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PUBLIC HEALTH

# Anemia in women — an intractable problem that requires innovative solutions

### Subjects

A new spatial analysis calls for a tiered and geographically targeted approach to tackling the vast, ongoing burden of anemia in women within low- and middle-income countries.

Anemia in women of reproductive age (15–49 years of age) in low- and middle-income countries (LMICs) continues to be an intractable problem of ‘hidden hunger’, exemplifying gender health inequities and a shameful loss of human capital. The low hemoglobin concentration in blood that defines anemia occurs long after tissue iron stores have been depleted to levels associated with suboptimal function. A major cause of anemia, this iron deficiency leads to diminished oxygen-carrying capacity in red blood cells, which in turn diminishes energy efficiency, work capacity and productivity1. In addition, severe anemia in pregnancy is consistently linked to maternal mortality2. Anemia in women of reproductive age is concentrated in LMICs and requires urgent and immediate attention. In this issue of Nature Medicine, Kinyoki and colleagues set out to model the prevalence and burden of mild, moderate and severe anemia in LMICs over the past two decades3.

The study examines data from several databases across 82 LMICs, comprising 218 geo-referenced household surveys conducted between 2000 and 2018 and including over three million women. On the basis of their analysis, the authors estimate half a billion women were living with anemia in LMICs in 2018. In the period from 2000 to 2018, they find limited decreases in anemia prevalence (35.6% to 31.6%) and an increase in years lived with disability, due to population growth. They reveal widespread sub-national disparities and predict that a vast majority of countries will fail to achieve the World Health Organization global nutrition target of a 50% reduction in anemia prevalence by 2030. Although limited by data quality and quantity gaps, this novel analysis provides an opportunity to shed light, anew, on an important public-health problem and public-policy failure.

Physical productivity losses due to iron deficiency have been linked to the gross domestic product and potentially result in losses of billions of dollars annually4 (although more-robust and more-comprehensive estimates are needed). A recent analysis estimated gains of 2.28 million school years and US$8.25 billion in lifetime income associated with scaling-up of antenatal iron–folic acid supplementation5. An economic and human capital case is therefore well justified to convey the urgent need for programmatic action to policymakers and economic planners. India, with its high prevalence rate of 50%, has the largest number of women of reproductive age with anemia (181.3 million) and harbors two thirds of the LMICs' cases3; clearly, it could accrue an enormous economic benefit by addressing this problem. Another 87 million women with anemia live in China, Pakistan and Nigeria. Tackling this massive problem has been challenging because of issues such as gender inequality, failure of programs and reliance on economic development (and dietary change), which all stem in part from a general lack of political will. Etiologies such as malaria, soil-transmitted helminths and chronic inflammation do exist and may explain some of the geographic heterogeneity; however, iron deficiency and other nutritional causes of anemia predominate in women3 and may be linked to gender inequality in terms of access to a high-quality diet and, specifically, food sources rich in iron6. Highly bioavailable heme sources (meat, eggs and liver) are needed to meet the daily requirements for iron, which in women are set at 18 mg. One portion of three ounces (85 grams) of red meat provides 2.6 mg of iron, one medium egg provides 0.6 mg of iron, and a poorly absorbed plant source such as a cup (30 grams) of spinach provides only 0.8 mg of iron. Consuming all three daily portions will meet only 22% of the recommended daily allowance for iron; the quality of diets for women in LMICs is much worse than this, and requirements are higher during pregnancy. Also, the recommended levels of intake would be insufficient to correct deficiency, particularly in a context in which 40–50% of the population is anemic. Linear programming has demonstrated that food-based strategies alone may not be sufficient to meet the dietary needs of women, calling for fortification and supplementation approaches instead7. Antenatal iron–folic acid supplementation is an evidence-based, highly affordable (US$1 per pregnancy) and recommended intervention. Nevertheless, large-scale programs have failed to achieve adequate coverage because of supply-chain breakdowns and low adherence. Political will and global momentum for maternal nutrition is lacking, with limited spending on maternal versus child health interventions8. Also, there is reliance on income growth for addressing the widely accepted drivers of change in anemia prevalence, such as female education, dietary improvement, and water, sanitation and hygiene9. However, anemia rates decrease only a quarter as fast as income increases10. Moreover, there is lack of data showing that behavior-change approaches for dietary diversification work, and there is evidence that interventions in water, sanitation and hygiene do not affect anemia11 (although both seem appropriate to do in the long run, and for their own sake). The slow decrease in anemia prevalence in women3 therefore calls for a different approach and a substantial commitment.

The analysis by Kinyoki et al.3 may help guide the future course of action. The type of resolute data generated, if used to create mapping and tracking tools, could be a powerful means for geographic targeting, resource allocation, deploying interventions and monitoring progress. In addition, a tiered, life-course approach (Fig. 1) may help to combat this problem. For the general population, a robust food-fortification effort is needed and has been proven to be effective for diminishing anemia in women of reproductive age12. Where the prevalence of anemia is high, fortification can be augmented with intermittent (weekly) iron supplementation as recommended by the World Health Organization. During pregnancy, supplementation with iron plus folic acid or, better still, with multiple micronutrients needs to be boosted through antenatal care and other platforms, alongside context-specific use of deworming and intermittent preventive treatment of malaria during pregnancy. Antenatal hemoglobin screening, which is recommended but poorly implemented, can be used in the context of treating the more severe forms of anemia with short-infusion, intravenously administered iron, as is practiced in high-income countries. If each tier in this strategy is effective, then the next tier will be smaller, as prevention is the goal.

There is an urgent need for more-accurate field-based diagnostics and point-of-care systems than the hemoglobinometers now used provide. Non-invasive technologies, including pulse oximetry, show some promise and greater acceptability, but their diagnostic performance needs improvement. Point-of-care systems for identifying underlying causes (iron deficiency, inflammation and hemoglobinopathy) are also needed as the field moves toward more-precise public-health prevention and treatment strategies. Much-needed work on redefining hemoglobin cut-offs for anemia seems to be underway, and treatment protocols also require updating. Treatment regimens with intravenous administration of low-molecular-weight iron products such as ferric carboxy maltose and ferric derisomaltose are promising but will require an affordable ‘price point’ for the LMIC context. The COVID-19 pandemic has exacerbated food and nutrition insecurity in LMICs and has done so disproportionately for women and children. Maternal anemia is a scourge that cannot exist in such proportions and calls for immediate, large-scale equity-based and economically justified action.

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Correspondence to Parul Christian.

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The author declares no competing interests.

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Christian, P. Anemia in women — an intractable problem that requires innovative solutions. Nat Med 27, 1675–1677 (2021). https://doi.org/10.1038/s41591-021-01514-3