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ObjectiveIron-containing micronutrient powders (MNPs) reduce anaemia in African infants, but the current high iron dose (12.5 mg/day) may decrease gut Bifidobacteriaceae and Lactobacillaceae, and increase enteropathogens, diarrhoea and respiratory tract infections (RTIs). We evaluated the efficacy and safety of a new MNP formula with prebiotic galacto-oligosaccharides (GOS) combined with a low dose (5 mg/day) of highly bioavailable iron.DesignIn a 4-month, controlled, double-blind trial, we randomised Kenyan infants aged 6.5–9.5 months (n=155) to receive daily (1) a MNP without iron (control); (2) the identical MNP but with 5 mg iron (2.5 mg as sodium iron ethylenediaminetetraacetate and 2.5 mg as ferrous fumarate) (Fe group); or (3) the identical MNP as the Fe group but with 7.5 g GOS (FeGOS group).ResultsAnaemia decreased by ≈50% in the Fe and FeGOS groups (p<0.001). Compared with the control or FeGOS group, in the Fe group there were (1) lower abundances of Bifidobacterium and Lactobacillus and higher abundances of Clostridiales (p<0.01); (2) higher abundances of virulence and toxin genes (VTGs) of pathogens (p<0.01); (3) higher plasma intestinal fatty acid-binding protein (a biomarker of enterocyte damage) (p<0.05); and (4) a higher incidence of treated RTIs (p<0.05). In contrast, there were no significant differences in these variables comparing the control and FeGOS groups, with the exception that the abundance of VTGs of all pathogens was significantly lower in the FeGOS group compared with the control and Fe groups (p<0.01).ConclusionA MNP containing a low dose of highly bioavailable iron reduces anaemia, and the addition of GOS mitigates most of the adverse effects of iron on the gut microbiome and morbidity in African infants.Trial registration numberNCT02118402.

Although iron is commonly used to correct iron deficiency anemia (IDA) in chronic kidney disease (CKD), its effect on kidney function is unclear. To assess this, we randomly assigned patients with stage 3 and 4 CKD and IDA to either open-label oral ferrous sulfate (69 patients to 325 mg three times daily for 8 weeks) or intravenous iron sucrose (67 patients to 200 mg every 2 weeks, total 1 g). The primary outcome was the between-group difference in slope of measured glomerular filtration rate (mGFR) change over two years. The trial was terminated early on the recommendation of an independent data and safety monitoring board based on little chance of finding differences in mGFR slopes, but a higher risk of serious adverse events in the intravenous iron treatment group. mGFR declined similarly over two years in both treatment groups (oral -3.6 ml/min per 1.73 m2, intravenous -4.0 ml/min per 1.73 m2, between-group difference -0.35 ml/min per 1.73 m2; 95% confidence interval -2.9 to 2.3). There were 36 serious cardiovascular events among 19 participants assigned to the oral iron treatment group and 55 events among 17 participants of the intravenous iron group (adjusted incidence rate ratio 2.51 (1.56–4.04)). Infections resulting in hospitalizations had a significant adjusted incidence rate ratio of 2.12 (1.24–3.64). Thus, among non-dialyzed patients with CKD and IDA, intravenous iron therapy is associated with an increased risk of serious adverse events, including those from cardiovascular causes and infectious diseases.

Ferric carboxymaltose (FCM) is widely used to correct anemia and replenish iron stores rapidly, particularly in Western populations. However, lower doses of FCM are typically used in East Asia, with limited research on their effectiveness, especially in postpartum women. This randomized controlled trial aimed to assess the efficacy of low-dose FCM compared with oral ferrous sulfate in increasing postpartum hemoglobin (Hb) levels and replenishing iron stores in East Asian women. Sixty postpartum women with Hb levels < 10 g/dL and serum ferritin ≤ 30 ng/mL were randomized to receive either intravenous FCM (500 mg at baseline and 2 weeks) or oral ferrous sulfate (210 mg daily for 4 weeks). The primary outcome was the increase in Hb levels at 2 weeks post-enrollment. Secondary outcomes included serum ferritin, transferrin saturation, the Edinburgh Postnatal Depression Scale (EPDS) score, and adverse events at 4 weeks. The FCM group demonstrated a significantly greater increase in Hb levels at 2 weeks (mean difference 0.42 g/dL; 95% CI: 0.12–0.72; P =  0.006), with markedly higher ferritin (adjusted mean difference 356.0 ng/mL; 95% CI: 321.0–403.0; P <  0.001) and transferrin saturation (adjusted mean difference 10.76%; 95% CI: 4.20–17.31; P =  0.002) at 4 weeks. Although there was no significant difference in final Hb levels at 4 weeks (mean difference 0.36 g/dL; 95% CI: -0.01–0.72; P =  0.055), the FCM group had a lower median EPDS score (median difference -3.0; 95% CI: -5.0 to -1.0; P =  0.002) and fewer gastrointestinal side effects, including constipation and nausea. Hypophosphatemia occurred asymptomatically in three patients in the FCM group. These findings suggest that low-dose FCM infusion is highly effective in increasing Hb levels at 2 weeks post-enrollment, with fewer gastrointestinal side effects and higher ferritin levels observed at 4 weeks post-enrollment compared with oral ferrous sulfate. This study was registered at the UMIN Clinical Trials Registry, which meets the requirements of the ICMJE, on December 1, 2021 (ID: UMIN000046049).

