Anemia is a health condition characterized by a reduced number of red blood cells (RBCs) or a lower-than-normal concentration of hemoglobin (Hb) within the RBCs. Hb is a protein structure responsible for carrying oxygen in high concentrations in RBCs. Deficits in either RBC count or Hb concentration decrease the blood’s capacity to carry oxygen to the body’s tissues, potentially leading to both physical and neurocognitive impairment over time.
Causes of Anemia
Multiple causes contribute to the overall global burden of anemia, with consequent implications for treatment and diagnostics (see figure below).
Types of Anemia
Estimates of disease burden by type of anemia are difficult to calculate due to challenges in attribution to a single cause, because of both diagnostic limitations and frequent concurrent etiologies.
Click here to learn more about the challenges of understanding the causes of anemia.Anemia burden by type for WRA
Hb content of the blood is lower than normal due to deficiency in one or more essential nutrients. Nutrient deficiency results from inadequate dietary intake, increased nutrient losses, impaired absorption, or altered nutrient metabolism.
Repeated infections and acute or chronic inflammation, such as celiac disease, can also decrease the absorption of nutrients and contribute to nutritional anemia.
Some of the most important nutrient deficiencies include:
- Iron deficiency
- Vitamin A deficiency
- Vitamin B-12 deficiency
- Folic acid deficiency
- Other nutritional absorption or intake issues (Vitamins C, E, B-2 B-6; zinc, copper)2Fishman SM, Christian P, West KP. The role of vitamins in the prevention and control of anaemia. Public Health Nutr. 2000;3(2):125-50. Accessed September 24, 2021. https://doi.org/ 10.1017/s1368980000000173
Iron deficiency anemia (IDA) is the most common form of nutritional anemia. An imbalance in iron intake, stores, or retention causes IDA, leaving the body unable to fully support the production of RBCs. IDA accounts for most anemia cases worldwide (approximately 60 percent of all cases
Iron shortfalls take two primary forms:
- Absolute iron deficiency: Caused by a decrease in iron stores in the body (largely in macrophages and hepatocytes). This type of iron depletion may occur in instances of increased demand, decreased intake, malabsorption, or chronic blood loss.
- Functional iron deficiency: Poor iron mobilization from stores for circulation and use in erythropoiesis. This can occur in response to elevated hepcidin levels from chronic inflammation or during situations of increased RBC production that result in a mismatch between iron demand and supply.,4Cappellini MD, Musallam KM, Taher AT. Iron deficiency anemia revisited. J Intern Med. 2019;287(2):153-170. Accessed September 23, 2021. https://doi.org/10.1111/joim.130045Nairz M, Theurl I, Wolf D, Weiss G. Iron deficiency anemia or anemia of inflammation? Wien Med Wochenschr. 2016;166(13-14):411-423. Accessed September 23, 2021. https://doi.org/10.1007/s10354-016-0505-7
Gender and Poverty as Risk Factors
This Exemplars in Global Health project focuses on a population that is of particular concern in the campaign against anemia: women of reproductive age, or WRA, in low- and middle-income (LMIC) settings.Women are both at higher risk of anemia and more sensitive to anemia as a risk factor for further medical complications, compared to men. Although rates of anemia among males improve by the end of puberty, rates of anemia among females worsen.
Income level is also a major predictor of anemia burden. It can serve as a proxy for resources and education level as they pertain to food security, healthy dietary practices, home and societal environment, and access to and use of health services.
Gender as a Risk Factor
Women are at higher risk of anemia. This is partly biological, because menstruation and pregnancy sharply elevate the risk of developing anemia.
Because of blood loss during menstruation, women have lower iron stores and hemoglobin levels, making them more susceptible to anemia and its associated adverse outcomes.
During pregnancy, a woman’s need for folate and iron increases, with the demand for iron increasing by up to threefold.
Pregnancy and birth also increase the risk of blood loss or hemorrhage, which can contribute to anemia.
Required iron intake for men and women, by age
There is significant intergenerational risk of anemia among WRA on infant health. In addition, a mother’s anemia poses serious risks for her child, both in utero and during infancy. Anemia among WRA has been linked to poor fetal growth, preterm birth, low birthweight, and perinatal mortality.
