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What is anemia?

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.1

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)2

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 cases3 ), though etiological estimates are difficult to establish. Although IDA rarely causes death, it can cause serious health conditions, especially among women and children, who represent most of global anemia burden.

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.4,5

 

Many diseases cause anemia through multiple mechanisms, including disease-specific loss or destruction of RBCs, altered RBC production, infection-induced malabsorption of iron or other nutrients, and infection-associated inflammation. Chronic inflammation, as observed in certain diseases such as inflammatory bowel disease, also increases the risk of anemia by causing elevated levels of the protein hepcidin (which suppresses iron absorption into the body).6

Reducing the incidence of disease is critical to minimizing the risk of anemia – from direct treatment and care (e.g., intermittent preventative treatment of malaria during pregnancy) to improved household environment (e.g., sanitation). Some of the diseases presenting the highest risk of anemia include:

  • Malaria
  • Schistosomiasi
  • HIV/AIDS
  • Hookworm disease
  • Chronic inflammation

 

Genetic structural variation or reduced production of globin chains of Hb can result in anemia through subfunctional or nonfunctional RBC production.7

Furthermore, in low- and middle-income countries (LMICs), screening for genetic disorders does not always occur with sufficient regularity. Some of the genetic conditions commonly related to the onset of anemia include:

  • Sickle cell disorders 
  • Thalassemias
  • G6PD deficiency
  • Other hemoglobinopathies

   

Several other chronic, noncommunicable diseases and conditions can lead to anemia through blood loss, interruption of RBC production, or insufficient nutrient uptake and absorption.8 Several types of endocrine, metabolic, blood, immune, and other disorders fall into this category:

  • Chronic kidney disease
  • Inflammatory bowel disease
  • Gastritis and duodeniti
  • Peptic ulcers
  • Other chronic diseases

   

Women of reproductive age (WRA) and pregnant woman are at higher risk of bleeding, which can lead to anemia because the blood and RBCs lost take time and nutrients to replace.

Women with uterine fibroids, other gynecological diseases, or heavy menstrual flow are at higher risk of anemia.

Further, pregnancy raises the risk of developing anemia, first due to increased demands of the body for RBCs during gestation and second due to the risk of hemorrhage during birth.

  • Maternal hemorrhage
  • Uterine fibroids
  • Other gynecological diseases

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.9 Additionally, during pregnancy, anemia poses intergenerational health risks.

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.10,11,12,13 Hemodilution occurs in all pregnancies as blood plasma volume increases at a faster relative rate than blood contents.14 Thus, RBC needs often increase faster than the body’s production rate, leading to anemia.

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

Women are more sensitive to anemia as a risk factor for further medical complications. If her RBC levels fall too low and she becomes severely anemic, a pregnant woman will become more vulnerable to a range of detrimental outcomes, from depression to placental disruption to higher risk of mortality due to postpartum hemorrhage. Anemic pregnant women are also more likely to be admitted to the intensive care unit.15,16

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.17 It can also carry adverse effects for fetal and young-infant brain development – a deficit not captured when measuring the years of healthy life lost due to disability (YLDs) caused by anemia.

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.18 Iron deficiency anemia in infancy negatively influences performance in tests of psychomotor development.19 Even after repletion, iron deficiency anemia in infancy has been associated with reduced cognitive function as many as ten years later.20

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.21,22

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.23 Women in LMICs are at especially high risk of developing anemia and suffering from its related consequences.24,25,26

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.27

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.28
  • 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.29

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.30,31

Direct Interventions
Direct Health Care Sector Nutritional Interventions

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.32,33   Daily or weekly IFA is also recommended by WHO in settings where prevalence of anemia is high.34,26 A meta-analysis reported that iron supplementation was associated with higher attention and concentration in children, adolescents, and women.35   IFA is also recommended for adolescent girls to prevent anemia development. Note that this varies by region.

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 

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   Given this and the continued challenges in delivery and adherence to iron supplements, IV iron is an attractive treatment option for anemia. For example, it could be administered as part of routine antenatal and postpartum care at a single visit. However, IV therapy remains less widely administered than iron supplementation, and carries risk of adverse reaction.38  

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 Deworming programs can also help address other common infection-driven anemias.40,41  HIV prevention programs reduce the burden of HIV-related anemia.
Other Sectoral Nutrition Interventions

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.  

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 In a systematic review of evidence, large-scale food fortification increased serum micronutrient concentrations with a 34 percent reduction in anemia.43  

Indirect Interventions

 
Indirect Health Care Sector Interventions

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.44,45  Menstrual and gynecological interventions, such as improved access to contraception, can also reduce bleeding-related risks.46 
Indirect Other Sectoral Interventions

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  

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  

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.49,50

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.51,52,53 

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. 
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