Improving the Gastric Resilience of Ferritin Nanocages by Fabrication with Gelatin for the Development of Oral Iron Supplements.

Iron deficiency anemia during pregnancy can increase the risks of low birth weight infant, premature birth, and impaired fetal growth. The objective of this research is to investigate the difference effect between oral and parenteral iron supplementation on body weights of the infant of anemic pregnant rat. This research used the experimental laboratory research method with the randomized controlled trial design. Thirty rats were divided into three groups and each group consisted of 10 rats. Group I was given an oral iron supplementation, group II was given parenteral iron supplementation, and group III as control group was not given any of such supplementations. This research was conducted until the mother rat gave birth, observed was body weights all of the infant rats with digital scales. The data of the research were analyzed by using Kruskal Wallis then Mann Whitney formula. The results of Kruskal Wallis that the comparisons of the average of groups I, II, and III for body weights of the infant are 6.09±0.40 g: 6.59±0.49 g: 5.81±0.39 g (p<0.001), the results of Mann Whitney that there are a difference body weights of the infant (p<0.001) between oral and parenteral iron suplementation. Based on the results of the research a conclusion is drawn that there is a difference in the body weights of the infant between oral and parenteral iron supplementation. The average body weights of the infant in the parenteral iron supplementation are better than those in the oral iron supplementation. Keywords : Iron supplementation, oral, parenteral, pregnancy, anemic rat, body weights of the infant.

Anemia and iron deficiency during pregnancy have been associated with preterm birth and neonatal complications. However, the evidence on whether intravenous or oral supplementation should be used has been conflicting. The aim was to assess the effectiveness of intravenous iron compared to oral iron supplementation on objective neonatal outcomes. We conducted a systematic review and meta-analysis of randomized controlled trials. Two databases were searched in November 2024 and the search was updated in February 2025. The main outcomes were the rate of preterm birth, stillbirths, and neonatal mortality. Random-effect meta-analysis was used to calculate risk ratios (RR) with 95% confidence intervals (CI). Evidence certainty was assessed according to GRADE. A total of 375 studies were screened and finally 15 were included. Seven studies with 8431 pregnancies analyzed the risk of preterm birth, and the risk appeared to be similar in both groups (RR 0.96, CI 0.86 to 1.07; moderate certainty evidence). Five studies with 8639 pregnancies analyzed the risk of stillbirth and found no difference (RR 0.85, CI 0.64 to 1.13; low certainty evidence). The neonatal mortality rate was 2.0% in the intravenous iron group, and 2.3% in the oral iron group (RR 0.90, CI 0.66 to 1.22; low certainty evidence). Cord hemoglobin levels were comparable between the study groups (mean difference 0.05 g/l, CI −0.33 to 0.24; low certainty evidence), and ferritin levels were slightly higher in the intravenous group (mean difference 19 µg/l, CI 0.5 to 38; low certainty evidence). Conclusions: Neonatal clinical outcomes did not differ between intravenous and oral iron supplementation treatment in pregnancy. A higher ferritin level in umbilical cord blood was found in the intravenous iron supplementation group, but the clinical relevance of this difference is unknown. Based on the results of this study, oral iron supplementation is a sufficient way to treat maternal iron deficiency, when focusing on objective neonatal outcomes.Trial registration: PROSPERO 2024 CRD42024615533 Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024615533.What is Known:• Iron-deficiency anemia during pregnancy is associated with preterm birth and neonatal complications.• Intravenous iron increases maternal hemoglobin faster than oral iron, but benefits for neonatal outcomes have been unclear.What is New:• This systematic review and meta-analysis shows that neonatal outcomes—including preterm birth, stillbirth, and mortality—do not differ between intravenous and oral iron supplementation.• Intravenous iron yields higher cord ferritin, but its clinical relevance remains uncertain.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00431-025-06522-w.

