Iron supplementation during malaria infection in pregnancy and childhood:A review

Malaria presents a significant global public health challenge,with severe malarial anaemia being a primary manifestation of the disease.The understanding of anaemia caused by malaria remains incomplete,making the treatment more complex.Iron is a crucial micronutrient essential for haemoglobin synthesis,oxygen delivery,and other vital metabolic functions in the body.It is indispensable for the growth of human beings,as well as bacteria,protozoa,and viruses in vitro and in vivo.Iron deficiency is among the most common nutritional deficiencies and can have detrimental effects during developmental stages of life.Malaria-induced iron deficiency occurs due to the hemolysis of erythrocytes and the suppression of erythropoiesis,leading to anaemia.Meeting iron requirements is particularly critical during pivotal life stages such as pregnancy,infancy,and childhood.Dietary intake alone may not suffice to meet adequate iron requirements,thus highlighting the vital role of iron supplementation.While iron supplementation can alleviate iron deficiency,it can exacerbate malaria infection by providing additional iron for the parasites.However,in the context of pregnancy and childhood,iron supplementation combined with malaria prevention and treatment has been shown to be beneficial in improving birth outcomes and ensuring proper growth and development,respectively.This review aims to identify the role and impact of iron supplementation in malaria infection during the life stages of pregnancy and childhood.

Single vs. Double Dose Iron Supplementation for Prevention of Iron Deficiency Anemia in Twin Pregnancy: A Randomized Controlled Clinical Trial

Introduction: It is estimated that about 18% of pregnant women suffer from iron deficiency anemia throughout their whole pregnancy. In twin pregnancy, owing to the relatively greater feto-placental requirements and greater expansion in maternal plasma volume and red cell mass, iron requirements are magnified 1.8 times compared to singleton pregnancies. However, for prevention of iron deficiency in twin pregnancy, only sparse data exist regarding the sufficiency of the standard antenatal iron supplementation dose used in singleton pregnancies to meet the increased iron demand. In this study, we investigate the effect of single and double dose iron supplementation for prevention of iron deficiency anemia in twin pregnancy. Methods: A randomized controlled clinical trial was conducted at our center in the period between February 2019 and October 2020, and included 450 eligible healthy non-anemic women aged 18 - 35 years, with twin pregnancy at 12 - 16 weeks of gestation. After informed consent, eligible women were randomized to receive either single dose 27 mg, or double dose 54 mg elemental iron supplementation. Monitoring of hemoglobin concentration was done at fixed time points during gestation: at enrollment, 24 weeks, 32 weeks and before delivery. The primary outcome of the study was the incidence of iron deficiency anemia during follow up until delivery. Results: The incidence of iron deficiency anemia in the two groups did not differ significantly between the single dose group (19.1%) and the double dose group (24.0%). In women who did not develop Iron Deficiency Anemia, hemoglobin concentration varied significantly along the different gestational ages during the follow up period. In contrast, they did not show an overall statistically significant difference in the hemoglobin concentrations between the single or double dose groups. Conclusion: This clinical trial did not demonstrate an added benefit for doubling prophylactic iron supplementation dose in non-anemic women with twin pregnancy.

Iron supplementation for non-anaemic pregnant women and the incidence of hypertensive disorders in pregnancy:A systematic review and meta-analysis

Objective:To investigate effect of iron supplementation on the risk of hypertensive disorders in pregnancy in non-anaemic pregnant women.Methods:A literature search was conducted using three categories of terms with its synonyms or related words:"iron","supplement",“hypertensive disorders in pregnancy”through MEDLINE(OVID),CINAHL,PubMed,Cochrane Library,Scopus,Web of Science,ICTRP,and ClinicalTrials.gov,and manual search of references was used in seven potential resources.The inclusion criteria were randomized control trials(RCTs),published in English,full-text available,having healthy pregnant women without anaemia for study participants,and having hypertensive disorders in pregnancy at the end of pregnancy as the outcome.The risk of bias assessment tool was used for quality appraisal.Meta-analysis was conducted by calculating the fixed and random effects of the odds ratio(OR)for iron supplementation among non-anaemic pregnant women compared with the incidence of hypertensive disorders in pregnancy.The range of the study’s estimation accuracy was reflected by a 95%confidence interval(CI).Results:Four RCTs were included in the meta-analysis.The pooled results showed that iron supplementation possibly had no effect on the incidence of hypertensive disorders in pregnancy(OR 0.93,95%CI 0.81-1.07;P=0.30),gestational hypertension(OR 1.37,95%CI 0.69-2.73;P=0.36)as well as on the development of preeclampsia(OR 1.45,95%CI 0.71-2.97;P=0.31).Conclusions:Iron supplementation has no effect on the incidence of hypertension in non-anaemic pregnant women.In general,there is a lack of evidence for the association between iron supplementation and the incidence of hypertensive disorders in pregnancy among non-anaemic pregnant women,and further studies are needed.

