- Precise, reliable and comparable data on the prevalence of ID are lacking in many countries and population groups. Among other factors, this is due to biomarkers being frequently biased by inflammation.
- ID is a worrying reality in young children and women, which does not seem to be currently decreasing.
- ID-associated factors vary according to regions and countries, but inappropriate eating habits, and high burdens of infections and parasitic diseases are critical.
- Initiate large epidemiological surveys on representative populations and with appropriate ID biomarkers including inflammatory markers.
- Focus on post-partum anemia and ID, which are under-studied.
- Improve ID biomarkers and their cut-offs and set clear interpretations according to context of use.
3. Benefits and Risks of Iron Interventions
- Clear benefits regarding pregnancy, growth and development:
- Decreased maternal anemia
- Increased infant’s birth weight
- Improved cognitive capacity of children under 2 years
- Potential risks may in high infectious context:
- Enhanced pathogen growth (increased availability of iron in blood and unabsorbed iron in the gut).
- Increased infectious risk in the absence of monitoring and treatment programs.
- However, benefits outweigh risks, in particular when infection can be monitored and controlled.
- Caution should remain, especially when infants and children are concerned and, if possible, interventions should be targeted to iron-deficient subjects.
- Better assessments of the impact of iron intervention on growth outcomes and cognition in younger children.
- Exploration of the harms of high/excessive iron status and associated outcomes, especially in pregnancy.
- Investigations on the impact of iron on gut microbiota in various populations (e.g., pregnant women).
4. Strategies for Iron Intervention
- Increasing the dietary supply of iron-rich foods, among which animal-sourced ones offer highly bioavailable iron. This ideal solution is often difficult to implement for economic and practical reasons.
- Delaying cord clamping at birth is a simple but efficient means to increase the infant’s body iron stores, which could be developed through appropriate education of health care professionals.
- Fortifying some foods within the usual diet can be done centrally on the whole supply of staple foods such as flour, without targeting population groups or individuals. Home fortification with MNPs or industrially fortified processed foods (e.g., biscuits, cereals, infant formulae) may allow some personalization and thus a better adaptation to individual’s needs.
- Supplementing vulnerable groups is recommended by WHO for populations, living in settings where anemia prevalence is over 40%, including menstruating women , post-partum women  and children above six months . According to WHO guidelines, supplementation is today most often recommended on a daily basis.
- The difficulty of identifying and then reaching the target population groups and individuals.
- The lack of awareness, knowledge and understanding (especially regarding for home fortification) of caregivers, but also health professionals.
- The poor adherence to programs or prescriptions.
- The poor availability of iron-containing supplies (supplement, fortified staple foods, and fortified products), which may be missing at point of supply or purchase.
- The cost: Even for government-funded supplementation programs, which is not always the case, the subject should often pay a part of the cost. Iron-fortified products are often too expensive for the populations who would need them.
- The low bioavailability of some iron forms. Several countries, such as Morocco, are currently considering a change to the more bioavailable NaFeEDTA in their mandatory fortification programs.
- The infectious context: Infants and young children may be especially vulnerable to infection, both because they are exposed to pathogens and because their immune system is still immature. In addition, infection-induced hepcidin secretion limits iron absorption in contexts where the hygiene level is low .
- Many African countries have governmental programs to fortify flour and to supplement pregnant women; supplementation of children is not systematic.
- Coverage and efficacy of these actions are variable, but usually far from optimal, for many reasons (difficulty to reach the target population, cost and iron bioavailability of supplement/fortified foods, lack of awareness and compliance, etc.).
- The risk of increased infections, especially in young children, acts as a bottleneck in areas with high infectious disease burden.
- Improving availability of iron (chelated forms, absorption enhancers, etc.) would help to lower iron dose, thus to decrease harms, while keeping a similar efficacy.
- Using prebiotics together with iron could lower risk of enteropathogen growth and infections in infants.
- Demonstrate that increased clean water availability, washing practices and overall hygiene increase the safety and efficacy of iron intervention in young children.
- Confirm and extend studies about prebiotics and determine which one(s) would be best adapted to an African context and to various ages and populations.
