Association Between Hemoglobin Levels and Efficacy of Intravenous Ferric Carboxymaltose in Patients With Acute Heart Failure and Iron Deficiency: An AFFIRM-AHF Subgroup Analysis.

BACKGROUND: Iron deficiency, with or without anemia, is an adverse prognostic factor in heart failure (HF). In AFFIRM-AHF (a randomized, double-blind placebo-controlled trial comparing the effect of intravenous ferric carboxymaltose on hospitalizations and mortality in iron-deficient subjects admitted for acute heart failure), intravenous ferric carboxymaltose (FCM), although having no significant effect on the primary end point, reduced the risk of HF hospitalization (hHF) and improved quality of life versus placebo in iron-deficient patients stabilized after an acute HF (AHF) episode. These prespecified AFFIRM-AHF subanalyses explored the association between hemoglobin levels and FCM treatment effects. METHODS: AFFIRM-AHF was a multicenter, double-blind, randomized, placebo-controlled trial of FCM in hospitalized AHF patients with iron deficiency. Patients were stratified by baseline hemoglobin level (<12 versus ≥12 g/dL). In each subgroup, the primary composite (total hHF and cardiovascular death) and secondary (total hHF; total cardiovascular hospitalizations and cardiovascular death; time to cardiovascular death, and time to first/days lost due to hHF or cardiovascular death) outcomes were assessed with FCM versus placebo at week 52. Sensitivity analyses using the World Health Organization anemia definition (hemoglobin level <12 g/dL [women] or <13 g/dL [men]) were performed, among others. RESULTS: Of 1108 AFFIRM-AHF patients, 1107 were included in these subanalyses: 464 (FCM group, 228; placebo group, 236) had a hemoglobin level <12 g/dL, and 643 (FCM, 329; placebo, 314) had a hemoglobin level ≥12 g/dL. Patients with a hemoglobin level <12 g/dL were older (mean, 73.7 versus 69.1 years), with more frequent previous HF (75.0% versus 68.7%), serum ferritin <100 µg/L (75.4% versus 68.1%), and transferrin saturation <20% (87.9% versus 81.4%). For the primary outcome, annualized event rates per 100 patient-years with FCM versus placebo were 71.1 and 73.6 (rate ratio, 0.97 [95% CI, 0.66-1.41]), respectively, and 48.5 versus 72.9 (RR, 0.67 [95% CI, 0.48-0.93]) in the hemoglobin levels <12 and ≥12 g/dL subgroups, respectively. No significant interactions between hemoglobin subgroup and treatment effect were observed for primary (Pinteraction=0.15) or secondary outcomes. Changes from baseline in hemoglobin, serum ferritin and transferrin saturation were significantly greater with FCM versus placebo in both subgroups between weeks 6 and 52. Findings were similar using the World Health Organization definition for anemia. CONCLUSIONS: The effects of intravenous FCM on outcomes in iron-deficient patients stabilized after an AHF episode, including improvements in iron parameters over time, did not differ between patients with hemoglobin levels <12 and ≥12 g/dL. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02937454.

Micronutrient deficiency and supplements in schoolchildren and teenagers.

PURPOSE OF REVIEW: The essential micronutrients are corner stones in the functional and physical development. Early deficiency has life-long consequences. While awareness about iron deficiency is relatively high, it remains lower for other micronutrients. This review aims at reporting on recent data and attracting attention to the high prevalence of micronutrient deficiencies in school-age and adolescent individuals. RECENT FINDINGS: Iron deficiency anaemia remains highly prevalent worldwide and the most frequent deficiency but can be corrected with simple tools ranging from food fortification, nutritional intervention, and to supplements. The link between micronutrient (MN) deficiency and neurobehavioral disorders is increasingly established and is worrying even in Western countries. Paediatric individuals are prone to imbalanced diets and picky eating behaviour, and their diets may then become incomplete: the highest risk for deficiency is observed for iron, zinc and vitamin D. SUMMARY: There is not much new information, but rather confirmation of the importance of health policies. Well conducted randomized controlled trials confirm that deficiencies can be corrected efficiently including with food fortification, and result in clinical benefits. Individual complementation should be considered in children and adolescents with proven deficiency.

