The iron regulation mechanisms are not exactly the same between adulthood and the early postnatal period. Also, neonatal iron status is different in full-term versus preterm infants because the prenatal/gestational period, when hepatic iron accumulates, is shortened. Newborns, especially premature infants, are at high risk of iron deficiency due to inadequate iron stores, which constitute the primary source of iron to satisfy the neonate’s increasing iron requirements. In addition, frequent blood transfusions and congenital haemochromatosis may induce iron overload in the affected neonate. To understand the cause of neonatal iron deficiency/overload and to promote the development of effective therapeutic interventions in humans, different animal models have been generated by genetic engineering, low-/high-iron diets, phlebotomy/transfusion and surgical manipulation. These models use various laboratory and domestic animals to study iron imbalance. They serve as surrogate models for experiments that are ethically or practically unfeasible to conduct on human neonates. Although an animal model for studying neonatal iron disorders may not fully replicate the complexities of human diseases, it is designed to model specific aspects of these conditions. Combined data from multiple models can help to offset the limitations inherent in each individual model. In this review, we outline approaches to induce neonatal iron disorders, current animal models of full-term and preterm neonates, and recommendations for diagnosis.

Bioarchaeologists commonly record porous cranial lesions (PCLs). They have varied etiologies but are frequently associated with nutritional anemia without a differential diagnosis. This article provides a literature review, evaluates diet in the US Southwest over time, and identifies issues with associating PCLs with poor diet in this region. Generally, diet was adequate across time and space. Although maize was a dietary staple, other food items such as rabbits and amaranth provided complementary micronutrients. PCLs exhibit varied morphologies, which generally correspond with age: those characterized by fine, scattered porosity are associated with younger ages at death. Variation in PCL morphology indicates different and sometimes unrelated etiologies. Nutritional anemia is an insufficient explanation for PCL frequency in the Southwest, partly because the diet was adequate across time.

Protein-losing enteropathy is a severe complication of Fontan surgery and is associated with anaemia. Few studies have reported on the efficacy of an intravenous iron infusion for treating protein-losing enteropathy and low albuminemia after Fontan surgery. Herein, we present two cases of female patients who suffered from protein-losing enteropathy and low albuminemia following Fontan surgery, both of whom improved after an intravenous iron infusion.

Iron is essential for many physiological functions of the body, and it is required for normal growth and development. Iron deficiency (ID) is the most common form of micronutrient malnutrition and is particularly prevalent in infants and young children in developing countries. Iron supplementation is considered the most effective strategy to combat the risk of ID and ID anaemia (IDA) in infants, although iron supplements cause a range of deleterious gut-related problems in malnourished children. The purpose of this review is to assess the available evidence on the effect of iron supplementation on the gut microbiota during childhood ID and to further assess whether prebiotics offer any benefits for iron supplementation. Prebiotics are well known to improve gut-microbial health in children, and recent reports indicate that prebiotics can mitigate the adverse gut-related effects of iron supplementation in children with ID and IDA. Thus, provision of prebiotics alongside iron supplements has the potential for an enhanced strategy for combatting ID and IDA among children in the developing world. However, further understanding is required before the benefit of such combined treatments of ID in nutritionally deprived children across populations can be fully confirmed. Such enhanced understanding is of high relevance in resource-poor countries where ID, poor sanitation and hygiene, alongside inadequate access to good drinking water and poor health systems, are serious public health concerns.

Adolescent girls are an important target group for micronutrient interventions particularly in Sub-Saharan Africa where adolescent pregnancy and micronutrient deficiencies are common. When consumed in sufficient amounts and at levels appropriate for the population, fortified foods may be a useful strategy for this group, but little is known about their effectiveness and timing (regarding menarche), particularly in resource-poor environments. We evaluated the effect of consuming multiple micronutrient-fortified biscuits (MMB), sold in the Ghanaian market, 5 d/week for 26 weeks compared with unfortified biscuits (UB) on the micronutrient status of female adolescents. We also explored to what extent the intervention effect varied before or after menarche. Ten2Twenty-Ghana was a 26-week double-blind, randomised controlled trial among adolescent girls aged 10–17 years (n 621) in the Mion District, Ghana. Biomarkers of micronutrient status included concentrations of Hb, plasma ferritin (PF), soluble transferrin receptor (TfR) and retinol-binding protein (RBP), including body-iron stores. Intention-to-treat analysis was supplemented by protocol-specific analysis. We found no effect of the intervention on PF, TfR and RBP. MMB consumption did not affect anaemia and micronutrient deficiencies at the population level. MMB consumption increased the prevalence of vitamin A deficiency by 6·2 % (95 % CI (0·7, 11·6)) among pre-menarche girls when adjusted for baseline micronutrient status, age and height-for-age Z-score, but it decreased the prevalence of deficient/low vitamin A status by −9·6 % (95 % CI (−18·9, −0·3)) among post-menarche girls. Consuming MMB available in the market did not increase iron status in our study, but reduced the prevalence of deficient/low vitamin A status in post-menarcheal girls.