5. Fortified Food Products: Which Products for Which Target Group?
Conflicts of Interest
|IUNS||International Union of Nutrition Societies|
|MCHC||Mean Cell Hemoglobin Concentration|
|sTfR||Soluble Transferrin Receptor|
|TIBC||Total Iron Binding Capacity|
- Pasricha, S.R.; Drakesmith, H. Iron deficiency anemia: Problems in diagnosis and prevention at the population level. Hematol. Oncol. Clin. N. Am. 2016, 30, 309–325. [Google Scholar] [CrossRef] [PubMed]
- Stevens, G.A.; Finucane, M.M.; De-Regil, L.M.; Paciorek, C.J.; Flaxman, S.R.; Branca, F.; Pena-Rosas, J.P.; Bhutta, Z.A.; Ezzati, M. Global, regional, and national trends in haemoglobin concentration and prevalence of total and severe anaemia in children and pregnant and non-pregnant women for 1995–2011: A systematic analysis of population-representative data. Lancet. Glob. Health 2013, 1, e16–e25. [Google Scholar] [CrossRef]
- Diouf, S.; Folquet, M.; MBofung, K.; Ndiaye, O.; Brou, K.; Dupont, C.; N’Dri, D.; Vuillerod, M.; Azais-Braesco, V.; Tetanye, E. Pprevalence and determinants of anemia in young children in french-speaking africa. Role of iron deficiency. Arch. Pediatr. 2015, 22, 1188–1197. [Google Scholar] [CrossRef] [PubMed]
- World Health Organization. Vitamin and Mineral Nutrition Information System (VMNIS). Anaemia Database by Country. Available online: http://www.who.int/vmnis/database/anaemia/countries/en/#E (accessed on 27 February 2017).
- Shisana, O.; Labadarios, D.; Rehle, T.; Simbayi, L.; Zuma, K.; Dhansay, A.; Reddy, P.; Parker, W.; Hoosain, E.; Naidoo, P.; et al. The South African National Health and Nutrition Examination Survey, 2012: SANHANES-1: The Health and Nutritional Status of the Nation. Available online: http://www.hsrc.ac.za/en/research-data/view/6493 (accessed on 2 June 2017).
- Abla, K.; Bekakria, A.; Bouziane, K. Prévalence et facteurs de risque de l’anémie chez un groupe d’enfants âgés de 1 à 24 mois à tébessa (une ville de l’est algérien). Cah. Nut. Diet. 2016, 51, 157–160. [Google Scholar] [CrossRef]
- Ministry of Health (MoH). Ministry of Health and Population. Egypt-demographic and Health Survey-Main Findings. Available online: http://dhsprogram.com/what-we-do/survey/survey-display-397.cfm (accessed on 31 May 2017).
- Al Ghwass, M.M.; Halawa, E.F.; Sabry, S.M.; Ahmed, D. Iron deficiency anemia in an Egyptian pediatric population: A cross-sectional study. Ann. Afr. Med. 2015, 14, 25–31. [Google Scholar] [PubMed]
- MSLS. Enquête Démographique et de Santé et à Indicateurs Multiples. Available online: http://dhsprogram.Com/what-we-do/survey/survey-display-311.Cfm (accessed on 27 February 2017).
- PIPAF & Consortium. Evaluation des Carences en Vitamine A, fer et Folate en Côté D’ivoire6 Projet Ivoirien de Promotion des Aliments Fortifiés; Institute National de Santé Publique: Abidjan, Côte d’Ivoire, 2008. [Google Scholar]
- GBOS. The Gambia Demographic and Health Survey 2013. Available online: http://dhsprogram.Com/what-we-do/survey/survey-display-425.Cfm (accessed on 27 February 2017).
- GSS. Ghana Sstatistical Services-Demographic and Health Survey 2014. Available online: http://dhsprogram.Com/what-we-do/survey/survey-display-437.Cfm (accessed on 27 February 2017).