Early iron supplementation in exclusively breastfed Gambian infants: a randomized controlled trial.

Objective: To investigate the effect of daily iron supplementation for 14 weeks on the serum iron concentration and other markers of iron status in exclusively breastfed infants in Gambia. Methods: A placebo-controlled, randomized, double-blind trial was performed in rural Gambia between 3 August 2021 and 9 March 2022. Overall, 101 healthy, exclusively breastfed infants aged 6 to 10 weeks were recruited at vaccination clinics and through community health workers. Infants were randomized to receive iron supplementation (7.5 mg/day as ferrous sulfate in sorbitol solution) or placebo for 98 days. Venous blood samples were collected at baseline and on day 99 to assess the serum iron concentration and other markers of iron and haematological status. Findings: At day 99, the serum iron concentration was significantly higher in the iron supplementation group than the placebo group (crude difference in means: 2.5 µmol/L; 95% confidence interval: 0.6 to 4.3) and there were significant improvements in other iron and haematological markers. There were 10 serious adverse events (five in each group), 106 non-serious adverse events (54 with iron supplementation; 52 with placebo) and no deaths. There was no marked difference between the groups in maternally reported episodes of diarrhoea, fever, cough, skin infection, eye infection or nasal discharge. Conclusion: In exclusively breastfed Gambian infants, iron supplementation from 6 weeks of age was associated with a significant improvement in markers of iron status at around 6 months of age. There was no indication of adverse effects on growth or infections.

Ten2Twenty-Ghana: a randomised controlled trial on the efficacy of multiple micronutrient-fortified biscuits on the micronutrient status of adolescent girls.

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.

The promotion mechanism of different nitrogen doping types on the catalytic activity of activated carbon electro-Fenton cathode: Simultaneous promotion of H2O2 generation and phenol degradation ability.

Doping with nitrogen atoms can improve the catalytic activity of activated carbon cathodes in electro-Fenton systems, but currently there is a lack of understanding of the catalytic mechanism, which limits the further development of high-performance activated carbon cathodes. Here, a multi-scale exploration was conducted using density functional theory and experimental methods to investigate the mechanism of different nitrogen doping types promoting the redox performance of activated carbon cathodes and the degradation of phenol. The density functional theory results indicate that the introduction of nitrogen atoms enhances the binding ability between carbon substrates and oxygen-containing substances, promotes the localization of surrounding electrons, and makes it easier for O2 to bind with protons and catalyze the hydrogenation reaction of *OOH. Due to its weak binding ability with oxygen-containing substances, AC is difficult to form H2O2, resulting in a tendency towards the 4e-ORR pathway. The binding energy between graphite-N carbon substrate and pyridine-N carbon substrate with *OOH is closer to the volcano top, so graphite n and pyridine n can better promote the selectivity of activated carbon for 2e-ORR. In addition, the calculation results also indicate that pyrrole-N and graphite-N are more capable of catalyzing the reaction energy barrier between ·OH and phenol. Finally, the simulation results were used to guide the modification of nitrogen doped activated carbon and experimental verification was carried out. The degradation results of phenol confirmed the efficient synergistic effect between different types of nitrogen doping, and the NAC-800 electrode exhibited efficient and stable characteristics. This work provides a guiding strategy for further developing stable and highly selective activated carbon cathode materials.

Habitual intake of iron, copper, and zinc and the risk of type 2 diabetes in a prospective cohort: The CAVAS (Cardiovascular Disease Association Study).