Anaemia is characterised by low hemoglobin (Hb) concentration. Despite being a public health concern in Ethiopia, the role of micronutrients and non-nutritional factors as a determinant of Hb concentrations has been inadequately explored. This study focused on the assessment of serum micronutrient and Hb concentrations and a range of non-nutritional factors, to evaluate their associations with the risk of anaemia among the Ethiopian population (n 2046). It also explored the mediation effect of Zn on the relation between se and Hb. Bivariate and multivariate regression analyses were performed to identify the relationship between serum micronutrients concentration, inflammation biomarkers, nutritional status, presence of parasitic infection and socio-demographic factors with Hb concentration (n 2046). Sobel–Goodman test was applied to investigate the mediation of Zn on relations between serum se and Hb. In total, 18·6 % of participants were anaemic, 5·8 % had iron deficiency (ID), 2·6 % had ID anaemia and 0·6 % had tissue ID. Younger age, household head illiteracy and low serum concentrations of ferritin, Co, Cu and folate were associated with anaemia. Serum se had an indirect effect that was mediated by Zn, with a significant effect of se on Zn (P < 0·001) and Zn on Hb (P < 0·001). The findings of this study suggest the need for designing a multi-sectorial intervention to address anaemia based on demographic group.

The iron-regulatory hormone hepcidin is transcriptionally up-regulated by gluconeogenic signals. Recent evidence suggeststhat increases in circulating hepcidin may decrease dietary iron absorption following prolonged exercise, however evidence is limited on whether gluconeogenic signals contribute to post-exercise increases in hepcidin. Mice with genetic knockout of regulated in development and DNA response-1 (REDD1) display greater glycogen depletion following exercise, possibly indicating greater gluconeogenesis. The objective of the present study was to determine liver hepcidin, markers of gluconeogenesis and iron metabolism in REDD1 knockout and wild-type mice following prolonged exercise. Twelve-week-old male REDD1 knockout and wild-type mice were randomised to rest or 60 min treadmill running with 1, 3 or 6 h recovery (n = 5–8/genotype/group). Liver gene expression of hepcidin (Hamp) and gluconeogenic enzymes (Ppargc1a, Creb3l3, Pck1, Pygl) were determined by qRT-PCR. Effects of genotype, exercise and their interaction were assessed by two-way ANOVAs with Tukey's post-hoc tests, and Pearson correlations were used to assess the relationships between Hamp and study outcomes. Liver Hamp increased 1- and 4-fold at 3 and 6 h post-exercise, compared to rest (P-adjusted < 0⋅009 for all), and was 50% greater in REDD1 knockout compared to wild-type mice (P = 0⋅0015). Liver Ppargc1a, Creb3l3 and Pck1 increased with treadmill running (P < 0⋅0001 for all), and liver Ppargc1a, Pck1 and Pygl were greater with REDD1 deletion (P < 0⋅02 for all). Liver Hamp was positively correlated with liver Creb3l3 (R = 0⋅62, P < 0⋅0001) and Pck1 (R = 0⋅44, P = 0⋅0014). In conclusion, REDD1 deletion and prolonged treadmill running increased liver Hamp and gluconeogenic regulators of Hamp, suggesting gluconeogenic signalling of hepcidin with prolonged exercise.

Excess unabsorbed iron in the gastrointestinal tract may select for enteric pathogens and increase the incidence and severity of infectious disease. Aspergillus oryzae (Ao) is a filamentous fungus that has the ability to accumulate and store large amounts of iron, and when used as a supplement or fortificant, has similar absorption to ferrous sulphate (FeSO4) in humans. The objective of this study was to determine the effect of iron-enriched Ao (Ao iron) compared with FeSO4 on iron accumulation, growth and motility of the Gram-negative enteric pathogen, S. Typhimurium. S. Typhimurium was cultured in media containing no added iron or 1 μM elemental iron as either Ao iron or FeSO4. S. Typhimurium cultured with FeSO4 accumulated more iron than those cultured with Ao iron. Genes regulated by the iron-activated transcriptional repressor, Fur, did not differ between control and Ao iron, but decreased in S. Typhimurium cultured with FeSO4 compared with both groups. Growth of S. Typhimurium was greater when cultured with FeSO4 compared with Ao iron and control. S. Typhimurium swam faster, had greater acceleration and travelled further when cultured with FeSO4 compared with Ao iron and control; swim speed, acceleration and distance travelled did not differ between Ao iron and control. These findings provide evidence that Ao iron reduces the virulence of a common enteric pathogen in vitro. Further research is required to determine whether iron-enriched Ao is a suitable iron supplement to improve iron delivery in areas with a high infection burden.