In particular, iron deficiency anemia in mothers has been linked to poor hematological parameters in their newborns, including decreased iron stores, hemoglobin levels, and serum ferritin levels.
The World Health Organization (WHO) recommends delayed umbilical cord clamping – no earlier than one minute after birth – to improve hematological and nutrition parameters for newborns, especially in anemia burdened regions.
Maternal and fetal outcomes of anemia linked by intergenerational transfer
Poverty and Food Insecurity as a Risk Factor
LMICs are disproportionately affected by anemia; for some countries, the prevalence of anemia among WRA is as high as 50 percent.
Age-standardized DALY rates for each location by SDI, both sexes combined, 2019
Poverty increases the odds of anemia in a variety of ways, from increased food insecurity to poor sanitation to reduced access to health services. Perversely, anemia also increases the odds of poverty. A child whose development is impaired by anemia among WRA may be at a lifelong disadvantage in gaining adequate education and employment. But even among adults experiencing anemia for the first time, productivity can suffer due to the reduced oxygen transport that is associated with anemia of any cause.
The Scale of the Challenge among WRA
Implications for Society
For society, anemia among WRA is associated with:
- Economic losses: Iron-deficiency anemia, which accounts for approximately 60 percent of global burden by some estimates, leads to US$16.78 total productivity losses per capita per year (4 percent of GDP) from both physical and cognitive losses.28Horton S, Ross J. The economics of iron deficiency. Food Policy. 2003;28(1):51-75. https://doi.org/10.1016/S0306-9192(02)00070-2
- Preventable negative health outcomes: Based on 10-year investment projections from 2016 through 2025, reaching the World Health Assembly target of 50 percent reduction in anemia (compared to 2012 levels) would prevent an additional 265 million cases of anemia among WRA, 800,000 child deaths, and 7,000 to 14,000 maternal deaths.29Shekar M, Kakietek J, Eberwein JD, Walters D. An Investment Framework for Meeting the Global Nutrition Target for Anemia. World Bank Group. 2017. http://documents1.worldbank.org/curated/en/244081491391841079/pdf/114022-BRI-Anemia-rev-v5-WEB-PUBLIC.pdf
Prevalence of anemia, 2019; % of women of reproductive age (WRA, 15-49 y.o.); Source: IHME. Global Burden of Disease. 2019.
Diagnosing Anemia
Anemia is diagnosed formally based on the concentration of Hb in a blood sample. WHO sets the cutoffs for mild, moderate, and severe anemia.
Several other supplemental tests can help specify an anemia diagnosis, such as tests of biomarkers like serum ferritin or hematocrit concentration.
In low-resource settings where blood or biomarker tests are difficult to administer, health care workers can diagnose anemia based on symptoms and contextual factors: reviewing symptoms of anemia such as fatigue or weakness and considering the context around risk of anemia such as pregnancy status and diet.
Click here to learn more about the challenges of diagnosing anemia.Strategies for Anemia Control
Although anemia can be a very dangerous condition, it is also both preventable and treatable. Several interventions focus on nutrition. These fall into a few broad categories.