BACKGROUND AND AIMS: Unlike iron, evidence of the association between dietary copper and zinc intake and type 2 diabetes (T2D) risk is limited. This study aimed to examine the prospective associations of dietary intake of iron (total, plant-based, and animal-based), copper, and zinc with T2D risk among adults aged ≥40 years. METHODS AND RESULTS: For 16,666 participants, dietary intakes (baseline, cumulative average, and most recent) of iron, copper, and zinc were calculated from repeated food frequency questionnaires; a modified Poisson regression model with a robust error estimator was conducted. In men, positive associations between T2D and baseline dietary intake of Cu and Zn, cumulative average dietary intake of Fe (total and animal-based), Cu and Zn, and most recent dietary intake of Fe (total, plant-based, and animal-based), Cu, and Zn [most recent diet: for total Fe, IRR(95%CI) = 1.93 (1.41-2.64); for plant-based Fe, 1.56 (1.15-2.11); for animal-based Fe, 1.44 (1.09-1.90); for Cu, 3.17 (2.33-4.30); for Zn, 2.18 (1.64-2.89)] were observed, where as in women, there were positive associations of only cumulative average dietary Zn intake and most recent dietary intake of plant-based Fe, Cu, and Zn [most recent diet: for plant-based Fe, 1.30 (1.01-1.68); for Cu, 1.62 (1.27-2.08); for Zn, 2.07 (1.61-2.66)]. CONCLUSION: Dietary intakes of iron (total, plant-based, and animal-based), copper, and zinc may be positively associated with T2D risk. These positive associations are predominantly observed in most recent diet and appear to be stronger compared to baseline and cumulative average diet.

Clinical effectiveness of ferric carboxymaltose (iv) versus iron sucrose (iv) in treatment of iron deficiency anaemia in pregnancy: A systematic review and meta-analysis.

BACKGROUND OBJECTIVES: Iron deficiency anaemia (IDA) during pregnancy is treated with oral and parenteral iron. The objective of this review was to compare the clinical effectiveness, safety, pregnancy and neonatal outcomes of intravenous (iv) ferric carboxymaltose (FCM) and iv iron sucrose (IS) in treating IDA in pregnancy. METHODS: The Department of Health Research funded this study. PubMed, Cochrane Library, EMBASE and Scopus were searched to include studies published till November 2022. The protocol was registered in PROSPERO (CRD42022306092). Pregnant women (15-49 yr) in second and third trimesters, diagnosed with moderate-to-severe iron deficiency anaemia, treated with either of the drugs were included. The included studies were critically assessed using appropriate tools. We conducted a qualitative synthesis of the studies and meta-analysis for improvement in haematological parameters and incidence of adverse events. RESULTS: A total of 18 studies were included. The risk of bias was low to moderate. A rise in haemoglobin up to four weeks was higher with FCM than IS by 0.57 (0.24, 0.9) g/dl. Intravenous FCM is associated with fewer adverse events than IS [pooled odds ratio: 0.5 (0.32, 0.79)]. The included studies had limited evidence on pregnancy and neonatal outcomes after iv iron treatment. INTERPRETATION CONCLUSIONS: Intravenous FCM is effective and safer than intravenous IS in terms of haematological parameters, in treating IDA in pregnancy. Further research is required on the effects of iv FCM and iv IS on the pregnancy and neonatal outcomes when used for treating IDA in pregnancy.

Role of mineral nutrients other than iron in pregnancy: under recognized opportunities to improve maternal/fetal outcomes: a literature review.

BACKGROUND: Anemia during pregnancy is an important global health concern, affecting 40% of women worldwide, and iron deficiency shares a significant proportion of the burden. From conception to birth, pregnancy is a period when women undergo metabolic and physiological changes. The nutritional needs are higher during pregnancy; thus, adequate nutrition is essential to maintain fetal growth and development. However, adverse effects due to deficiency in nutrition during pregnancy can result in maternal, fetal and neonatal complications. Despite the multifactorial etiology of anemia, iron deficiency is assumed as the primary cause of anemia during pregnancy and hence, mitigation strategy pivots around it for anemia management. Therefore, excluding other contributors, a single-micronutrient approach with iron supplements remains a myopic approach and this can exacerbate iron deficiency anemia. Micronutrient deficiencies are of particular concern as they may pose a silent threat to the survival and well-being of reproductive-age women and their infants. AIM: Micronutrients, especially trace minerals, play a myriad of roles in pregnancy, and the lack of each one causes adverse complications to both the mother and the fetus. In this review paper, we attempt to piece together available information regarding the adverse effects of abnormal trace mineral levels along with iron deficiency on the mother and the fetus. METHOD: A non-systematic literature search in PubMed, Google Scholar, and the Cochrane databases, for publications on minerals and vitamins during pregnancy and the possible influence of supplements on pregnancy outcomes. CONCLUSION: Micronutrient deficiency exacerbates the pregnancy-induced anemia and other adverse birth outcomes. Micronutrient supplementation during pregnancy can combat anemia as well as reduce a number of adverse pregnancy outcomes in a comprehensive manner.

