Anemia affects a third of the world's population and contributes to increased morbidity and mortality, decreased work productivity, and impaired neurological development. Understanding anemia's varied and complex etiology is crucial for developing effective interventions that address the context-specific causes of anemia and for monitoring anemia control programs. We outline definitions and classifications of anemia, describe the biological mechanisms through which anemia develops, and review the variety of conditions that contribute to anemia development. We emphasize the risk factors most prevalent in low-and middle-income countries, including nutritional deficiencies, infection/inflammation, and genetic hemoglobin disorders. Recent work has furthered our understanding of anemia's complex etiology, including the proportion of anemia caused by iron deficiency (ID) and the role of inflammation and infection.Accumulating evidence indicates that the proportion of anemia due to ID differs by population group, geographical setting, infectious disease burden, and the prevalence of other anemia causes. Further research is needed to explore the role of additional nutritional deficiencies, the contribution of infectious and chronic disease, as well as the importance of genetic hemoglobin disorders in certain populations.

Prenatal lipid-based nutrient supplements can improve birth outcomes in Bangladeshi women, especially those at higher risk of fetal growth restriction. This trial was registered at clinicaltrials.gov as NCT01715038.

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Fe deficiency is a common nutritional disorder during infancy, particularly in low-income countries. The Fe status of a breast-fed infant is strongly influenced by the body Fe content at birth, which is determined by factors that operate before birth (maternal Fe status before and during pregnancy; infant gestational age and birth weight) and at the time of delivery (the timing of umbilical cord clamping). Delaying the clamping of the umbilical cord for 2 min can increase body Fe content by approximately 33% (75 mg), and results in greater Fe stores at 6 months of age. After birth, male gender and a rapid rate of weight gain are associated with lower Fe status. During the first half of infancy dietary Fe requirements depend on Fe stores at birth. For an exclusively-breast-fed full-term normal-birth-weight infant with delayed umbilical cord clamping, whose mother had adequate Fe status during pregnancy, the Fe provided from stores and breast milk is sufficient for ≥6 months, but before this time higher-risk infants may become Fe deficient. Fe supplementation can be beneficial for high-risk infants, but can have adverse effects on growth and morbidity of Fe-replete infants. After 6 months most breast-fed infants will require complementary foods that are rich in Fe.

Iron deficiency is estimated to be the most common nutritional deficiency worldwide and is particularly persistent among infants and children. The high prevalence of anemia in 6- to 9-mo-old children raises the concern that birth iron stores in some infants are inadequate to sustain growth and development through the first 6 mo of life, and postnatal factors are contributing to early depletion of iron stores and development of anemia. At the same time, there are concerns about negative effects of excess iron in infants. Maternal iron status, infant birth weight and gestational age, as well as the timing of umbilical cord clamping at birth all contribute to the establishment of adequate total body iron at birth. Postnatally, feeding practices and growth rate are factors that will affect how quickly birth iron is depleted during the first 6 mo of life. Under conditions in which maternal iron status, birth weight, gestational age, and umbilical cord clamping time are optimal, and exclusive breast-feeding is practiced, infants should have adequate iron stores for the first 6-8 mo of life. Under suboptimal conditions, infants may not reach this goal and may need to be targeted for iron supplementation before 6 mo of age.

Among fully breastfed infants with a birth weight >2500 g, IDA is uncommon before 6 mo, but male infants and those with a birth weight of 2500-2999 g are at higher risk of ID and IDA.

Table of Contents Abstract51. Introduction6 1.1 The current nutrition response to emergencies7  1.1.1 General food distributions (GFD)7  1.1.2 Supplementary feeding programs8  1.1.3 Micronutrient interventions9  1.1.4 LNS as supplements in an emergency nutrition response102. Objectives113. Methodological approach11 3.1 Dietary intake in emergency nutrition settings and composition of rations for GFD11 3.2 Hypothetical intake from example GFD rations12 3.3 Nutrient composition and adequacy of hypothetical ration13 3.4 Determination of the desired micronutrient composition of LNS16 3.5 Accounting for bioavailability of nutrients from the GFD ration and LNS20 3.6 Cost comparability estimates214. Results21 4.1 Nutrient adequacy of ‘typical’ GFD ration21  4.1.1 Hypothetical intake from and nutrient adequacy of ‘typical’ GFD ration for children 6–11 months of age21  4.1.2 Hypothetical intake from and nutrient adequacy of ‘typical’ GFD ration for children 12–35 months of age23  4.1.3 Hypothetical intake from and nutrient adequacy of ‘typical’ GFD ration for pregnant and lactating women (PLW)24 4.2 Nutrient adequacy of ‘revised’ GFD ration with the addition of LNS27  4.2.1 Age‐physiological group specific approach for developing LNS formulation30  4.2.2 ‘Age‐specific’ LNS formulation for 6–35‐month‐old infants and children30  4.2.3 Hypothetical intake from and nutrient adequacy of ‘revised’ GFD ration plus ‘age‐specific’ LNS for 6–35‐month‐old children35  4.2.4 ‘Age‐specific’ LNS formulation for PLW35  4.2.5 Hypothetical intake from and nutrient adequacy of ‘revised’ GFD ration plus ‘age‐specific’ LNS for PLW38 4.3 ‘One‐size‐fits‐all’ approach for developing LNS formulation405. Appropriate use and toxicity concerns43 5.1 Potential strategies to ensure appropriate use and to avoid inappropriate consumption506. Cost estimates of providing LNS with the ‘revised’ GFD ration527. Quality control, nutrient formulation, shelf‐life and packaging55 7.1 Quality control of LNS production56 7.2 Nutrient formulation56 7.3 Shelf‐life and packaging568. Discussion57Acknowledgements60Conflicts of interest60References60 : Planned general food distribution ration examples used for development of ‘typical’ general food distribution ration63 : Nutrient composition of principal food aid commodities used in this document65 : Protein adequacy of diets in emergency settings when supplemented with lipid‐based nutrient supplements66 List of Tables : ‘Typical’ GFD ration with CSB, and a ‘revised’ GFD ration with CSB substituted with an equivalent amount of pulse and grain12 : Energy requirements of each age/physiologic group13 : Hypothetical intake for each age/physiological group from the ‘typical’ GFD ration14 : Hypothetical intake for each age/physiological group from the ‘revised’ GFD ration, adjusted for the quantity of LNS that will be added (118 kcal)14 : Average nutrient concentrations in mature breast milk (World Health Organization 1998)15 : Adequate Intakes (AI) and Recommended Nutrient Intakes (RNIs) and Upper Levels (UL) for 7–11...

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