Direct Interventions
| Direct Health Care Sector Nutritional Interventions |
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Supplementation Iron plus folic acid supplementation (IFA) is a widely used measure for preventing iron deficiency and anemia by providing essential micronutrients during pregnancy. Antenatal multiple-micronutrient supplementation (which includes IFA along with additional nutrients) has a similar effect on anemia to IFA alone, but is associated with even better birth outcomes. 32 Haider BA, Bhutta ZA. Multiple-micronutrient supplementation for women during pregnancy. Cochrane Database Syst Rev. 2017;4(4):CD004905. Accessed September 25, 2021. https://doi.org/10.1002/14651858.CD004905.pub5 33 Sudfeld CR, Smith ER. J Nutr. 2019;149(3):359-361. Accessed September 25, 2021. https://doi.org/10.1093/jn/nxy279 34 World Health Organization. Iron with or Without Folic Acid Supplementation in Women. World Health Organization; 2019. Accessed September 25, 2021. https://www.who.int/elena/titles/full_recommendations/ifa_supplementation/en/ 26 Sunuwar DR, Singh DR, Chaudhary NK, Pradhan PMS, Rai P, Tiwari K. Prevalence and factors associated with anemia among women of reproductive age in seven South and Southeast Asian countries: evidence from nationally representative surveys. PLoS One. 2020;15(8):e0236449. Accessed October 5, 2021. https://doi.org/10.1371/journal.pone.0236449 35 Falkingham M, Abdelhamid A, Curtis P, Fairweather-Tait S, Dye L, Hooper L. The effects of oral iron supplementation on cognition in older children and adults: a systematic review and meta-analysis. Nutr J. 2010;9:4. Accessed September 25, 2021. https://doi.org/10.1186/1475-2891-9-4 IFA comes in numerous forms, including pills, capsules, drops, and extended-release tablets. The average cost for IFA is about US$1 per pregnancy. 36 World Health Organization. Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity. World Health Organization; 2011. WHO/NMH/NHD/MNM/11.1. Accessed October 5, 2021. https://www.who.int/vmnis/indicators/haemoglobin.pdf |
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Intravenous iron therapy Intravenous (IV) therapy delivers a high dose of iron in a single infusion, as an acute treatment for moderate and severe anemia. IV iron is superior to oral iron for treatment of iron deficiency anemia. 37 Qassim A, Grivell RM, Henry A, Kidson-Gerber G, Shand A, Grzeskowiak LE. Intravenous or oral iron for treating iron deficiency anaemia during pregnancy: systematic review and meta-analysis. Med J Aust. 2019;211(8):367-373. Accessed September 25, 2021. https://doi.org/10.5694/mja2.50308 38 Qunibi WY. The efficacy and safety of current intravenous iron preparations for the management of iron-deficiency anaemia: a review. Arzneimittelforschung. 2010;60(6a):399-412. Accessed October 5, 2021. https://doi.org/10.1055/s-0031-1296304 |
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Inflammation and infection control Malaria prevention programs, including residual indoor spraying and long-lasting bed nets for WRA, as well as intermittent preventative treatment in pregnancy, can reduce malarial anemia. 39 White NJ. Anaemia and malaria. Malar J. 2018;17(371). Accessed October 5, 2021. https://doi.org/10.1186/s12936-018-2509-9 40 Smith JL, Brooker S. Impact of hookworm infection and deworming on anaemia in non-pregnant populations: a systematic review. Trop Med Int Health. 2010;15(7):776-795. Accessed October 5, 2021. https://doi.org/10.1111/j.1365-3156.2010.02542.x 41 Girum T, Wasie A. The effect of deworming school children on anemia prevalence: a systematic review and meta-analysis. Open Nurs J. 2018;12:155-161. Accessed October 5, 2021. https://doi.org/10.2174/1874434601812010155 |
| Other Sectoral Nutrition Interventions |
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Education and sociocultural practices in dietary diversity A varied diet provides sufficient iron for most of the population. The main nutrients of concern for nutritional anemia are iron, vitamin A, vitamin B12, and folate. Increasing knowledge and adjusting diet practices around diet during pregnancy or diet differences between men and women, such as the consumption of animal sourced foods, can help to meet nutrient requirements and prevent anemia. |
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Large-scale food fortification Mass fortification of staple foods involves the addition of one or more micronutrients to address vitamin and mineral deficiencies at the population level. Folic acid, Vitamin A, and iron can be added to foods such as maize, flour, rice, milk, and other food products to help address anemia within a population. 42 Bailey RL, West KP, Black RE. The epidemiology of global micronutrient deficiencies. Ann Nutr Metab. 2015;66(Suppl 2):22-33. Accessed September 25, 2021. https://doi.org/ 10.1159/000371618 43 Keats EC, Neufeld LM, Garrett GS, Nmuya MNN, Bhutta ZA. Improved micronutrient status and health outcomes in low- and middle-income countries following large-scale fortification: evidence from a systematic review and meta-analysis. Am J Clin Nutr. 2019;109(6):1696-1708. https://doi.org/10.1093/ajcn/nqz023 |