Evaluation of the Olo Prenatal Nutrition Follow-up Care for Vulnerable Pregnant Women.

Olo nutritional follow-up care offers vulnerable pregnant women food vouchers, multivitamin supplements, tools, and nutritional counselling to support healthy pregnancy outcomes.Purpose: To evaluate the contribution of Olo follow-up care to nutritional intakes and eating practices, as well as to assess the programme-related experience of participants.Methods: Participants (n = 30) responded to questionnaires and web-based 24-hour dietary recalls and participated in a semi-structured interview (n = 10).Results: Olo follow-up care reduced the proportion of participants below the recommended intake for groups for many micronutrients, with the greatest reduction for folate (by 96.7%), vitamin D (by 93.3%), iron (by 70.0%), calcium (by 50.0%), and zinc (by 30.0%), mainly due to the prenatal multivitamin supplements. Most participants (96.7%) did not follow Olo's typical recommendations but, if they had, hypothetically they would have consumed an average of 746 additional calories per day and be above the recommendations for excessive intakes of folic acid and iron (100% and 33.3%, respectively). More than half of the participants were moderately to severely food insecure. Olo contributed to reducing the impact of isolation and increased food accessibility and budget flexibility among participants.Conclusion: Olo follow-up care helped reduce the proportion of women below the recommended intake for micronutrients, but revising the food offered and strategies to address food insecurity may be necessary.

Prenatal iron supplementation adjusted to maternal iron stores reduces behavioural problems in 4-year-old children.

Prenatal iron supplementation improves children's health and cognitive performance, but few studies explore behavioural development. This study assessed the effects of adjusting prenatal iron supplementation to maternal iron stores during early pregnancy on children's behavioural problems. Randomized controlled trial conducted in Tarragona (Spain) involving 230 nonanaemic pregnant women and their children after a 4-year follow-up. Based on haemoglobin (Hb) levels before gestational week (GW) 12, women receive different iron doses: those with Hb = 110-130 g/L were randomized to receive 80 or 40 mg/day and those with Hb > 130 g/L were randomized to receive 20 or 40 mg/day. Maternal iron stores at GW12 were classified using serum ferritin (SF) as low (SF < 15 µg/L), normal (SF = 15-65 µg/L), and normal-high (SF > 65 µg/L). Children's behaviour was assessed by parents using the Child Behaviour Checklist for ages 1.5-5 years and the Behaviour Rating Inventory of Executive Function-Preschool Version, and by teachers using the Teacher's Report Form for ages 1.5-5 years. Multivariable regression models were performed. Taking 80 mg/day of iron improved child behaviour when women had low iron stores but worsened it when mothers had normal-high iron stores, except for depressive and attention/hyperactivity problems. Taking 20 mg/day of iron improved behaviour only in those children whose mothers had SF > 65 µg/L in early pregnancy. Additionally, executive functioning improved at high doses of prenatal iron when maternal baseline SF < 15 µg/L. Adjusting prenatal iron supplementation to both maternal baseline Hb levels and iron stores reduces behavioural problems in 4-year-old children.

Sensory evaluations of a novel iron and zinc-enriched powder for the potential treatment and prevention of iron deficiency in women of reproductive age.

