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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.

The optimal timing of umbilical cord clamping has been debated in the scientific literature for at least the last century, when cord clamping practices shifted from delayed towards immediate clamping. Recent research provides evidence for the beneficial effect of delayed cord clamping on infant iron status. The present review describes the physiological basis for the impact of cord clamping time on total body iron at birth and the relationship between birth body iron, as affected by cord clamping time, and iron status later in infancy. This research is discussed in the context of current clamping practices, which tend towards early cord clamping in most settings, as well as the high levels of anemia present in young infants in many countries worldwide.

To understand the factors contributing to changes in breastfeeding duration, we analyzed data from seven countries in Latin America and from Haiti to document changes in breastfeeding duration between 1986 and 2005. We used a novel method that permits the overall change to be separated into the portion attributable to changing population characteristics (e.g., greater urban population or increased maternal employment) and the portion resulting from changing breastfeeding behaviors within population subgroups (e.g., more breastfeeding among urban women). Our results indicate that in the low-to-middle-income countries studied, which are experiencing socioeconomic and demographic changes, improvements in breastfeeding duration occurred. These improvements are explained almost entirely by changing breastfeeding behaviors, which were particularly evident in certain subgroups of women, such as those with higher levels of education, and very little by changing population characteristics. The socioeconomic and demographic changes we studied that were previously associated with less breastfeeding no longer appear to have a large negative effect. Our findings show that individual behaviors are amenable to change and that changes in individual behaviors collectively contribute to positive national trends in breastfeeding.

[Image: see text] [Table: see text] [Table: see text] [Table: see text] [Table: see text] ABSTRACT: The term ‘lipid‐based nutrient supplements’ (LNS) refers generically to a range of fortified, lipid‐based products, including products like Ready‐to‐Use Therapeutic Foods (RUTF) (a large daily ration with relatively low micronutrient concentration) as well as highly concentrated supplements (1–4 teaspoons/day, providing

Delayed clamping of the umbilical cord increases the infant's iron endowment at birth and haemoglobin concentration at 2 months of age. We aimed to assess whether a 2-minute delay in the clamping of the umbilical cord of normal-weight, full-term infants improved iron and haematological status up to 6 months of age.476 mother-infant pairs were recruited at a large obstetrics hospital in Mexico City, Mexico, randomly assigned to delayed clamping (2 min after delivery of the infant's shoulders) or early clamping (around 10 s after delivery), and followed up until 6 months postpartum. Primary outcomes were infant haematological status and iron status at 6 months of age, and analysis was by intention-to-treat. This study is registered with ClinicalTrials.gov, number NCT00298051.358 (75%) mother-infant pairs completed the trial. At 6 months of age, infants who had delayed clamping had significantly higher mean corpuscular volume (81.0 fL vs 79.5 fL 95% CI -2.5 to -0.6, p=0.001), ferritin (50.7 mug/L vs 34.4 mug/L 95% CI -30.7 to -1.9, p=0.0002), and total body iron. The effect of delayed clamping was significantly greater for infants born to mothers with low ferritin at delivery, breastfed infants not receiving iron-fortified milk or formula, and infants born with birthweight between 2500 g and 3000 g. A cord clamping delay of 2 minutes increased 6-month iron stores by about 27-47 mg.Delay in cord clamping of 2 minutes could help prevent iron deficiency from developing before 6 months of age, when iron-fortified complementary foods could be introduced.

Maternal undernutrition and newborn stunting (birth length-for-age z-score < -2) are common in Bangladesh. In the Rang-Din Nutrition Study, a cluster-randomized effectiveness trial underway in northwest Bangladesh, pregnant women received either a) iron & folic acid (IFA) or b) lipid-based nutrient supplement (LNS, 20 g/d, 118 kcal) designed to enrich local diets of pregnant women with essential fatty acids, high-quality protein and 22 micronutrients. Women (n=4011) were enrolled at 13.1 ± 3.4 wk gestation; 40% were nulliparous and 31% were underweight (BMI < 18.5 kg/m2). In the full sample, there were significant reductions in newborn stunting [18.6 vs. 22.5%, adjusted relative risk (ARR)=0.83 (0.70, 0.96)] and small head circumference (HC z-score < -2) [20.8 vs. 24.7%, ARR=0.82 (0.71, 0.95)] in the LNS vs. IFA group; the difference in low birth weight was marginally significant (36.8 vs. 39.1%, p=0.087). LNS distribution was interrupted for 10 wk in 2012; among women who gave birth before the interrupti...

Iron deficiency (ID) can occur among exclusively breastfed infants before 6 mo of age.The objective was to determine which subgroups of fully breastfed infants are at highest risk of ID.We assessed the prevalence of ID (ferritin12 mug/L) and iron deficiency anemia (IDA; ferritin12 mug/L and hemoglobin105 g/L) and risk factors associated with ID and IDA at 6 mo among 404 fully breastfed infants with a birth weight2500 g from 6 studies in Ghana, Honduras, Mexico, and Sweden. Infants with an elevated C-reactive protein concentration (8%) were excluded.The percentages of infants with ID were 6% in Sweden, 17% in Mexico, 13-25% in Honduras, and 12-37% in Ghana. The percentages with IDA were 2% in Sweden, 4% in Mexico, 5-11% in Honduras, and 8-16% in Ghana. With data pooled, the key predictors of ID (20%) were male sex [adjusted odds ratio (AOR): 4.6; 95% CI: 2.5, 8.5] and birth weight 2500-2999 g (AOR: 2.4; 95% CI: 1.4, 4.3). The predictors of IDA (8%) were male sex (AOR: 7.6; 95% CI: 2.5, 23.0), birth weight of 2500-2999 g (AOR: 3.4; 1.5, 7.5), and weight gain above the median since birth (AOR: 3.4; 95% CI: 1.3, 8.6). The combination of birth weight 2500-2999 g or male sex had a sensitivity of 91% for identifying ID and of 97% for identifying IDA.Among fully breastfed infants with a birth weight2500 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.

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.

Efforts to develop global programs for the control of iron deficiency require simple, low-cost, and accurate indicators of iron status.We aimed to compare estimates of body iron (BI) stores, as calculated from either plasma ferritin concentration alone (BI-ferritin) or the ratio of plasma transferrin receptor (TfR) to ferritin (BI-TfR/ferritin).Data were analyzed from 4 previously completed, randomized intervention trials that enrolled infants, schoolchildren, or pregnant women (total n = 1189, after excluding subjects with elevated C-reactive protein).The correlation coefficients between BI-ferritin and BI-TfR/ferritin were0.95 for all studies. The kappa index ranged from 0.5 to 1.0. All of the sensitivities of BI-ferritin for identifying persons with low iron stores (defined as BI-TfR/ferritin0 mg/kg body wt) were0.90. All of the specificities were0.90 except the study of pregnant women (specificity = 0.66). The effect sizes of iron intervention trials were significantly greater for change in iron reserves estimated by BI-TfR/ferritin than by BI-ferritin in 2 studies with larger effect sizes (1.11 compared with 1.00 and 1.56 compared with 1.44, respectively; P0.05) and 1 study with medium effect size (0.70 compared with 0.57; P0.05). However, there were no significant differences between estimates of these effect sizes for 1 study with a medium effect size and 1 study with a smaller effect size (0.78 compared with 0.83 and 0.37 compared with 0.35, respectively; P0.2).Plasma ferritin concentration alone provides a good approximation of total BI reserves, as estimated by BI-TfR/ferritin, on the basis of high correlation, sensitivity, and specificity among nonpregnant persons with unelevated C-reactive protein.

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.