Iron deficiency occurs when there is an insufficient intake of iron—primarily found in flesh foods and, to a lesser extent, dairy products and plant foods—as well as in fortified foods or supplements. Iron deficiency can also be caused by poor absorption and excessive loss of the mineral, including blood loss. The more severe stages of iron deficiency can result in anemia when there is not enough iron to produce adequate amounts of hemoglobin for red blood cells (WHO and CDC 2004). Iron deficiency is a major contributor to anemia, though the actual extent of overlap between iron deficiency and anemia is context-specific and varies by setting (Kassebaum and GBD 2013 Anemia Collaborators 2016). Specific groups at an increased risk of iron deficiency include children (due to rapid growth), pregnant women (due to expansion of the red blood cell mass and the need for more iron for the fetus), and women of reproductive age, including adolescent girls (due to blood loss during menstruation).
How is iron deficiency measured?
Bone marrow aspirates are the gold standard for assessing iron deficiency, but this method is not practical for population-based measurements. Ferritin is the most commonly used biomarker for iron status; the World Health Organization (WHO) recommends the use of ferritin to assess iron status in population-based surveys. Ferritin measures the amount of iron stores in the body; low levels reflect depleted iron stores. Serum transferrin receptors (sTfR), which reflect the need for iron at the cellular level, is also a biomarker used to assess iron status (WHO 2011).
Ferritin and sTfR levels can be determined using a venous or capillary blood sample and require maintaining a cold chain. Laboratory assessments commonly include enzyme-linked immunosorbent assay (ELISA), immunoturbidimetry, or others (WHO and CDC 2004).
How is iron deficiency categorized?
A definition for what constitutes a public health problem for iron deficiency has not been established. Table 4 describes the cut-offs for defining iron deficiency using ferritin, with differences based on age and pregnancy status.
Table 4: Iron Deficiency Cut-offs Based on Serum Ferritin Concentration
|Serum Ferritin (mcg/l)|
|Less than 5 years of age||Five years of age or older|
|Depleted iron stores||<12
(where infection and inflammation are not prevalent)
(in areas where infection and inflammation are not prevalent)
|Depleted iron stores in presence of infection||<30||<30||-||-|
|Severe risk of iron overload (adults)||-||-||>200||>150|
Where can we get these data?
Iron deficiency is measured in population-based surveys and research studies, among women of reproductive age and children. Of the commonly administered population-based surveys, the National Micronutrient Survey is usually the only one that collects and analyzes information on the prevalence of iron deficiency.
- While the prevalence of anemia is sometimes used as a proxy indicator for iron deficiency, this poses many problems, because iron deficiency is only one of many causes that lead to anemia and, depending on the setting, may not even be a major contributor (Kassebaum et al. 2014). Additionally, mild and moderate levels of iron deficiency may not manifest as anemia, although they probably still result in functional impairment (WHO 2001).
- Infection and inflammation can increase ferritin concentrations, which can complicate the interpretation of iron status using ferritin concentrations. In addition to being a biomarker of iron status, ferritin concentrations are also a positive acute phase protein and they rise in response to inflammation. In other words, ferritin levels may be elevated in the presence of inflammation, irrespective of iron status, and may lead to an underestimation of the prevalence of iron deficiency.
- Approaches have been developed to adjust ferritin concentrations for inflammation using the inflammation biomarkers alpha-1-acid-glycoprotein and C-reactive protein. The four types of approaches currently proposed are to—
- Exclude individuals with elevated inflammation from calculations of iron status (WHO and CDC 2004),
- Raise the ferritin threshold to <30 mcg/l for those with elevated inflammation (WHO and CDC 2004),
- Use a categorical correction factor (Thurnham et al. 2010),
- Use a regression correction (Namaste et al. forthcoming).
Verify if any adjustment approach was used to determine iron deficiency when using ferritin concentrations. If it was not used, note this in your limitations and recognize that iron deficiency is probably a bigger problem than your data indicates. If you have the raw data available, apply these adjustments. Present both adjusted and unadjusted prevalence levels.
- As an alternate to using adjustment approaches, in areas with a high prevalence of inflammation, you can use the combination of ferritin and sTfR. This method may help you determine if iron deficiency is a problem in your setting by using the definition in Table 5.
Table 5: Interpretation of Serum Ferritin and Transferrin Receptor Concentrations in Population Surveys
|Percentage of Serum Ferritin Values Below Thresholda||Percentage of Serum Transferrin Receptor Above Cut-Off Valuesb||Interpretation|
|<20c||<10||Iron deficiency not prevalent|
|<20c||≥10||Iron deficiency prevalent|
|≥20d||<10||Iron deficiency prevalent|
Erhardt, Juergen G., John E. Estes, Christine M. Pfeiffer, Hans K. Biesalski, and Neal E. Craft. 2004. “Combined Measurement of Ferritin, Soluble Transferrin Receptor, Retinol Binding Protein, and C-Reactive Protein by an Inexpensive, Sensitive, and Simple Sandwich Enzyme-Linked Immunosorbent Assay Technique.” The Journal of Nutrition 134 (11): 3127–32.
Kassebaum, Nicholas J. 2016. “The Global Burden of Anemia.” Hematology/Oncology Clinics of North America 30 (2): 247–308. doi:10.1016/j.hoc.2015.11.002.
Kassebaum, Nicholas J., Rashmi Jasrasaria, Mohsen Naghavi, Sarah K. Wulf, Nicole Johns, Rafael Lozano, Mathilda Regan, et al. 2014. “A Systematic Analysis of Global Anemia Burden from 1990 to 2010.” Blood 123 (5): 615–24. doi:10.1182/blood-2013-06-508325.
Namaste, Sorrel ML, Grant J. Aaron, Ravi Varadhan, Janet M. Peerson, and Parminder S. Suchdev. Forthcoming. “Methodological Approach for the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) Project.”
Thurnham, David I., Linda D. McCabe, Sumanto Haldar, Frank T. Wieringa, Christine A. Northrop-Clewes, and George P. McCabe. 2010. “Adjusting Plasma Ferritin Concentrations to Remove the Effects of Subclinical Inflammation in the Assessment of Iron Deficiency: A Meta-Analysis.” American Journal of Clinical Nutrition 92 (3): 546–55. doi:10.3945/ajcn.2010.29284.
WHO. 2011. “Serum Ferritin Concentrations for the Assessment of Iron Status and Iron Deficiency in Populations.” WHO/NMH/NHD/MNM/11.2. Vitamin and Mineral Nutrition Information System. Geneva, Switzerland: World Health Organization. http://www.who.int/vmnis/indicators/serum_ferritin.pdf.
WHO. 2001. “Iron Deficiency Anaemia: Assessment, Prevention and Control: A Guide for Programme Managers.” Geneva, Switzerland: WHO. http://apps.who.int/iris/handle/10665/66914.
WHO and CDC. 2004. “Assessing the Iron Status of Populations : Including Literature Reviews.” 2nd ed. Joint World Health Organization/Centers for Disease Control and Prevention Technical Consultation on the Assessment of Iron Status at the Population Level. Geneva, Switzerland.