Anemia is endemic throughout the world. In 2011, 29% of nonpregnant women, 38% of pregnant women, and 43% of children aged 6–59 mo were anemic, with estimates improving only modestly since 1995 (1). Maternal anemia has serious consequences, among them increased maternal mortality, adverse birth outcomes, poor mental health and fatigue, and delayed child development (2). Anemia in children affects child development, but this is less clear in children younger than 3 y, among whom only effects on motor development are consistent (2). The most common cause of anemia is iron deficiency, and worldwide, the proportion of all anemia amenable to iron supplementation is estimated to be ~50% in nonpregnant and pregnant women and 42% in children (1).

Food fortification is described as one of the most cost-effective strategies available to improve micronutrient status, including iron status (3). A variety of food vehicles have been fortified with iron and other nutrients, and these can be grouped in 3 broad categories: staples, condiments, and processed commercial foods (4). Systematic reviews of mostly efficacy studies show that iron status improves and anemia declines when foods fortified with iron are consumed (4–6). However, evidence from national fortification programs is limited and inconsistent (7–9). In an analysis of the characteristics of 78 national wheat flour fortification programs, it was concluded that only 9 could be expected to have the desired impact; the problems identified were common use of atomized and hydrogen-reduced iron powders, which have poor bioavailability, and inadequate levels of fortification given levels of consumption of wheat flour (7). An example is Brazil, where hemoglobin levels in children remained essentially constant after fortification of wheat and maize flour became mandatory; this was attributed to the use of low bioavailability fortificants and weak enforcement mechanisms (10).

We searched for relevant data to carry out an evaluation of the national food fortification program in Costa Rica, where wheat and maize flour and liquid and powdered milk are mandated by law to be fortified with iron and other micronutrients. We use a one-group pretest-posttest design (11) to assess the impact on anemia in women and children and on iron status in children. We also identify pathways leading to impact.

Descriptive statistics are shown in Tables 2 and 3. On average, children were aged 4 y and women aged 31 y in all surveys. In 1996, the country was divided into nearly equal thirds of urban, rural, and metropolitan areas, but in 2008, the country became more urban and less metropolitan.

Hemoglobin and serum ferritin improved, whereas anemia and iron deficiency were reduced in children at national and sentinel site levels (Table 2, Supplemental Figure 1); notably, iron deficiency anemia was not detected at the endline. From a baseline mean of 12.1 g/dL in children, hemoglobin improved by 0.7 g/dL at the national level and by 0.5 g/dL in the sentinel sites (Table 2). Hemoglobin increased and anemia decreased in women (Table 3, Supplemental Figure 2). In women, the hemoglobin starting point was 12.9 g/dL, and means improved by 0.4 and 0.5 g/dL at national and sentinel site levels, respectively (Table 3). The shift to the right in hemoglobin values of women and children occurred along the entire distribution, as indicated by the test for equal densities (Supplemental Figures 3 and 4). Identical results to those in Tables 2 and 3 were obtained in models that added age, sex (children), and area of residence dummy indicator variables as covariates (results not shown). Nationally, anemia (Table 4) and iron deficiency (Supplemental Table 1) in children declined in both sexes, in urban and rural areas, and in those older and younger than 3 y. In women, anemia declined in all areas (Table 5). Declines in anemia in the sentinel sites were consistent with national declines (Tables 4 and 5, Supplemental Table 1).

Dietary data from the sentinel site sites in 2008–2009 for children were used to estimate consumption of wheat and maize flour equivalents and milk, amount of iron from fortification provided by these foods, and percentage of the EAR (Table 6). Maize flour contributed little to iron intakes; the contribution from wheat flour and milk was important and about equal. More iron was consumed in the urban site, due to greater consumption of wheat flour. Combining both sentinel sites, children obtained 3.3 mg of iron from fortification. Overall, fortification provided the equivalent of about half the EAR, with the interquartile range being 29–80%. The percentage contribution to the EAR in children aged <3 y was 54%, slightly higher than for children aged 3–7 y (47%).