Background/Aims Iron deficiency anaemia is considered a major global public health challenge, especially in developing countries, with pregnant women being most affected. In Ghana, the prevalence of anaemia in pregnancy is relatively high, particularly in the Tain district. This has been attributed to problems with compliance to oral iron and folic acid supplementation. The aim of this study was to assess personal factors associated with compliance with oral iron supplementation in rural areas of the Tain district. Methods A cross-sectional design was used for this study, which collected quantitative data from 480 pregnant women. Ten health facilities were selected, with proportional allocation of the sample to each facility. Simple random sampling was used to select pregnant women in the clinical setting. A structured questionnaire was used to collect participants' data and descriptive and inferential statistics were applied. Results Only a third (34%) of respondents complied with oral iron supplementation. Cohabiting with a partner (P=0.003), having no formal or only primary level education (P=0.009), having a partner with middle school or junior high school level education (P=0.014) and being in the first trimester (P&lt;0.001) were significantly associated with compliance. Conclusions Compliance with oral iron supplementation was low. Health education on iron supplementation should be strengthened by targeting pregnant women at risk of non-compliance. This education should be carried out by midwives during routine antenatal visits.

Using hemoglobin concentration ([Hb]) to diagnose borderline iron deficiency and monitor the progress of its treatment is difficult because of the confounding effects of plasma volume. Because hemoglobin mass (Hbmass) is not affected by plasma volume, it may be a more sensitive parameter. The aim of this study was to monitor Hbmass, iron storage, and maximal oxygen consumption (V˙O2max) during and after oral iron therapy in subjects with severe and moderate iron deficiency. Three groups of female recreational athletes were monitored for at least 22 wk, as follows: 1) severe iron deficiency group (SID) (n = 8; ferritin, ≤12 ng·mL), 2) moderate iron deficiency group (MID) (n = 14; ferritin, ≤25 ng·mL), and 3) control group (n = 8; ferritin, >25 ng·mL). Hbmass and iron status were determined before, during, and up to 12 wk after at least 10 wk of oral iron supplementation. In total, five V˙O2max tests were performed before, during, and after the supplementation period. Hbmass increased markedly in the SID group (15.6% ± 11.0%, P < 0.001) and slightly in the MID group (2.2% ± 3.7%, P < 0.05) by the end of the supplementation period and remained at this level for the following 12 wk. [Hb] and Hbmass were similarly affected, but Hbmass was more closely related to mean corpuscular volume and mean corpuscular hemoglobin than [Hb]. The SID group incorporated 534 ± 127 mg of iron into ferritin and hemoglobin, whereas the MID group incorporated 282 ± 68 mg of iron. V˙O2max increased only in the SID group by 0.20 ± 0.18 L·min (P < 0.05) and was closely related to Hbmass (P < 0.01). Hbmass is a sensitive tool for monitoring recovery from iron deficiency anemia and assessing the effectiveness of iron supplementation in individuals with severe or moderate iron deficiency.

Aim: To compare the efficacy of oral and intravenous iron supplements in the management of anemia in pregnancy. Materials and Methods: Antenatal women between 24 to 34 weeks period of gestation (POG) with mild to moderate anemia were included. They were randomly divided into two groups where Group A - supplemented with oral iron (ferrous sulfate 300mg) and Group B - supplemented with intravenous iron sucrose 200mg. Where Intravenous iron sucrose of 200mg of 4 doses 2 weeks apart (i.e. 24 weeks POG, 26 weeks POG, 28 weeks POG, 30 weeks POG) were infused. Whereas oral iron ferrous sulfate 300mg per day (i.e. from 24 weeks POG – 34 weeks POG) in mild to moderate anemia patients were administered. Results: The mean difference of the haemoglobin between before and after administration of the intravenous iron supplements was observed to very high (2.13 g/dl) when compared to the mean difference of the haemoglobin between before and after administration of the oral iron supplements (0.97 g/dl). The mean difference of the ferritin between before and after administration of the intravenous iron supplements was observed to very high (46.9 ?g/L) when compared to the mean difference of the ferritin between the before and after administration of the oral iron supplements (21.24 ?g/L). Conclusion: In this study, we observed an increase in the mean values of haemoglobin and ferritin after the administration of both intravenous and oral iron supplements. When comparing the mean differences of haemoglobin and ferritin of intravenous iron supplements with oral iron supplements, a significant increase in the values of haemoglobin and ferritin was observed among the pregnant women who were administered with intravenous iron supplements when compared to the pregnant women who were administered with oral iron supplements.