- Kisiangani, I.; Mbakaya, C.; Makokha, A.; Magu, D. Assessment of iron status among preschool children (6 to 59 months) with and without malaria in western province, Kenya. Pan Afr. Med. J. 2015, 21, 62. [Google Scholar] [CrossRef] [PubMed]
- El Hamdouchi, A.; El Khari, K.; Rjimati, L.; El Haloui, N.; El Mzibri, M.; Aguenaou, H.; Mokhtar, N. Impact de l’enrichissement de la farine en fer élémentaire sur la prévalence de l’anémie chez les enfants en âge préscolaire au maroc. East. Mediterr. Health J. 2010, 16, 1148–1152. [Google Scholar] [PubMed]
- Rezk, M.; Marawan, H.; Dawood, R.; Masood, A.; Abo-Elnasr, M. Prevalence and risk factors of iron-deficiency anaemia among pregnant women in rural districts of menoufia governorate, Egypt. J. Obstet. Gynaecol. 2015, 35, 663–666. [Google Scholar] [CrossRef] [PubMed]
- Engmann, C.; Adanu, R.; Lu, T.S.; Bose, C.; Lozoff, B. Anemia and iron deficiency in pregnant Ghanaian women from urban areas. Int. J. Gynaecol. Obstet. 2008, 101, 62–66. [Google Scholar] [CrossRef] [PubMed]
- FAO. Profil Nutitionnel de Pays. Royaume du Maroc. Available online: http://www.Fao.Org/ag/agn/nutrition/profiles_by_country_fr.Stm#africa (accessed on 27 February 2017).
- World Health Organization. Haemoglobin Concentrations for the Diagnosis of Anaemia and Assessment of Severity. Vitamin and Mineral Nutrition Information System. Geneva. 2011. Available online: http://www.Who.Int/vmnis/indicators/haemoglobin (accessed on 19 May 2017).
- Zimmermann, M.B.; Chaouki, N.; Hurrell, R.F. Iron deficiency due to consumption of a habitual diet low in bioavailable iron: A longitudinal cohort study in moroccan children. AJCN 2005, 81, 115–121. [Google Scholar]
- Benjelloun, S. Nutrition transition in Morocco. PHN 2002, 5, 135–140. [Google Scholar] [CrossRef] [PubMed]
- Zaida, F.; Bureau, F.; Guyot, S.; Sedki, A.; Lekouch, N.; Arhan, P.; Bougle, D. Iron availability and consumption of tea, vervain and mint during weaning in Morocco. Ann. Nut. Metab. 2006, 50, 237–241. [Google Scholar] [CrossRef] [PubMed]
- Admou, B.; Essaadouni, L.; Krati, K.; Zaher, K.; Sbihi, M.; Chabaa, L.; Belaabidia, B.; Alaoui-Yazidi, A. Atypical celiac disease: From recognizing to managing. Gastroenterol. Res. Pract. 2012, 2012, 637187. [Google Scholar] [CrossRef] [PubMed]
- Osazuwa, F.; Ayo, O.M.; Imade, P. A significant association between intestinal helminth infection and anaemia burden in children in rural communities of edo state, Nigeria. N. Am. J. Med. Sci. 2011, 3, 30–34. [Google Scholar] [CrossRef] [PubMed]
- Shaw, J.G.; Friedman, J.F. Iron deficiency anemia: Focus on infectious diseases in lesser developed countries. Anemia 2011, 2011, 260380. [Google Scholar] [CrossRef] [PubMed]
- WHO. Global Health Observatory Data. Soil-Transmitted Helminthiases. Available online: http://www.who.int/gho/neglected_diseases/soil_transmitted_helminthiases/en/ (accessed on 27 February 2017).