Anaemia in pregnancy is a persistent health problem in Nepal and could be reduced through nutrition counselling and strengthened iron folic acid supplementation programmes. We analysed 24-hour diet recall data from 846 pregnant women in rural plains Nepal, using linear programming to identify the potential for optimised food-based strategies to increase iron adequacy. We then conducted qualitative research to analyse how anaemia was defined and recognised, how families used food-based strategies to address anaemia, and the acceptability of optimised food-based strategies. We did 16 interviews of recently pregnant mothers, three focus group discussions with fathers, three focus group discussions with mothers-in-law and four interviews with key informants. Dietary analyses showed optimised diets did not achieve 100 % of recommended iron intakes, but iron intakes could be doubled by increasing intakes of green leaves, egg and meat. Families sought to address anaemia through food-based strategies but were often unable to because of the perceived expense of providing an ‘energy-giving’ diet. Some foods were avoided because of religious or cultural taboos, or because they were low status and could evoke social consequences if eaten. There is a need for counselling to offer affordable ways for families to optimise iron adequacy. The participation of communities in tailoring advice to ensure cultural relevance and alignment with local norms is necessary to enable its effectiveness.

Worldwide, there are limited data on the prevalence of postpartum anaemia and iron status. The aims of the present study were to assess the prevalence of anaemia and iron deficiency (ID) by three iron indicators 14 weeks postpartum, their relations to haemoglobin (Hb) and associations with ethnicity and clinical factors in a multi-ethnic population. We conducted a population-based cohort study of 573 women followed from early pregnancy. The prevalence of postpartum anaemia (Hb <12·0 g/dl) was 25 %. ID prevalence varied from 39 % by serum ferritin (SF <15 μg/l), to 19 % by soluble transferrin receptor (sTfR >4·4 mg/l) and 22 % by total body iron (TBI < 0 mg/kg). The mean Hb concentration was 12·8 g/dl in women with no ID, 12·6 g/dl in those with ID by SF only and 11·6 g/dl in those with ID by SF, sTfR and TBI. ID by sTfR and TBI defined by the current threshold values probably identified a more severe iron-deficient population compared with ID assessed by SF. Compared with Western Europeans, the prevalence of anaemia was at least the double in ethnic minorities (26–40 % v. 14 %; P < 0·01–0·05), and the prevalence of ID by sTfR and TBI, but not of ID by SF < 15 μg/l, was significantly higher in some minority groups. After adjustment for covariates, only South Asians had lower Hb and higher sTfR concentration. Insufficient iron intake, gestational anaemia or ID, and postpartum haemorrhage were associated with lower postpartum Hb concentration and poorer iron status.

Exposure to early-life adversity (ELA) and iron deficiency early in life are known risk factors for suboptimal brain and socioemotional development. Iron deficiency may arise from and co-occur with ELA, which could negatively affect development. In the present study, we investigated whether ELA is associated with iron deficiency in infants receiving no iron supplementation. This study is a secondary analysis of extant data collected in the 1990s; participants were healthy infants from working-class communities in Santiago, Chile (N = 534, 45.5% female). We measured stressful life events, maternal depression, and low home support for child development during infancy and assessed iron status when the infant was 12 months old. Slightly more than half of the infants were iron-deficient (51%), and 25.8% were iron-deficient anemic at 12 months. Results indicated that ELA was associated with lower iron levels and iron deficiency at 12 months. The findings are consistent with animal and human prenatal models of stress and iron status and provide evidence of the association between postnatal ELA and iron status in humans. The findings also highlight a nutritional pathway by which ELA may impact development and present a nutritionally-focused avenue for future research on ELA and psychopathology.