It remains uncertain whether vitamin C routinely used with oral iron supplements is essential for patients with iron deficiency anemia (IDA). To compare the equivalence and assess the safety of oral iron supplements plus vitamin C or oral iron supplements alone in patients with IDA. This single-center, open-label, equivalence randomized clinical trial was conducted from January 1, 2016, to December 30, 2017, in Huashan Hospital, Fudan University. Adult patients with newly diagnosed IDA were enrolled. Participants were randomly assigned (1:1) to the oral iron supplements plus vitamin C group or the oral iron supplements-only group. Data analysis was performed from March to December 2018. Patients were randomized to receive a 100-mg oral iron tablet plus 200 mg of vitamin C or a 100-mg iron tablet alone every 8 hours daily for 3 months. The primary outcome was the change in hemoglobin level from baseline to 2 weeks of treatment, and an equivalence margin of 1 g/dL in hemoglobin was chosen for the demonstration of comparable efficacy. Secondary outcomes included the change in the reticulocyte percentage after 2 weeks of treatment, the increase in hemoglobin level after 4 weeks of treatment, the increase in serum ferritin level after 8 weeks of treatment, and adverse events. Among the 440 randomized patients (220 each in the oral iron supplements plus vitamin C group and iron-only group; 426 women [96.8%]; mean [SD] age, 38.3 [11.7] years), all were assessed for the primary outcome, and 432 (98.2%) completed the trial. From baseline to the 2-week follow-up, the mean (SD) change in hemoglobin level was 2.00 (1.08) g/dL in the oral iron supplements plus vitamin C group and 1.84 (0.97) g/dL in the oral iron supplements-only group (between-group difference, 0.16 g/dL; 95% CI, -0.03 to 0.35 g/dL), thus meeting the criteria for equivalence. The mean (SD) change in serum ferritin level from baseline to 8-week follow-up was 35.75 (11.52) ng/mL in the vitamin C plus iron group and 34.48 (9.50) ng/mL in the iron-only group (between-group difference, 1.27 ng/mL; 95% CI, -0.70 to 3.24 ng/mL; P = .21). There were no significant differences between the 2 groups regarding the rates of adverse events (46 [20.9%] vs 45 [20.5%]; difference, 0.4%; 95% CI, -6.7% to 8.5%; P = .82). No patient withdrew because of adverse events. Among patients with IDA, oral iron supplements alone were equivalent to oral iron supplements plus vitamin C in improving hemoglobin recovery and iron absorption. These findings suggest that on-demand vitamin C supplements are not essential to take along with oral iron supplements for patients with IDA. ClinicalTrials.gov Identifier: NCT02631668.

Iron deficiency is the single most prevalent nutritional deficiency worldwide. It accounts for anemia in 5% of American women and 2% of American men. The goal of this review article is to assist practitioners in understanding the physiology of iron metabolism and to aid in accurately diagnosing iron deficiency anemia. The current first line of therapy for patients with iron deficiency anemia is oral iron supplementation. Oral supplementation is cheap, safe, and effective at correcting iron deficiency anemia; however, it is not tolerated by some patients and in a subset of patients it is insufficient. Patients in whom the gastrointestinal blood loss exceeds the intestinal ability to absorb iron (e.g. intestinal angiodysplasia) may develop iron deficiency anemia refractory to oral iron supplementation. This population of patients proves to be the most challenging to manage. Historically, these patients have required numerous and frequent blood transfusions and suffer end-organ damage resultant from their refractory anemia. Intravenous iron supplementation fell out of favor secondary to the presence of infrequent but serious side effects. Newer and safer intravenous iron preparations are now available and are likely currently underutilized. This article discusses the possible use of intravenous iron supplementation in the management of patients with severe iron deficiency anemia and those who have failed oral iron supplementation.

