Alexandria Kristensen-Cabrera is the lead author and who organized the case study through interviews with Dr. Juan Pablo Peña-Rosas, who provided substantial additions to the case study. Dr. Luis Gabriel Cuervo, who as a mentor provided guidance and inspiration, reviewed and edited the final drafts. Ruben Grajeda, Michele Gilbert, and Louisa Stuwe were the external reviewers of the case study. Louisa Stuwe has translated the case study into Spanish, reviewed by María Medina. Christopher Khanoyan assisted with the format. The photo illustrating the case study belongs to the exhibition "Research in Motion" by photographer Jane Isabelle Dempster and is part of PAHO's "Art for Research" project (www.paho)
What is the problem?
It is estimated that about half of the anemia in the population is due to iron deficiency . Although iron deficiency is the most common cause, other vitamin and mineral deficiencies, chronic inflammation, parasitic infections, and inherited disorders can cause anemia. Both anemia and iron deficiency have serious consequences for health and financially.
نقص الحديد عند الاطفال
Iron deficiency anemia compromises the child's ability to learn, which further limits his future prospects which, in aggregate terms, hinders the development of the population.
The most recent estimates from the World Health Organization (WHO) suggest that anemia affects around 800 million children and women. In fact, 528.7 million women and 273.2 million children under the age of 5 were anemic in 2011, and about half of them were also iron deficient.  Malnutrition and micronutrient malnutrition have serious economic consequences, costing an estimated US $ 1.4-2.1 trillion or 2.3 percent of the world's gross domestic product (GDP) per year. According to Bailey RL et al. ii, investing in the prevention and treatment of micronutrient malnutrition results in improved health status, a reduction in infant and maternal mortality, and better outcomes with a "cost-benefit ratio" of nearly 1 to 13. [2 ].
The estimated distribution of the prevalence of anemia for infants / children and pregnant women is illustrated in Figure 1.
Iron deficiency is the world's most widespread micronutrient deficiency often resulting in chronic iron deficiency or iron deficiency anemia (defined by the World Health Organization (WHO) as hemoglobin levels of = 11 g / dl )  . Cutoffs vary based on age, gender, altitude, smoking status, and pregnancy status. 1
To regenerate iron stores, men need 0.9 mg, women of childbearing age require 1.3 mg, and pregnant women require 3.0 mg per day of iron. High iron intake is also required for growth. Another estimate from the University of Toronto found that the total loss (cognitive and physical) due to iron deficiency is around 4.05% of GDP per year, while physical losses are only around 0.57% of the GDP (calculated on the basis of 10 developing countries). 
Anemia in pregnancy has numerous health effects for the baby including an increased risk of growth retardation, blindness, serious illness, decreased cognitive performance, and spinal and brain defects. Anemia in pregnancy also increases the risk of miscarriage, stillbirth and low birth weight thus increasing the risk of infant mortality, as well as complications in childbirth causing hemorrhages that correspond to an increased risk of depression and maternal mortality  . Iron deficiency anemia contributes to an estimated 115,000 maternal deaths / year worldwide. Infants and young children with iron deficiency anemia are more likely to have attention deficits, reduced motor coordination, and language difficulties  . For school-age children, this type of anemia also decreases school participation  . There is strong evidence showing that iron treatment for school-age children can improve test scores of cognitive ability and educational achievement. 5
Research in practice
It is important to address the causes of iron deficiency. Iron deficiency can be the result of unmet needs (pregnancy, growth, improper diet), and / or increased losses (chronic inflammation, parasitic infections).
One way to supplement the diet is iron fortification by fortifying staple foods, such as wheat flour, corn flour, or rice with iron and other vitamins and minerals. Some seasonings, such as fish sauce and soy sauce, have also been fortified with iron. Studies have shown that iron fortification corresponds to a reduction in the prevalence of anemia. 9.10For example, the Food Fortification Initiative found evidence to suggest that, "although this type of evidence precludes a definitive conclusion," the prevalence of anemia has decreased significantly in countries that use micronutrient fortification of flour, while not it has changed in countries that do not  .
A study looking at the effects of iron fortification on wheat and cornmeal showed that fortification had a 'protective effect' against gestational anemia (the study included 778 women)  . Corn flour fortification can improve nutritional status if it is mandated at the national level in countries where these staples are frequently consumed.  . High sensory acceptability has been found for a number of iron fortifiers.  , Two Cochrane reviews are pending on the effects of fortifying corn flour, wheat flour and rice with iron and other vitamins and minerals for the prevention of anemia and other health problems and nutritional outcomes  ,  ,  . There is also a review on the bioavailability of the different iron compounds used in food fortification. 