Iron deficiency (ID) and ID with anaemia (IDA) are serious global health problems that disproportionately affect women aged 15-49 years. Although food fortification is one of the most effective and sustainable ways to combat nutritional deficiencies, iron remains one of the most difficult micronutrients to fortify, given its tendency to react strongly with food constituents. Therefore, it is important to assess the sensory properties of foods fortified with iron to determine the acceptability and palatability in target populations. We aimed to determine the palatability and acceptability of a novel iron and zinc-enriched powder fortified in tap water by conducting sensory evaluations in 35 women of reproductive age using a 9-point hedonic scale, where participants rated the sensory properties of six samples containing different amounts of the active or placebo powder. We found significant differences between samples reconstituted at 1, 2, and 3 g/L for sensory properties, including overall taste. Participants were found to be more willing to drink the mineral-enriched powder when prepared at the lowest concentration (1 g/L) compared to higher concentrations. Our results provide important insight into the sensory qualities of a novel formulation of an iron and zinc-enriched powder for at-home fortification and indicate consumer acceptability in reproductive-aged women, a key group at risk for ID/IDA. If found to improve iron status, novel treatments like this product will contribute to global efforts to develop safe, acceptable and sustainable interventions for ID and IDA.

Fortified balanced energy-protein supplementation during pregnancy and lactation and infant growth in rural Burkina Faso: A 2 × 2 factorial individually randomized controlled trial.

BACKGROUND: Optimal nutrition is crucial during the critical period of the first 1,000 days from conception to 2 years after birth. Prenatal and postnatal supplementation of mothers with multimicronutrient-fortified balanced energy-protein (BEP) supplements is a potential nutritional intervention. However, evidence on the long-term effects of BEP supplementation on child growth is inconsistent. We evaluated the efficacy of daily fortified BEP supplementation during pregnancy and lactation on infant growth in rural Burkina Faso. METHODS AND FINDINGS: A 2 × 2 factorial individually randomized controlled trial (MISAME-III) was implemented in 6 health center catchment areas in Houndé district under the Hauts-Bassins region. From October 2019 to December 2020, 1,897 pregnant women aged 15 to 40 years with gestational age <21 completed weeks were enrolled. Women were randomly assigned to the prenatal intervention arms receiving either fortified BEP supplements and iron-folic acid (IFA) tablets (i.e., intervention) or IFA alone (i.e., control), which is the standard of care during pregnancy. The same women were concurrently randomized to receive either of the postnatal intervention, which comprised fortified BEP supplementation during the first 6 months postpartum in combination with IFA for the first 6 weeks (i.e., intervention), or the postnatal control, which comprised IFA alone for 6 weeks postpartum (i.e., control). Supplements were provided by trained village-based project workers under direct observation during daily home visits. We previously reported the effect of prenatal BEP supplementation on birth outcomes. The primary postnatal study outcome was length-for-age z-score (LAZ) at 6 months of age. Secondary outcomes were anthropometric indices of growth (weight-for length and weight-for-age z-scores, and arm and head circumferences) and nutritional status (prevalence rates of stunting, wasting, underweight, anemia, and hemoglobin concentration) at 6 months. Additionally, the longitudinal prevalence of common childhood morbidities, incidence of wasting, number of months of exclusive breastfeeding, and trajectories of anthropometric indices from birth to 12 months were evaluated. Prenatal BEP supplementation resulted in a significantly higher LAZ (0.11 standard deviation (SD), 95% confidence interval (CI) [0.01 to 0.21], p = 0.032) and lower stunting prevalence (-3.18 percentage points (pp), 95% CI [-5.86 to -0.51], p = 0.020) at 6 months of age, whereas the postnatal BEP supplementation did not have statistically significant effects on LAZ or stunting at 6 months. On the other hand, postnatal BEP supplementation did modestly improve the rate of monthly LAZ increment during the first 12 months postpartum (0.01 z-score/month, 95% CI [0.00 to 0.02], p = 0.030), whereas no differences in growth trajectories were detected between the prenatal study arms. Furthermore, except for the trend towards a lower prevalence of underweight found for the prenatal BEP intervention at 6 months (-2.74 pp, 95% CI [-5.65 to 1.17], p = 0.065), no other secondary outcome was significantly affected by the pre- or postnatal BEP supplementation. CONCLUSIONS: This study provides evidence that the benefits obtained from prenatal BEP supplementation on size at birth are sustained during infancy in terms of linear growth. Maternal BEP supplementation during lactation may lead to a slightly better linear growth towards the second half of infancy. These findings suggest that BEP supplementation during pregnancy can contribute to the efforts to reduce the high burden of child growth faltering in low- and middle-income countries. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03533712.