Oral iron supplements such as ferrous iron salts are major treatment agents for iron deficiency anemia (IDA) due to the convenience of large dose administration and good patient compliance. However, the gastrointestinal adverse impact caused by Fe2+ stimulus and low bioavailability severely impedes its therapeutic effects. In recent years, it has been found that nano iron-based nanoparticles with high surface-to-volume ratio and low iron ion leakage can alleviate the toxic effect and improve the gastrointestinal absorbance. For further clinical development, nano materials need to meet the pharmaceutical quality demand. Carboxymethyl cellulose (CMC) is a significant pharmaceutical ingredient applied in approved drug formulations, and polyglucosorbitol carboxymethylether (PSC) has been utilized in iron-based nanomedicine ferumoxytol synthesis, both of which can be firmly anchored on iron oxide by carboxyl chelation. In this work, iron oxide nanoparticles (NPs) modified with CMC were designed and synthesized, and the structure composition and physicochemical properties were distinctly characterized. Oral supplement effects on rat IDA were investigated and compared with other recently reported iron supplements including NPs modified with PSC. Results show that the oral nano iron supplement achieved the recovery of hemoglobin and serum iron level in only two weeks with high safety. The nano iron oxide modified with pharmaceutical excipients provides new potential approach for oral iron supplement available in clinics.

Pediatric iron deficiency anemia (IDA) is often treated with oral iron supplementation as the first-line therapy despite poor adherence. This single-institution retrospective chart review of pediatric patients was conducted to assess the safety, efficacy, and adherence of intravenous (IV) iron infusions compared to oral iron therapy in patients who had failed a trial of oral iron supplementation. We reviewed medical records of patients aged 1-21 with IDA who received at least one IV iron infusion at Cooper University Hospital between 2016 and 2021. Paired t-tests compared pre-infusion and post-infusion hematologic indices of hemoglobin (Hgb), mean corpuscular volume, red blood cell count, red cell distribution width, ferritin, total iron binding capacity, iron stores, and iron saturation. We compared adherence and adverse reactions to both oral iron supplementation and IV iron infusions using McNemar's test. A total of 107 subjects were included (mean age of 12.7 years). Hgb, ferritin, iron, and iron saturation between pre-infusion and post-final infusion significantly improved (p < 0.001). Hgb, ferritin, and iron improved when subcategorizing by race and etiology of IDA. Adherence to IV iron infusions (70.1%) was significantly greater than adherence to oral iron therapy (43.0%). There were also significantly fewer adverse effects with IV iron infusions (3.7%) compared to oral iron (77.9%). We demonstrated the safety, efficacy, and improved adherence of IV iron infusions compared to oral iron supplementation for treatment of pediatric IDA in patients who were unable to tolerate oral iron supplementation. Future studies could compare adherence to multiple doses of IV iron infusions in contrast with other single-dosing IV iron formulations.

Iron deficiency (ID) and iron deficiency anemia (IDA) are important signs of gastrointestinal (GI) hemorrhage. Therefore, the evaluation of the GI tract should be a part of the diagnostic protocol in patients with IDA. GI hemorrhage is not a disease but a symptom, which might have different underlying causes. ID and IDA have significant negative impacts on the life quality and work ability, and they may lead to frequent hospitalization, delay of discharge, and increased healthcare costs. Therefore, an optimal management of the disease causing GI hemorrhage should include iron replacement therapy, along with the treatment of the underlying condition. IDA in inflammatory bowel disease (IBD) has received particular attention owing to its high prevalence, probably due to a number of other factors such as chronic hemorrhage, reduced dietary iron intake, and impaired absorption of iron. Historically, in IBD and in patients with GI hemorrhage, the diagnosis and management of IDA have been suboptimal. Options for iron replacement include oral and intravenous (IV) iron supplementation. Oral iron supplementation frequently results in GI side effects, and theoretically, it may exacerbate IBD activity; therefore, IV iron supplementation is usually considered in patients not responding to or not complying with oral iron supplementation or patients having low hemoglobin concentration and requiring prompt iron repletion. The aim of this report was to review the diagnostic and therapeutic considerations of IDA in IBD and GI hemorrhage with a multidisciplinary group of experts and to formulate necessary practical recommendations.