Periodic monitoring showed that the iron content of fortified foods met levels mandated by law (Supplemental Table 2). Special sampling from 2008 showed that the iron content in flour samples collected in bakeries was in compliance, with little variation by county (Figure 1) and by mill and brand (Supplemental Figures 5 and 6). The mean ± SD iron content in the flour samples was 67.5 ± 8.1 mg/kg, and the mean ± SD deviation from the mandated content of 55 mg/kg was 12.0 ± 8.1 mg/kg.

We have documented a plausible impact pathway (Figure 2) that suggests that the fortification program in Costa Rica improved iron status and decreased anemia. The baseline data were collected in 1996 before the fortification program was strengthened and expanded; at that time, there was evidence of potential to benefit, as indicated by iron deficiency. Reduced iron, which has not been shown to be efficacious (7), was replaced by ferrous fumarate in wheat flour in 2002, and ferrous bisglycinate was added to maize flour in 1999 and to liquid and powdered milk in 2001. These iron compounds are fortificants with very good bioavailability and proven efficacy (7). The endline survey was conducted in 2008–2009, confidently after the program was fully matured and established. Monitoring data of the fortification program consistently showed that there was compliance with the legislation. Dietary intake data from children showed that the fortification program provided the equivalent of about half the EAR for iron, assuming 10% bioavailability. Finally, the prevalence of anemia in children and women dropped significantly nationally. Iron status improved in children but was not measured in women. At the national level, anemia in children aged <7 y was reduced from 19% to 4%, whereas in women, the decline was from 18% to 10%. In children, iron deficiency was reduced from 27% to 7%, and iron deficiency anemia was not detected at the endline.

The most likely nutrient driving the improvement in anemia is iron because of the substantial drop in iron deficiency. However, other nutrients that also improve hemoglobin (23) were provided through fortification and could have contributed to the reduction in anemia; these include vitamin A to milk and sugar; folic acid to wheat and maize flour, milk, and rice; and vitamin B-12 to rice. Helminthic infections were low, with ~2.5% of children aged 1– 7 y infected in 2008 (24), and can be dismissed as a significant cause of anemia.

It is sometimes said that young children are unlikely to benefit as much as adults from fortification because they consume smaller amounts of staple foods. However, children aged 1–3 y in Costa Rica consumed almost as much iron from fortification as did children aged 3–7 y, 2.9 and 3.5 mg/d, respectively (Table 6). Had only wheat flour been fortified with iron, only approximately one-half to one-third of these amounts would have been consumed, an indication of the value of milk as a vehicle for young children, particularly where milk is distributed to poor households as in Costa Rica. In the rural sentinel site, where the logistics of providing liquid milk are difficult, powdered milk was mostly consumed. We are uncertain as to the exact percentage of the EAR met by fortification. The EAR recommendations come from the United States, where it is assumed that 18% of the iron in the mixed diet is absorbed (21). Bioavailability is assumed to be poor (5%) where diets are primarily cereal and plant based, intermediate (10%) where some refined products and animal protein are consumed, and good (15%) in more developed countries where the diet is very low in fiber and high in animal products (22). We considered that 10% bioavailability was appropriate for Costa Rica, but perhaps this could be higher because of the use of ferrous bisglycinate, an iron–amino acid chelate with good bioavailability (25). We estimate that 54% of the EAR in children aged 1–3 y was provided by fortification compared with 47% in children older than 3–7 y (Table 6). In both age groups, these levels seem large enough relative to the probable nutrient gap to have an impact. Anemia declined nationally from 30.0% to 4.6% in children aged 1–3 y and from 15.4% to 3.7% in children aged 3–7 y (Table 4).