Poor recognition and undertreatment of anemia in patients with chronic kidney disease managed in primary care.

BACKGROUND: Anemia is a common complication of chronic kidney disease (CKD), but limited awareness and treatment options may hinder its management among CKD patients followed in primary care. METHODS: We evaluated adults with CKD stages 3-5 attending primary care in Stockholm, Sweden, 2012-2018. We assessed the incidence of anemia, clinical reactions, and association with subsequent major adverse cardiovascular events (MACE) and death. RESULTS: We identified 45,637 patients with CKD stages 3-5 free from anemia (mean age 78 years; 64% females; 79% CKD stage 3b). During a median follow-up of 2.4 years, 26% of patients developed anemia, and 10.4% developed severe anemia (hemoglobin <10 g/dL). Within 6 months from the anemia event, iron tests were infrequent; ferritin and transferrin saturation were tested in 27% and 11% of anemia cases, respectively, and 49% and 24% of severe anemia cases. Few patients were recognized with a clinical diagnosis (15% of anemia cases; 68% of severe anemias). Only 19% of patients with anemia received treatment, primarily iron (10%) and blood transfusions (7%); erythropoietin-stimulating agent use was anecdotal (∼1%). Treatment rates for severe anemia were higher, but 43% of patients still failed to receive treatment. Developing anemia was associated with a higher risk of MACE and death. CONCLUSION: Anemia was common and associated with adverse outcomes among patients with CKD stages 3-5 managed in primary care. Iron stores were infrequently tested, and a large proportion of patients with anemia remained untreated/under-recognized.

Ferric Carboxymaltose Versus Ferrous Fumarate in Anemic Children with Inflammatory Bowel Disease: The POPEYE Randomized Controlled Clinical Trial.

OBJECTIVE: To determine whether intravenous (IV) or oral iron suppletion is superior in improving physical fitness in anemic children with inflammatory bowel disease (IBD). STUDY DESIGN: We conducted a clinical trial at 11 centers. Children aged 8-18 with IBD and anemia (defined as hemoglobin [Hb] z-score < -2) were randomly assigned to a single IV dose of ferric carboxymaltose or 12 weeks of oral ferrous fumarate. Primary end point was the change in 6-minute walking distance (6MWD) from baseline, expressed as z-score. Secondary outcome was a change in Hb z-score from baseline. RESULTS: We randomized 64 patients (33 IV iron and 31 oral iron) and followed them for 6 months. One month after the start of iron therapy, the 6MWD z-score of patients in the IV group had increased by 0.71 compared with -0.11 in the oral group (P = .01). At 3- and 6-month follow-ups, no significant differences in 6MWD z-scores were observed. Hb z-scores gradually increased in both groups and the rate of increase was not different between groups at 1, 3, and 6 months after initiation of iron therapy (overall P = .97). CONCLUSION: In this trial involving anemic children with IBD, a single dose of IV ferric carboxymaltose was superior to oral ferrous fumarate with respect to quick improvement of physical fitness. At 3 and 6 months after initiation of therapy, no differences were discovered between oral and IV therapies. The increase of Hb over time was comparable in both treatment groups. TRIAL REGISTRATION: NTR4487 [Netherlands Trial Registry].

Supplementation With Iron Syrup or Iron-Containing Multiple Micronutrient Powders Alters Resting Brain Activity in Bangladeshi Children.