Childhood malnutrition is known as a public health concern globally. The present study aims to assess the anthropometry and blood biochemical status of rural primary schoolchildren in Malaysia. A total of 776 children (7–11 years old) from ten rural primary schools from five states were included in this study. Nutritional outcomes were assessed based on sex, age group and school categories among the children (median age: 9 years (P25:8, P75:10)). The overall prevalence of malnutrition was 53·4 %. Vitamin A deficiency (VAD) was recorded at 20·6 and 39·8 % based on retinol and retinol-binding protein (RBP) levels, respectively. Anaemia, iron deficiency (ID), iron-deficiency anaemia (IDA) and elevated inflammation were found at 14·9, 17·9, 9·1 and 11·5 %, respectively. Malnutrition, VAD, anaemia, ID, IDA and elevated inflammation were more prevalent among Orang Asli (OA) schoolchildren compared with Non-Orang Asli schoolchildren. Higher occurrences of VAD and anaemia were also found among children aged <10 years. Retinol, RBP, α-carotene, ferritin and haemoglobin levels were lower among undernourished children. Besides, overweight/obese children exhibited a higher level of high-sensitivity C-reactive protein. Multivariate analysis demonstrated that OA school children (adjusted OR (AOR): 6·1; 95 % CI 4·1, 9·0) and IDA (AOR: 3·6; 95 % CI 1·9, 6·6) were associated with stunting among this population. The present study revealed that malnutrition, micronutrient deficiencies and anaemia are prevalent among rural primary schoolchildren in Malaysia, especially those from OA schools and younger age children (<10 years). Hence, more appropriate and targeted measures are needed to improve the nutritional status of these children.

In 2013, the Danish Health Authorities recommended a change in prophylactic iron supplementation to 40–50 mg/d from gestational week 10. Hence, the aims of the present study were (1) to estimate the prevalence of women who follow the Danish recommendation on iron supplementation during the last 3 weeks of the first trimester of pregnancy and (2) to identify potential sociodemographic, reproductive and health-related pre-pregnancy predictors for iron supplementation during the first trimester. We conducted a cross-sectional study with data from the hospital-based Copenhagen Pregnancy Cohort. Characteristics were analysed by descriptive statistics and multivariable logistic regression analysis was performed to examine the associations between predictors and iron supplementation during the last 3 weeks of the first trimester. The study population consisted of 23 533 pregnant women attending antenatal care at Copenhagen University Hospital - Rigshospitalet from October 2013 to May 2019. The prevalence of iron supplementation according to recommendations was 49⋅1 %. The pre-pregnancy factors of ≥40 years of age, the educational level below a higher degree and a vegetarian or vegan diet were identified as predictors for iron supplementation during the first trimester of pregnancy. Approximately half of the women were supplemented with the recommended dose of iron during the first trimester of pregnancy. We identified pre-pregnancy predictors associated with iron supplementation. Interventions that target women of reproductive age are needed. An enhanced focus on iron supplementation during pregnancy should be incorporated in pre-pregnancy and interpregnancy counselling.

India is coming to grips with a stage of nutrition transition. According to the Food Safety and Standards Authority of India (FSSAI), preventable micronutrient deficiency is arising public health precedence in India. However, the foremost public health concern is the lack of national prevalence data. The present study was carried out to estimate the pooled age-wise prevalence of six preventable micronutrient deficiencies (vitamin A, vitamin B12, vitamin D, iron, iodine and folic acid) in India. A systematic review was carried out on PubMed and Global Index Medicus databases using the Boolean search strategy. Statistical analyses were done using R software, version 3.6. 2. PRISMA guidelines were strictly adhered to during the review. A preliminary literature search yielded 4302 articles; however, 270 original research articles were found eligible to be included in quantitative synthesis. The estimated overall prevalence was 17 % [95 % confidence interval (CI) 0⋅07, 0⋅26] for iodine deficiency, 37 % (95 % CI 0⋅27, 0⋅46) for folic acid deficiency, 54 % (95 % CI 0⋅49, 0⋅59) for iron deficiency, 53 % (95 % CI 0⋅41, 0⋅64) for vitamin B12 deficiency, 19 % (95 % CI 0⋅09, 0⋅29) for vitamin A deficiency and 61 % (95 % CI 0⋅07, 0⋅26) for vitamin D with high heterogeneity. We classified the population into infants (0–5 years), adolescents (<18 years), adults (>18 years) and pregnant women. Iron deficiency was most prevalent (61 %) in pregnant women. The results of the present study reinforce the data on micronutrient deficiency in India and warrant the immediate need for further active public health interventions to address these deficiencies. The study is registered with PROSPERO (CRD42020205043).