- Hussein, W.M.; Anwar, W.A.; Attaleb, M.; Mazini, L.; Forsti, A.; Trimbitas, R.D.; Khyatti, M. A review of the infection-associated cancers in north African countries. Infect. Agent. Cancer 2016, 11, 35. [Google Scholar] [CrossRef] [PubMed]
- Hudak, L.; Jaraisy, A.; Haj, S.; Muhsen, K. An updated systematic review and meta-analysis on the association between helicobacter pylori infection and iron deficiency anemia. Helicobacter 2017, 22, e12330. [Google Scholar] [CrossRef] [PubMed]
- Ciacci, C.; Sabbatini, F.; Cavallaro, R.; Castiglione, F.; Di Bella, S.; Iovino, P.; Palumbo, A.; Tortora, R.; Amoruso, D.; Mazzacca, G. Helicobacter pylori impairs iron absorption in infected individuals. Dig. Liver Dis. 2004, 36, 455–460. [Google Scholar] [CrossRef] [PubMed]
- Sarker, S.A.; Davidsson, L.; Mahmud, H.; Walczyk, T.; Hurrell, R.F.; Gyr, N.; Fuchs, G.J. Helicobacter pylori infection, iron absorption, and gastric acid secretion in bangladeshi children. AJCN 2004, 80, 149–153. [Google Scholar]
- Thankachan, P.; Muthayya, S.; Sierksma, A.; Eilander, A.; Thomas, T.; Duchateau, G.S.; Frenken, L.G.; Kurpad, A.V. Helicobacter pylori infection does not influence the efficacy of iron and vitamin B(12) fortification in marginally nourished Indian children. Eur. J. Clin. Nut. 2010, 64, 1101–1107. [Google Scholar] [CrossRef] [PubMed]
- Lopez de Romana, D.; Pizarro, F.; Diazgranados, D.; Barba, A.; Olivares, M.; Brunser, O. Effect of helicobacter pylori infection on iron absorption in asymptomatic adults consuming wheat flour fortified with iron and zinc. Biol. Trace Elem. Res. 2011, 144, 1318–1326. [Google Scholar] [CrossRef] [PubMed]
- WHO. Assessing the Iron Status of Populations: Report of a Joint World Health Organization/Centers for Disease Control and Technical Consultation on the Assessment of Iron Status at the Population Level, 2nd ed.; WHO: Geneva, Switzerland, 2004. [Google Scholar]
- Phiri, K.S.; Calis, J.C.; Siyasiya, A.; Bates, I.; Brabin, B.; van Hensbroek, M.B. New cut-off values for ferritin and soluble transferrin receptor for the assessment of iron deficiency in children in a high infection pressure area. J. Clin. Pathol. 2009, 62, 1103–1106. [Google Scholar] [CrossRef] [PubMed]
- Phiri, K.S.; Calis, J.C.; Kachala, D.; Borgstein, E.; Waluza, J.; Bates, I.; Brabin, B.; van Hensbroek, M.B. Improved method for assessing iron stores in the bone marrow. J. Clin. Pathol. 2009, 62, 685–689. [Google Scholar] [CrossRef] [PubMed]
- Ganz, T. Hepcidin and iron regulation, 10 years later. Blood 2011, 117, 4425–4433. [Google Scholar] [CrossRef] [PubMed]
- Suchdev, P.S.; Namaste, S.M.; Aaron, G.J.; Raiten, D.J.; Brown, K.H.; Flores-Ayala, R. Overview of the biomarkers reflecting inflammation and nutritional determinants of anemia (BRINDA) project. Adv. Nutr. 2016, 7, 349–356. [Google Scholar] [CrossRef] [PubMed]
- IUNS. Iron Task Force. International Union of Nutrition Sciences/Micronutrient Forum/Nih Joint Taskforce: Risk and Benefits of Iron. Report 2015 report. Available online: http://www.iuns.org/resources/risk-and-benefits-of-iron-report-2015/ (accessed on 31 May 2017).
- WHO. Daily Iron Supplementation in Adult Women and Adolescent Girls. Available online: http://www.Who.Int/nutrition/publications/micronutrients/guidelines/daily_iron_supp_womenandgirls/en/ (accessed on 31 May 2017).
- WHO. Iron Supplementation in Postpartum Women. Available online: http://www.Who.Int/nutrition/publications/micronutrients/guidelines/daily_iron_supp_postpartum_women/en/ (accessed on 31 May 2017).
- WHO. Daily Iron Supplementation in Infants and Children. Available online: http://www.who.int/nutrition/publications/micronutrients/guidelines/daily_iron_supp_childrens/en/ (accessed on 31 May 2017).