Benefit of Iron Supplementation with Ferric Sodium EDTA (NaFe ³⁺-EDTA) in the Treatment of Anemia during Pregnancy in Democratic Republic of Congo (FERARI Study)

Background: Oral iron supplements, usually in the form of ferrous salts, are associated with gastric side effects, poor compliance and failure of anemia treatment. To make iron more bioavailable, reduce the gastric side effects and increase the patient compliance, newer iron form, Ferric Sodium EDTA, has become available on the market. Objective: To assess the change in hemoglobin level after iron supplementation with Ferric Sodium EDTA during pregnancy. Materials and Methods: This is a longitudinal study concerning 337 women attending antenatal care in maternity hospitals in the Democratic Republic of Congo from May to December 2020. The study included sociodemographic and anthropometric variables along with type of feed, hemoglobin level at recruitment and after three weeks of taking iron supplement with Ferric Sodium EDTA (Hemoforce Plus Zinc® syrup). For statistical analysis, we used t-test or ANOVA and chi-square test, the significance being stated at p < 0.05. Results: The frequency of pregnancy anemia was 51.4%. The mean hemoglobin value of the overall study group was 8.7 ± 0.5 g/dL. The mean maternal age and weight were 28.9 ± 6.2 years and 65.3 ± 11.7 kg, respectively. Most pregnant women (83.1%) had a diet consisting of food of plant and animal origin in equal proportions. Mean of Body Mass Index (BMI) was 24.6 ± 4.6 Kg/m2 and 44.3% were overweight and obese. The co-morbidities associated were malaria and intestinal parasitosis found in 45% and 5.9% of cases, respectively. After iron treatment with Ferric Sodium EDTA, the average hemoglobin level increased to 11.2 g/dL with mean gain of 2.5 g/dL (p < 0.001). Pregnant women with excess weight (≥90 kg) and malaria as a comorbidity achieved a significantly lower mean hemoglobin gain (p = 0.014 and p = 0.022, respectively). Majority of women (91.2%) had not experienced the metallic taste of the syrup. Conclusion: Ferric Sodium EDTA as a novel iron formulation (Hemoforce Plus Zinc®) has shown a rapid increase in hemoglobin levels in pregnant women suffering from anemia. The speedy rise in hemoglobin is related to the property of Ferric Sodium EDTA to enhance the iron absorption by inhibiting the dietary iron inhibitors. Thus, Ferric Sodium EDTA should be used as an effective and promising iron supplement in pregnant women with iron deficiency anemia.

Effect and Safety of Iron Supplementation on Mild Thalassemia Complicated by Iron Deficiency in Late Pregnancy

Aim:To study the clinical effect and safety of iron supplementation in the treatment of mild thalassemia complicated by iron deficiency in late pregnancy.Methods:376 patients with mild thalassemia complicated by iron deficiency in late pregnancy treated in our hospital from July 2019 to June 2021 were selected and recruited in the research group,and 200 normal pregnant women treated in the same period were selected and recruited in the control group.Hemoglobin(Hb),reticulocyte blood,red blood protein(RET he)level,ferritin(SF)level,soluble transferrin receptor(sTfR)level,adverse maternal and infant outcomes,etc.were analyzed.Results:There was no significant difference in the levels of SF,Hb,RET he and sTfR between the two groups before treatment.After treatment,the levels of SF,Hb,RET he and sTfR in the research group were significantly improved,which was statistically significant compared with the control group.The frequencies of intrapartum hemorrhage,premature delivery,stillbirth,hemorrhagic shock,and neonatal asphyxia in the research group were 289±47.88,36(9.57%),0(0.00%),25(6.65%),and 6(1.26%),respectively.The frequencies of intrapartum hemorrhage,premature delivery,stillbirth,hemorrhagic shock,and neonatal asphyxia in the control group were 284±46.99,7(3.50%),0(0.00%),6(3.00%),and 0(0.00%),respectively.There were significant differences in preterm delivery and hemorrhagic shock,and there was no significant difference in other delivery outcomes.Conclusions:Under the premise of strictly controlling the iron reserve in pregnant women,continuous medication until the end of delivery may be conducive to the control of maternal thalassemia complicated by iron deficiency and the improvement of pregnancy outcome.