BACKGROUND: Anemia and iron deficiency have been associated with poor child cognitive development. A key rationale for the prevention of anemia using supplementation with iron has been the benefits to neurodevelopment. However, little causal evidence exists for these gains. OBJECTIVES: We aimed to examine effects of supplementation with iron or multiple micronutrient powders (MNPs) on brain activity measures using resting electroencephalography (EEG). METHODS: Children included in this neurocognitive substudy were randomly selected from the Benefits and Risks of Iron Supplementation in Children study, a double-blind, double-dummy, individually randomized, parallel-group trial in Bangladesh, in which children, starting at 8 mo of age, received 3 mo of daily iron syrup, MNPs, or placebo. Resting brain activity was recorded using EEG immediately after intervention (month 3) and after a further 9-month follow-up (month 12). We derived EEG band power measures for delta, theta, alpha, and beta frequency bands. Linear regression models were used to compare the effect of each intervention with that of placebo on the outcomes. RESULTS: Data from 412 children at month 3 and 374 at month 12 were analyzed. At baseline, 43.9% were anemic and 26.7% were iron deficient. Immediately after intervention, iron syrup, but not MNPs, increased the mu alpha-band power, a measure that is associated with maturity and the production of motor actions (iron vs. placebo: mean difference = 0.30; 95% CI: 0.11, 0.50 µV2; P = 0.003; false discovery rate adjusted P = 0.015). Despite effects on hemoglobin and iron status, effects were not observed on the posterior alpha, beta, delta, and theta bands, nor were effects sustained at the 9-month follow-up. CONCLUSIONS: The effect size for immediate effects on the mu alpha-band power is comparable in magnitude with psychosocial stimulation interventions and poverty reduction strategies. However, overall, we did not find evidence for long-lasting changes in resting EEG power spectra from iron interventions in young Bangladeshi children. This trial was registered at www.anzctr.org.au as ACTRN12617000660381.

Improving Anemia Assessment in Clinical and Public Health Settings.

We aim to provide a practical approach to assess anemia and its primary causes, both in clinical settings and in the context of public health programs. Anemia remains a global challenge; thus, to achieve goals for anemia reduction and assess progress, standardized approaches are required for the assessment of anemia and its causes. We first provide a brief review of how to assess anemia, based on hemoglobin concentrations and cutoffs that correspond to age, sex, and physiologic status. Next, we discuss how to assess the likely causes of anemia in different settings. The causes of anemia are classified as non-nutritional (for example, because of infection, inflammation, blood loss, or genetic disorders) or nutrition-specific (for example, because of deficiencies of iron, vitamin A, riboflavin, vitamin B12, or folate). There is an important overlap between these 2 categories, such as the increased likelihood of iron deficiency in the context of inflammation. Given the multifaceted nature of anemia etiology, we introduce a framework for anemia assessment based on the "ecology of anemia," which recognizes its many overlapping causes. This conceptual framework is meant to inform what data on anemia causes may need to be collected in population surveys. The framework has a supporting table with information on the diagnostic tests, biomarkers and proposed cutoffs, characteristics, and feasibility of collecting the myriad information that can help elucidate the anemia etiology. We also provide examples of how this framework can be applied to interpret the anemia risk factor data from population-based surveys that can inform decisions about context-specific interventions. Finally, we present research gaps and priorities related to anemia assessment.

Safety, pharmacokinetics, and pharmacodynamics of intravenous ferric carboxymaltose in children with iron deficiency anemia.

BACKGROUND: Iron deficiency is the primary cause of anemia in children. Intravenous (IV) iron formulations circumvent malabsorption and rapidly restore hemoglobin. METHODS: This Phase 2, non-randomized, multicenter study characterized the safety profile and determined appropriate dosing of ferric carboxymaltose (FCM) in children with iron deficiency anemia. Patients aged 1-17 years with hemoglobin <11 g/dL and transferrin saturation <20% received single IV doses of undiluted FCM 7.5 mg/kg (n = 16) or 15 mg/kg (n = 19). RESULTS: The most common drug-related treatment-emergent adverse event was urticaria (in three recipients of FCM 15 mg/kg). Systemic exposure to iron increased in a dose-proportional manner with approximate doubling of mean baseline-corrected maximum serum iron concentration (157 µg/mL with FCM 7.5 mg/kg; and 310 µg/mL with FCM 15 mg/kg) and area under the serum concentration-time curve (1901 and 4851 h·µg/mL, respectively). Baseline hemoglobin was 9.2 and 9.5 g/dL in the FCM 7.5 and 15 mg/kg groups, respectively, with mean maximum changes in hemoglobin of 2.2 and 3.0 g/dL, respectively. CONCLUSIONS: In conclusion, FCM was well tolerated by pediatric patients. Improvements in hemoglobin were greater with the higher dose, supporting use of the FCM 15 mg/kg dose in pediatric patients (Clinicaltrials.gov NCT02410213). IMPACT: This study provided information on the pharmacokinetics and safety of intravenous ferric carboxymaltose for treatment of iron deficiency anemia in children and adolescents. In children aged 1-17 years with iron deficiency anemia, single intravenous doses of ferric carboxymaltose 7.5 or 15 mg/kg increased systemic exposure to iron in a dose-proportional manner, with clinically meaningful increases in hemoglobin. The most common drug-related treatment-emergent adverse event was urticaria. The findings suggest that iron deficiency anemia in children can be corrected with a single intravenous dose of ferric carboxymaltose and support use of a 15 mg/kg dose.