Image 1. Institute of Nutrition of Central America and Panama Children receive breakfast, lunch and two snacks per day, a diet instituted by INCAP nutritionists who monitor the development of children.
Another option to prevent and treat anemia is iron supplementation. This is an effective technique, even as a preventive method to reduce the probability of maternal anemia in pregnant women. An intervention in rural areas of Vietnam measured the effects of iron supplementation and iron-fortified milk on hemoglobin status in pregnant women.  The study found that "hemoglobin concentrations in both treatment groups were not significantly different," but hemoglobin levels were lower in the iron supplemented comparison groups. 
Iron fortification is a low-cost intervention: the cost of iron fortification of wheat flour is often less than 1% of the wholesale cost or less than US $ 1.00 per metric ton. For this reason, this mechanism is very profitable: US $ 4.40 / disability-adjusted life year (DALY) for the fortification of iron flour compared to US $ 12. 80 / DALY for iron supplementation and US $ 29.00 / DALYs for vitamin A fortification . 
Excessive iron intake or overload can be harmful, potentially leading to iron overload and blood disorders.  However, iron overload due to extended intake of extended iron supplements or flour fortification is very rare.  , , 24 Possible side effects of iron overload include diarrhea, constipation, and nausea at higher doses. 
What is the next step?
In order to implement efficient and feasible strategies for iron fortification as a solution to iron deficiency anemia, it is important that each country address the recommendations of iron nutrition experts and WHO in a systematic way, including legislation and regulations. research, bioavailability and supply of iron fortification, educating the population about iron deficiency, and conducting trials with individuals using clinical pathways to measure plasma or serum ferritin concentration as an index of iron deficiency and overload, as seen in figures 3 and 4. [25 ]
There are three main types of fortification recognized by the WHO: commercial, universal, and aimed at high-risk populations  . Universal iron fortification, when no unenriched options are available, potentially puts those with hemochromatosis (caused by increased iron intake) at greater risk of iron overload. Therefore, market-driven or directed approaches are often favored 22 . The highest risk groups are pregnant women, infants, and school-age children.
While there is substantial evidence of the efficacy of iron fortification and supplementation in reducing iron deficiency anemia, benefits are hampered by low utilization of preventive health services in developing countries, lack of infrastructure and the national political unity for the large-scale enrichment of popular local foods, and the incomplete enactment of preventive treatments. Addressing these barriers with research is critical to effectively preventing iron deficiency anemia. 
Figure 3. Clinical pathway for iron deficiency
Figure 4. Clinical pathway for iron overload
According to a review of the iron fortification of wheat flour, "most of the current iron fortification programs are likely to be ineffective. Legislation needs to be updated in many countries so that the flour is fortified to adequate levels. Of recommended iron compounds [28 ] Therefore, countries where flour is an ingredient in staple foods should comply with the WHO recommendations on levels of iron fortification in wheat and maize flour.  It is important for countries to fortify staple foods in their respective countries.
Quality and targeted research is a critical component in addressing iron deficiency anemia. "Despite the high incidence and disease burden associated with this condition, there is a paucity of good quality trials evaluating the clinical maternal and neonatal effects of iron administration in women with anemia ... variable or inadequate reports trial data that can inform health equity decisions may contribute to research waste and not serve the needs of people affected by health inequalities  . Therefore, it is crucial to implement research strategies with solid parameters that allow valid results that are comparable between countries and that address equity in health (absence of avoidable and unfair differences in health). According to the PAHO policy on Research for Health (CD49.R10) , all activities to improve health must be based on evidence, in order to contribute to the strengthening of public health with greater efficiency and better results. health care.
Two studies supported by WHO / PAHO conducted in 2015 are paving the way:
Figure 5. CONSORT- Equity: study phases
An effective way to address the lack of iron supply and the bioavailability of iron in the diet is iron fortification  . Iron fortification can help reduce iron deficiency anemia, which may have positive developmental effects among populations, including improved cognitive and academic performance, as well as decreased child birth defects, rates of maternal and infant mortality. Improved cognitive and academic performance as well as fewer days absent from school can translate into a better-trained workforce resulting in financial gains. The decrease in negative health effects leads to a reduction in healthcare costs. In summary, there is potential for efficient and viable conquest of iron deficiency and lack of iron supply did can result in improved health and development.