- Lumbiganon, P.; Laopaiboon, M.; Intarut, N.; Vogel, J.P.; Souza, J.P.; Gulmezoglu, A.M.; Mori, R. Indirect causes of severe adverse maternal outcomes: A secondary analysis of the who multicountry survey on maternal and newborn health. BJOG 2014, 121, 32–39. [Google Scholar] [CrossRef] [PubMed]
- Brabin, B.J.; Hakimi, M.; Pelletier, D. An analysis of anemia and pregnancy-related maternal mortality. J. Nutr. 2001, 131, 604S–615S. [Google Scholar] [PubMed]
- Pena-Rosas, J.P.; De-Regil, L.M.; Garcia-Casal, M.N.; Dowswell, T. Daily Oral Iron Supplementation during Pregnancy. Available online: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD004736.pub5/pdf (accessed on 2 June 2017).
- Mwangi, M.N.; Roth, J.M.; Smit, M.R.; Trijsburg, L.; Mwangi, A.M.; Demir, A.Y.; Wielders, J.P.; Mens, P.F.; Verweij, J.J.; Cox, S.E.; et al. Effect of daily antenatal iron supplementation on plasmodium infection in kenyan women: A randomized clinical trial. JAMA 2015, 314, 1009–1020. [Google Scholar] [CrossRef] [PubMed]
- Milman, N. Postpartum anemia I: definition, prevalence, causes, and consequences. Ann. Hematol. 2011, 90, 1247–1253. [Google Scholar] [CrossRef] [PubMed]
- Murray-Kolb, L.E.; Beard, J.L. Iron deficiency and child and maternal health. AJCN 2009, 89, 946S–950S. [Google Scholar] [CrossRef] [PubMed]
- Low, M.; Farrell, A.; Biggs, B.A.; Pasricha, S.R. Effects of daily iron supplementation in primary-school-aged children: Systematic review and meta-analysis of randomized controlled trials. CMAJ 2013, 185, E791–E802. [Google Scholar] [CrossRef] [PubMed]
- Thompson, J.; Biggs, B.A.; Pasricha, S.R. Effects of daily iron supplementation in 2- to 5-year-old children: Systematic review and meta-analysis. Pediatrics 2013, 131, 739–753. [Google Scholar] [CrossRef] [PubMed]
- Iannotti, L.L.; Tielsch, J.M.; Black, M.M.; Black, R.E. Iron supplementation in early childhood: Health benefits and risks. AJCN 2006, 84, 1261–1276. [Google Scholar]
- Brissot, P. Optimizing the diagnosis and the treatment of iron overload diseases. Expert Rev. Gastroenterol. Hepatol. 2016, 10, 359–370. [Google Scholar] [CrossRef] [PubMed]
- Sazawal, S.; Black, R.E.; Ramsan, M.; Chwaya, H.M.; Stoltzfus, R.J.; Dutta, A.; Dhingra, U.; Kabole, I.; Deb, S.; Othman, M.K.; et al. Effects of routine prophylactic supplementation with iron and folic acid on admission to hospital and mortality in preschool children in a high malaria transmission setting: Community-based, randomised, placebo-controlled trial. Lancet 2006, 367, 133–143. [Google Scholar] [CrossRef]
- Zlotkin, S.; Newton, S.; Aimone, A.M.; Azindow, I.; Amenga-Etego, S.; Tchum, K.; Mahama, E.; Thorpe, K.E.; Owusu-Agyei, S. Effect of iron fortification on malaria incidence in infants and young children in Ghana: A randomized trial. JAMA 2013, 310, 938–947. [Google Scholar] [CrossRef] [PubMed]
- Malan, L.; Baumgartner, J.; Calder, P.C.; Zimmermann, M.B.; Smuts, C.M. n-3 long-chain pufas reduce respiratory morbidity caused by iron supplementation in iron-deficient south african schoolchildren: A randomized, double-blind, placebo-controlled intervention. AJCN 2015, 101, 668–679. [Google Scholar] [CrossRef] [PubMed]
- Soofi, S.; Cousens, S.; Iqbal, S.P.; Akhund, T.; Khan, J.; Ahmed, I.; Zaidi, A.K.; Bhutta, Z.A. Effect of provision of daily zinc and iron with several micronutrients on growth and morbidity among young children in [akistan: A cluster-randomised trial. Lancet 2013, 382, 29–40. [Google Scholar] [CrossRef]