Fe fortification of wheat flour was proposed in Haiti to combat Fe deficiency, but Fe bioavailability from fortificants has never been investigated in Haitian women or preschool children, two key target groups. We aimed to investigate the bioavailability of ferrous fumarate (FeFum), NaFeEDTA and their combination from fortified wheat flour. We recruited twenty-two healthy mother–child pairs in Port au Prince, Haiti, for an Fe-absorption study. We administered stable Fe isotopes as FeFum or NaFeEDTA individually in low-extraction wheat flour bread rolls consumed by all participants in a randomised, cross-over design. In a final, identical meal, consumed only by the women, FeFum+NaFeEDTA was administered. We measured Fe absorption by using erythrocyte incorporation of stable isotopes 14 d after consumption of each meal, and determined Fe status, inflammatory markers and Helicobacter pylori infection. Fe absorption (geometric mean was 9·24 (95 % CI 6·35, 13·44) and 9·26 (95 % CI 7·00, 12·31) from FeFum and 13·06 (95 % CI 9·23, 19·10) and 12·99 (95 % CI 9·18, 18·39) from NaFeEDTA in mothers and children, respectively (P<0·05 between compounds). Fe absorption from FeFum+NaFeEDTA was 11·09 (95 % CI 7·45, 17·34) and did not differ from the other two meals. H. pylori infection did not influence Fe absorption in children. In conclusion, in Haitian women and children, Fe absorption from NaFeEDTA was 40 % higher than from FeFum, and the combination FeFum+NaFeEDTA did not significantly increase Fe absorption compared with FeFum alone. In the context of Haiti, where the high costs of NaFeEDTA may not be affordable, the use of FeFum at 60 mg Fe/kg flour may be a preferable, cost-effective fortification strategy.

Anemia is a common complication of inflammatory bowel diseases (IBD) This multicenter study tested the noninferiority and safety of a new intravenous iron preparation, ferric carboxymaltose (FeCarb), in comparison with oral ferrous sulfate (FeSulf) in reducing iron deficiency anemia (IDA) in IBD. Two hundred patients were randomized in a 2:1 ratio (137 FeCarb:63 FeSulf) to receive FeCarb (maximum 1,000 mg iron per infusion) at 1-wk intervals until the patients' calculated total iron deficit was reached or FeSulf (100 mg b.i.d.) for 12 wk. The primary end point was change in hemoglobin (Hb) from baseline to week 12. The median Hb improved from 8.7 to 12.3 g/dL in the FeCarb group and from 9.1 to 12.1 g/dL in the FeSulf group, demonstrating noninferiority (P= 0.6967). Response (defined as Hb increase of >2.0 g/dL) was higher for FeCarb at week 2 (P= 0.0051) and week 4 (P= 0.0346). Median ferritin increased from 5.0 to 323.5 mug/L at week 2, followed by a continuous decrease in the FeCarb group (43.5 mug/L at week 12). In the FeSulf group, a moderate increase from 6.5 to 28.5 mug/L at week 12 was observed. Treatment-related adverse events (AEs) occurred in 28.5% of the FeCarb and 22.2% of the FeSulf groups, with discontinuation of study medication due to AEs in 1.5% and 7.9%, respectively. FeCarb is effective and safe in IBD-associated anemia. It is noninferior to FeSulf in terms of Hb change over 12 wk, and provides a fast Hb increase and a sufficient refill of iron stores.

Oral iron preparations are used as first-line treatment for iron deficiency anemia (IDA), but their gastrointestinal side effects prevent patients from appropriate adherence. We recently conducted a randomized, double-blind, phase 3 non-inferiority study to evaluate the efficacy and safety of two dosages of ferric citrate hydrate (FC) compared with sodium ferrous citrate (SF) in patients with IDA. FC at both 500 and 1000 mg/day was non-inferior to SF at 100 mg/day in terms of the change in the hemoglobin concentration at Week 7 from baseline. Logistic regression analysis suggested that the cumulative proportion of patients who achieved the target hemoglobin concentration (≥ 13.0 g/dL in male patients and ≥ 12.0 g/dL in female patients) at Week 7 was highest among those treated with FC at 1000 mg/day, followed by SF at 100 mg/day and FC at 500 mg/day. Both dosages of FC were well tolerated in patients with IDA. The incidences of nausea and vomiting were significantly lower in the FC treatment groups than in the SF group. In conclusion, FC has potential to be an oral iron preparation with sufficient efficacy for the treatment of IDA and a lower risk of nausea and vomiting.