AGA Clinical Practice Update on Management of Iron Deficiency Anemia: Expert Review

A Head-to-Head Comparison of the Safety and Efficacy of Ferumoxytol to Iron Sucrose for the Treatment of Iron Deficiency Anemia

Background: Anemia is an indirect cause of high maternal mortality rates worldwide characterized by low levels of hemoglobin, hepcidin, and serum ferritin. Hepcidin is a biomarker of iron metabolism in the body while ferritin acts as a store of iron. Hepcidin and ferritin levels during pregnancy will decrease. To restore the levels, supplementation is required either orally or intravenously. This study aimed to determine the effect of oral and intravenous iron supplementation on hepcidin and ferritin levels. Methods: This was an experimental laboratory study using Posttest Only Control Group Design. The sample was 24 Rattus Norvegicus divided into 4 groups: the negative control group without treatment, the positive control group given NaNo, the, P1 given oral iron supplementation, and the P2 given intravenous iron. The maintenance of the test animals in this study was carried out at the Pharmacy laboratory of Universitas Andalas Padang in June-August 2021. The experimental animals were Rattus Norvegicus Wistar females weighing 200-250 grams, aged between 3-4 months conditioned to be pregnant. The serum examination of hepcidin and ferritin levels used the ELISA method and the normality test used Shapiro Wilk. Then, the significance test used One-Way ANNOVA followed by multiple comparisons of Bonferroni types. Results: The results showed that there were significant differences (p&lt;0.05) in hepcidin levels in the positive control group, treatment group 1, treatment 2 that were 219.52 ng/ml, 220.27 ng/ml, and 221.49 ng/ml. Likewise, the ferritin levels in the positive control group, treatment 1, and treatment 2 were 5.91 ng/ml, 6.81 ng/ml and 7.72 ng/ml. Conclusion: Based on the findings, it can be concluded that oral and intravenous iron supplementation had an effect on increasing serum hepcidin and ferritin levels in Rattus norvegicus pregnant strain Wistar with anemia. Keywords: Oral iron supplementation, intravenous supplementation, hepcidin and ferritin

BackgroundPost-transplant anaemia remains a common problem after kidney transplantation, with an incidence ranging from nearly 80% at day 0 to about 25% at 1 year. It has been associated with poor graft outcome, and recently has also been shown to be associated with increased mortality.Our transplant unit routinely administers oral iron supplements to renal transplant recipients but this is frequently accompanied by side effects, mainly gastrointestinal intolerance. Intravenous iron is frequently administered to dialysis patients and we sought to investigate this mode of administration in transplant recipients after noticing less anaemia in several patients who had received intravenous iron just prior to being called in for transplantation.MethodsThis study is a single-centre, prospective, open-label, randomised, controlled trial of oral versus intravenous iron supplements in renal transplant recipients and aims to recruit approximately 100 patients over a 12-month period. Patients will be randomised to receive a single dose of 500 mg iron polymaltose (intravenous iron group) or 2 ferrous sulphate slow-release tablets daily (oral iron group). The primary outcome is time to normalisation of haemoglobin post-transplant. Prospective power calculations have indicated that a minimum of 48 patients in each group would have to be followed up for 3 months in order to have a 90% probability of detecting a halving of the time to correction of haemoglobin levels to ≥110 g/l in iron-treated patients, assuming an α of 0.05. All eligible adult patients undergoing renal transplantation at the Princess Alexandra Hospital will be offered participation in the trial. Exclusion criteria will include iron overload (transferrin saturation >50% or ferritin >800 μg/l), or previous intolerance of either oral or intravenous iron supplements.DiscussionIf the trial shows a reduction in the time to correction of anaemia with intravenous iron or less side effects than oral iron, then intravenous iron may become the standard of treatment in this patient group.

More Effective Route of Treatment for Iron Deficiency Anemia in Pregnancy Intravenous Vs Oral Iron