- Esan, M.O.; van Hensbroek, M.B.; Nkhoma, E.; Musicha, C.; White, S.A.; Ter Kuile, F.O.; Phiri, K.S. Iron supplementation in hiv-infected malawian children with anemia: A double-blind, randomized, controlled trial. Clin. Infect Dis. 2013, 57, 1626–1634. [Google Scholar] [CrossRef] [PubMed]
- Gera, T.; Sachdev, H.P. Effect of iron supplementation on incidence of infectious illness in children: Systematic review. BMJ 2002, 325, 1142. [Google Scholar] [CrossRef] [PubMed]
- Kortman, G.A.; Boleij, A.; Swinkels, D.W.; Tjalsma, H. Iron availability increases the pathogenic potential of salmonella typhimurium and other enteric pathogens at the intestinal epithelial interface. PLoS ONE 2012, 7, e29968. [Google Scholar] [CrossRef] [PubMed]
- Imbert, M.; Blondeau, R. On the iron requirement of lactobacilli grown in chemically defined medium. Curr. Microbiol. 1998, 37, 64–66. [Google Scholar] [CrossRef] [PubMed]
- Zimmermann, M.B.; Chassard, C.; Rohner, F.; N’Goran E, K.; Nindjin, C.; Dostal, A.; Utzinger, J.; Ghattas, H.; Lacroix, C.; Hurrell, R.F. The effects of iron fortification on the gut microbiota in African children: A randomized controlled trial in Cote d’lvoire. AJCN 2010, 92, 1406–1415. [Google Scholar] [CrossRef] [PubMed]
- Jaeggi, T.; Kortman, G.A.; Moretti, D.; Chassard, C.; Holding, P.; Dostal, A.; Boekhorst, J.; Timmerman, H.M.; Swinkels, D.W.; Tjalsma, H.; et al. Iron fortification adversely affects the gut microbiome, increases pathogen abundance and induces intestinal inflammation in Kenyan infants. Gut 2015, 64, 731–742. [Google Scholar] [CrossRef] [PubMed]
- Mwangi, M.N.; Maskey, S.; Andang, O.P.E.; Shinali, N.K.; Roth, J.M.; Trijsburg, L.; Mwangi, A.M.; Zuilhof, H.; van Lagen, B.; Savelkoul, H.F.; et al. Diagnostic utility of zinc protoporphyrin to detect iron deficiency in kenyan pregnant women. BMC Med. 2014, 12, 229. [Google Scholar] [CrossRef] [PubMed]
- WHO. Fact Sheet: World Malaria Report 2016. Available online: http://www.who.int/malaria/media/world-malaria-report-2016/en/ (accessed on 27 February 2017).
- FFI. Food Fortification Initiative. Country Profiles. Available online: http://www.ffinetwork.org/country_profiles/index.php (accessed on 27 February 2017).
- GINA-WHO. Effectiveness of Selling Micronutrient Powders (Sprinkles) in Western Kenya—NICHE Project—Multiple Micronutrient Powder (point-of-use fortification)—Infants and Young Children. Available online: https://extranet.who.int/nutrition/gina/en/node/6062 (accessed on 27 February 2017).
- Troesch, B.; van Stuijvenberg, M.E.; Smuts, C.M.; Kruger, H.S.; Biebinger, R.; Hurrell, R.F.; Baumgartner, J.; Zimmermann, M.B. A micronutrient powder with low doses of highly absorbable iron and zinc reduces iron and zinc deficiency and improves weight-for-age Z-scores in South African children. J. Nutr. 2011, 141, 237–242. [Google Scholar] [CrossRef] [PubMed]
|Age Group||Algeria||Egypt||Côte d’Ivoire||The Gambia||Ghana||Kenya||Malawi ||Morocco||South Africa |
|Children below 5||64 ||51 ||27 ||64 ||75 ||51 ||73 ||NA||66 ||NA||46 ||21 ||73||NA||30 ||NA||10.5||11|
|Child-bearing age women||NA||NA||39 ||51 ||54 ||17 ||60 ||NA||42 ||16 ||NA||NA||46||NA||33 ||NA||23||15|
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