Fortification, particularly wheat flour fortification, has been described as an intervention more likely to benefit the better off, who have access to and can afford fortified foods (8). In Guatemala, the poorest, rural, indigenous populations with the highest burden of nutritional deficiencies likely benefit the least from wheat flour fortification because they are maize consumers (20). The solution lies in fortifying a food or a basket of foods that are consumed by the needy. Wheat flour consumption in children aged 1–7 y was twice as large in the urban compared with the rural sentinel site (Table 6); nonetheless, children aged 1–7 y obtained 2.8 mg daily iron from fortification in the rural sentinel site compared with 3.9 mg in the urban site. This was possible because milk provided similar amounts of iron in both sites. The fortification of rice, albeit not with iron, is a step in the right direction because it is widely consumed by all social groups and in greater amounts than wheat and maize flour. Estimates from per capita household consumption for 2001 in Costa Rica are 130 g rice, 74 g wheat flour, and 18 g maize flour (26). Fortification of rice with iron is feasible but faces some barriers: high initial investment, lack of government initiative, and consumer hesitation to accept variations in appearance (27). Micronized ferric pyrophosphate may be used as the source of iron, but it has not been tried in Costa Rica yet.

The key strength of our study is that we had the data to demonstrate a plausible pathway linking the fortification program to improvements in iron status and reductions in anemia (Figure 2). These findings suggest causal effects. However, the key weakness of our study is the nature of our design, a pre/post comparison. We are unable to exclude the possibility that factors other than fortification that also changed from baseline to endline could be responsible for the decline in anemia. The 2008–2009 evaluation occurred ~6 y after full implementation of the fortification program. Efficacy studies show that responses to iron-fortified products can occur in a matter of months (4–6), but programs require longer to get established. Our findings would be more persuasive if the endline had been carried out 1–2 y after strengthening of the program was completed in 2002—namely, in 2003–2004.

We think it is unlikely that other factors caused the declines in anemia. There were modest improvements in sociodemographic factors and in nutrition in Costa Rica between 1996 and 2008 (Supplemental Table 3). For example, the percentage of the population in extreme poverty dropped from 6.9% to 3.5%. The percentage of the population with improved drinking water sources went from 94% to 96% and that with improved sanitation facilities from 90% to 94%. Expenditures on health remained similar from 1996 to 2008.

World experience with anemia is that declines occur slowly without specific nutrition interventions (1). Over the period of study, Costa Rica has had a program on iron/folate supplementation during pregnancy but no other interventions that deliver iron besides food fortification. A national survey was conducted in Costa Rica in 1982; unfortunately, the data were lost, but descriptive statistics indicate little change in anemia prevalence between 1982 and 1996. Anemia in nonpregnant women was 20.0% in 1982 (28) compared with our reported values of 18.4% for 1996 and 10.2% for 2008. These data suggest that anemia started to decline only after changes were made to the fortification program in 1999–2002. On the other hand, the prevalence of stunting (< −2 z of the WHO standards) (29), the lowest in Central America, has changed little in recent decades (30). Analyses using the WHO standards indicate that stunting was 28.9% in 1966 (30), 8.5% in 1982 (30), 7.6% in 1996 (30), and 5.6% in 2008 (31).

Our study has limitations. Ferritin was not available for women at baseline. There were no data on changes in other iron status indicators (transferrin receptor and zinc protoporphyrin), markers of inflammation (C-reactive protein and α1-acid glycoprotein), and other micronutrient indicators (zinc, vitamin A, folic acid, and vitamin B-12) to characterize fully the impact of the fortification program and to adjust for inflammation at both endpoints. We lack dietary information for women to estimate the percentage of iron requirement met. These weaknesses, but primarily our pre/post design, suggest caution in interpreting our results as causal. However, the most plausible explanation for the decline in anemia in Costa Rica is the fortification program. We believe our results support the implementation of mass fortification programs to address identified micronutrient deficiencies. Such programs should be designed to be effective, supplying sufficient iron with adequate bioavailability, and be capable of reaching the needy, including young children; this may require use of several vehicles. Our findings suggest that where micronutrient deficiencies exist and where fortification programs are designed, implemented, and monitored adequately, impact will be achieved. As many have noted (4, 7, 8), there is an urgent need for food fortification effectiveness evaluations.