Iron intake and multiple health outcomes: Umbrella review.

Iron is an essential trace element, while excess iron can lead to different levels of physical abnormalities or diseases. This umbrella review aimed to conduct a systematic evaluation of the possible relationships between iron intake and various health outcomes. We retrieved PubMed, Embase, Web of Science, Scopus, and the Cochrane Database of Systematic Reviews from inception through May 2021. A total of 34 meta-analyses with 46 unique health outcomes were identified. Heme iron intake was positively associated with nine outcomes, including colorectal cancer, type 2 diabetes mellitus, and cardiovascular disease mortality, while dietary total iron intake could decrease the risk of colorectal adenoma, esophageal cancer, coronary heart disease, and depression. Iron supplementation was a protective factor against eight outcomes. However, it was associated with decreased length and weight gain. The quality of evidence for most outcomes was "low" or "very low" with the remaining eleven as "high" or "moderate". All outcomes were categorized as class III, IV, or NS based on evidence classification. Although high iron intake has been identified to be significantly associated with a range of outcomes, firm universal conclusions about its beneficial or negative effects cannot be drawn given the low quality of evidence for most outcomes.

Effects of Hyperferritinemia on Functional Outcome in Acute Ischemic Stroke Patients with Admission Hyperglycemia.

INTRODUCTION: Hyperferritinemia, presented as elevated serum ferritin level, is an indicator of high iron status which plays roles in secondary brain injury after acute ischemic stroke (AIS). However, the effects of hyperferritinemia and poor outcomes remain uncertain. Additionally, admission hyperglycemia quite frequently accompanies AIS patients, which is associated with unfavorable outcome. Thus, we aimed to investigate the effects of hyperferritinemia on 3-month and 1-year functional outcomes in AIS patients and especially those with admission hyperglycemia. METHODS: AIS patients within 24 h of onset were enrolled at West China Hospital from October 2016 to December 2019. Serum ferritin and blood glucose levels were tested on admission. Poor functional outcome at 3 months and 1 year was defined as modified Rankin Scale score ≥3. Multivariable analysis was used to investigate the associations between hyperferritinemia and 3-month and 1-year outcomes. Subgroup analysis was performed in patients with and without hyperglycemia. RESULTS: Of 723 patients (mean age 68.11 years, 60.6% males) finally included, 347 (48.0%) had hyperferritinemia. The incidence of poor outcome was 45.2% at 3 months and 41.2% at 1 year. Patients with hyperferritinemia had a higher frequency of poor 3-month outcome (51.8% vs. 39.2%, p = 0.001) and poor 1-year outcome (46.8% vs. 36.1%, p = 0.004). In all AIS patients, hyperferritinemia was not independently associated with poor functional outcome at 3 months or 1 year after adjusting for confounders (all p > 0.05). In AIS patients with hyperglycemia, hyperferritinemia was an independent factor correlated with poor 3-month outcome (OR = 1.711, 95% CI 1.093-2.681, p = 0.019) but not with poor 1-year outcome (p > 0.05). CONCLUSIONS: High iron status, presented as hyperferritinemia, is associated with poor 3-month functional outcome in AIS patients with hyperglycemia. Evaluating serum ferritin level may be conducive to assess the risk of short-term poor outcome in AIS patients with hyperglycemia. Further studies will be required to confirm our findings.

Assessing food-based strategies to address anaemia in pregnancy in rural plains Nepal: a mixed methods study.

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.