Indirect Interventions
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Reproductive health Interventions that improve the pregnancy-related burden of anemia include adequate birth spacing, reduced early-pregnancy rates, improved parity, and increased availability of emergency obstetric care. 44 Masukume G, Khashan AS, Kenny LC, Baker PN, Nelson G; SCOPE Consortium. Risk factors and birth outcomes of anaemia in early pregnancy in a nulliparous cohort. PLoS One. 2015;10(4):e0122729. Accessed October 5, 2021. https://doi.org/10.1371/journal.pone.0122729 45 King, JC. The risk of maternal nutritional depletion and poor outcomes increases in early or closely spaced pregnancies. J Nutr. 2003;133(5):1732S-1736S, https://doi.org/10.1093/jn/133.5.1732S 46 Fischer JAJ, Sasai CS, Karakochuk CD. Iron-containing oral contraceptives and their effect on hemoglobin and biomarkers of iron status: a narrative review. Nutrients. 2021;13(7):2340. Accessed October 5, 2021. https://doi.org/10.3390/nu13072340 |
| Indirect Other Sectoral Interventions |
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Agricultural interventions Improvements in the security, accessibility, and affordability of food can provide the underlying context for improved dietary diversity. Agricultural improvements can additionally improve the yield and nutrient content of foods. 47 Hefferon KL. Nutritionally enhanced food crops; progress and perspectives. Int J Mol Sci. 2015;16(2):3895-3914. Accessed October 5, 2021. https://doi.org/10.3390/ijms16023895 |
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Biofortification Biofortification efforts genetically modify crops to have higher nutrient content, including boosting the iron in staple foods such as beans, lentils, and sorghum. This provides a long-term intervention with low recurring costs. 48 HarvestPlus. Breeding Crops for Better Nutrition. HarvestPlus; 2006. Accessed September 25, 2021. https://www.harvestplus.org/sites/default/files/brochure.pdf |
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Water, sanitation, and hygiene improvement These measures include clean water, sanitation programs, and public education on sound hygiene. Such measures can reduce infection-driven burden, reduce chronic inflammation, and improve overall household health environment. 49 Fançony C, Soares Â, Lavinha J, Barros H, Brito M. Efficacy of nutrition and WASH/malaria educational community-based interventions in reducing anemia in preschool children from Bengo, Angola: study protocol of a randomized controlled trial. Int J Environ Res Public Health. 2019;16(3):466. Accessed October 5, 2021. https://doi.org/10.3390/ijerph16030466 50 Nounkeu CD, Dharod JM. Integrated approach in addressing undernutrition in developing countries: a scoping review of integrated water access, sanitation, and hygiene (WASH) + nutrition interventions. Curr Dev Nutr. 2021:5(7):nzab087. Accessed October 5, 2021. https://doi.org/10.1093/cdn/nzab087 |
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Social determinants of health Education and empowerment programs for girls and women can help increase health and nutrition literacy; improve gender equality in marriages; encourage equitable access to food and health services; and shift cultural norms away from early pregnancies and short birth spacing. 51 De-Regil LM. Transforming the lives of women and adolescent girls through anaemia prevention. Nutrition International; 2017. Accessed October 5, 2021. https://www.nutritionintl.org/news/all-blog-posts/transforming-lives-women-adolescent-girls-anaemia-prevention/ 52 Roshan FSN, Navipor H, Alhani F. The effect of education-based intervention using small group discussion in empowering adolescent girls to prevent iron deficiency anemia. Patient Saf Qual Improv. 2014;2(4):151-155. Accessed October 5, 2021. https://psj.mums.ac.ir/article_3399_e716d1888007207fad564c1730be686a.pdf 53 Gupta S, Pingali P, Pinstrup-Andersen P. Women’s empowerment and nutrition status: The case of iron deficiency in India. Food Policy. 2019:88(101763). Accessed October 5, 2021. https://doi.org/10.1016/j.foodpol.2019.101763 |
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Economic determinants of health Poverty reduction, in particular income-generating programs for women, can help provide household and societal environments that are conducive to the successful prevention and treatment of a wide range of health problems, such as through improved food security and nutrition interventions for anemia. In addition, economic welfare provides more opportunities for access to health care services. |