IntroductionPostpartum anaemia is often caused by iron deficiency with onset during the antepartum period and can be exacerbated by excessive blood loss at birth. Its prevalence is estimated as 50–80% in low-income and middle-income countries. It poses adverse consequences on the mother and negatively impacts her ability to care for her newborn. Prompt treatment of postpartum anaemia is thus important. Adherence to oral iron is reportedly low in Nigeria due to its side effects and forgetfulness by the mothers. Intravenous iron such as ferric carboxymaltose, given as a single dose, might help overcome adherence issues, but investigation in a high-quality randomised control trial in Nigeria is first required while evaluation of challenges around its implementation is also warranted.ObjectiveTo determine the clinical effectiveness, tolerability and safety, of using intravenous ferric carboxymaltose (intervention) vs oral ferrous sulphate (control) for treating moderate to severe iron deficiency anaemia in postpartum women and to evaluate implementation of ferric carboxymaltose in treating postpartum anaemia in Nigeria.Methods and analysisThis study is an open-label randomised controlled trial with a concurrent implementation study. It is a hybrid type 1 effectiveness-implementation design conducted in four states across Northern and Southern Nigeria. A total of 1400 eligible and consenting women with postpartum moderate to severe anaemia (haemoglobin concentration <100 g/L) will be randomised to intravenous ferric carboxymaltose; a single dose at 20 mg/kg to a maximum of 1000 mg infusion administered at enrolment (intervention) or oral ferrous sulphate; 200 mg (65 mg elemental iron) two times per day from enrolment until 6 weeks postpartum (control). The primary outcome, proportion of participants who are anaemic (Hb <110 g/L) at 6 weeks postpartum will be analysed by intention-to-treat. Haemoglobin concentration, full blood count, serum iron, serum ferritin, transferrin saturation and total iron binding capacity will be measured at specific intervals. Implementation outcomes such as acceptability and feasibility of using ferric carboxymaltose for postpartum anaemia treatment in Nigeria will be assessed.Ethics and disseminationThis study is approved by the ethics committee of the teaching hospitals, Ministry of Health of the four states as required, National Health Research Ethics Committee and the drug regulatory agency, National Agency for Food and Drug Administration and Control (NAFDAC). Findings of this research will be presented at conferences and will be published in international peer-reviewed journals and shared with stakeholders within and outside Nigeria.Trial registration numberInternational standard randomised controlled trial number: ISRCTN51426226.

In patients with heart failure with reduced ejection fraction and iron deficiency, ferric carboxymaltose therapy did not appear to differ from placebo in the composite of death, heart-failure hospitalizations, or walk distance.

This study evaluates the efficacy and safety of emulsified microsomal Ferric pyrophosphate (EMFP/SunActive™ Fe, 27 mg elemental iron) versus Ferrous Ascorbate (100 mg elemental iron) in second-trimester pregnant women with iron-deficiency anemia (IDA) for 4 weeks. Pregnant women aged 20–35 years with a singleton pregnancy, hemoglobin (Hb) 9–10.5 g/dL, and ferritin < 15 mcg/L were enrolled. The test group showed zero adverse effects vs. the control group, having 11.1% adverse events. The gastrointestinal(GI) adverse symptoms, including nausea, dark stools, and hyperacidity, were reported only in the Ferrous Ascorbate group, indicating superior tolerability and safety of EMFP tablets. Both groups showed similar improvements in Hb (Δ2.63 g/dL vs. Δ2.62 g/dL) and serum ferritin (61.09% vs. 61.92%). Reticulocyte hemoglobin (RET-He) increased by 20.5% in the test group and 16.2% in the control group, with no significant difference. Clinical symptoms such as dizziness, fatigue, and palpitations improved with greater magnitude in the test group. It was inferred that the test group receiving EMFP was as effective as the control group in improving efficacy endpoints at a significantly lower dose (1/3rd dose compared to ascorbate). EMFP showed better tolerability, safety and compliance, making it a promising option for managing IDA in pregnant women.

Food fortification with iron nanoparticles (NPs) could help prevent iron deficiency anemia, but the absorption pathway and biodistribution of iron-NPs and their bioavailability in humans is unclear. Dietary non-heme iron is physiologically absorbed via the divalent metal transporter-1 (DMT1) pathway. Using radio- iron isotope labelling in mice with a partial knockdown of intestine-specific DMT1, we assessed oral absorption and tissue biodistribution of nanostructured ferric phosphate (FePO 4 -NP; specific surface area [SSA] 98 m 2 g -1 ) compared to to ferrous sulfate (FeSO 4 ), the reference compound. We show that absorption of iron from FePO 4 -NP appears to be largely DMT1 dependent and that its biodistribution after absorption is similar to that from FeSO 4 , without abnormal deposition of iron in the reticuloendothelial system. Furthermore, we demonstrate high bioavailability from iron NPs in iron deficient anemic women in a randomized, cross-over study using stable-isotope labelling: absorption and subsequent erythrocyte iron utilization from two 57 Fe-labeled FePO 4 -NP with SSAs of 98 m 2 g −1 and 188 m 2 g −1 was 2.8-fold and 5.4-fold higher than from bulk FePO 4 with an SSA of 25 m 2 g −1 ( P  < 0.001) when added to a rice and vegetable meal consumed by iron deficient anemic women. The FePO 4 -NP 188 m 2 g -1 achieved 72% relative bioavailability compared to FeSO 4 . These data suggest FePO 4 -NPs may be useful for nutritional applications.