Iron-Deficiency Anemia Management in Gynecological Surgery: A Review of Current Evidence and Best Practices

Purpose: Due to the high prevalence of iron deficiency anemia in women undergoing gynecological surgeries and its association with worse postoperative results, it is necessary to identify and treat anemia preoperatively. However, although anemia and iron deficiency are significant global health problems, there are still disparities in the recognition and implementation of “Patient Blood Management” (PBM) as a comprehensive approach to mitigating the risks associated with these diseases. The purpose of the study is to review best practices for the treatment of anemia based on the Enhanced Recovery After Surgery (ERAS) protocol and PBM recommendations. Methods: This study reviewed the literature on preoperative iron deficiency anemia in patients undergoing gynecological surgery. We identified references through searches in PubMed using relevant search terms. Results: Among the various strategies used in PBM, perhaps the most important is the early detection and management of anemia. In gynecological surgery, there are several approaches to reducing perioperative blood loss, highlighting the use of gonadotropin-releasing hormone (GnRH) agonists (aGnRh) and antifibrinolytics. Oral and intravenous iron supplementation can be performed in addition to blood transfusion to treat anemia. Conclusion: Addressing preoperative and postoperative anemia through systematic correction, following the guidelines of the ERAS protocol and PBM guidelines, is essential to improving perioperative outcomes in women undergoing gynecological surgery.

Adherence to iron and folic acid supplementation and associated factors amongmothers receiving antenatal care in Lira district, Uganda

Background:Prenatal iron and folic acid supplementation is an economical strategy for reducing iron and folic acid deficiency anemia among expectant mothers in resource-limited countries like Uganda.This study aimed to assess the level of compliance with iron and folic acid supplementation(IFAS)and identify associated factors among mothers receiving prenatal services in Lira district,Uganda.Methods:A cross-sectional study was conducted at the antenatal clinic of Lira Regional Referral Hospital,involving 252 pregnant mothers.Adherence levels to IFAS were evaluated using a visual analogue scale,and associated factors were collected through an interviewer-administered questionnaire.The data were analyzed using SPSS software,and the results were presented in tables.Results:Only 46%of the mothers attending the antenatal clinic adhered to IFAS during the 30 days preceding the study.Participants who had good knowledge of IFAS before recruitment(odds ratio(OR)1.49,95%confidence interval(CI)1.12–1.97),utilized reminder techniques(OR 1.05,95%CI 1.02–1.09),and received support from their partners or relatives(OR 1.56,95%CI 1.07–2.29)were more likely to have good adherence.The main reasons for missing IFAS were forgetfulness and fear of taking too many tablets.Conclusions:There was a low adherence rate to IFAS among mothers attending antenatal clinics in Lira district.Further investigations are recommended to identify barriers to adherence,and comprehensive health education programs should be provided to pregnant mothers.

TREATMENT OF IRON DEFICIENCY ANEMIA IN CHILDREN BY IRONSUPPLEMENTATION TWICE WEEKLY AND WEEKLY

Objective The effect of intermittent iron supplementation weekly and twice weekly was studied in children with iron deficiency anemia(IDA). Methods Subjects were 58 children who were randomly divided into two groups. One group received a dosage of 2mg/kg Fe every 3d for 9 weeks. The other group received the same dose Fe once a week for 12 weeks. Results Hemoglobin and serum ferrltin increased significantly after treatment in both groups (P <o.o5), and zinc protoporphyrin decreased significantly (P <o. o5). But serum rerrltin of both groups was different after 6 weeks of treatment (P<o. o1). The side effect of the group supplemented once every 3d was higher than that of the group once a week, but there was no statistically significant difference. Conclusion Iron supplementation every 3d has a similar effect to once a week for treatment of IDA. The former should be used for the serious patients for 6 weeks. The later should be used for infants and the patients whose resistance of intestines and stomach are not good.

Flammulina velutipes polysaccharide-iron (Ⅲ) complex used to treat iron deficiency anemia after being absorbed via GLUT2 and SGLT1 transporters

Iron deficiency anemia(IDA)is a common nutritional problem, but traditional iron supplements cause many adverse reactions. Thus, the development of a novel iron supplement might be significant for the treatment of IDA. This study aimed to study the transport mechanism of Flammulina velutipes polysaccharide-iron complex(FVP1-Fe(Ⅲ))in Caco-2 cells and the therapeutic effect on IDA rats, as well as the influence on gut microbiota in vivo. These results showed that in vitro, the uptake of FVP1-Fe(Ⅲ)was mediated by sodium-dependent glucose transporter-1(SGLT1)and facilitated glucose transporter-2(GLUT2)and GLUT2 played a dominant function. The multidrug resistance-associated protein-2(MRP-2)was involved in the efflux of FVP1-Fe(Ⅲ)across the Caco-2 cells. In vivo, FVP1-Fe(Ⅲ)had a better restorative effect on blood parameters and iron status indicators in rats with IDA as compared with FeSO_4 and exerted this effect by downregulating the expression of hepcidin. FVP1-Fe(Ⅲ)could also regulate gut microbiota dysbiosis in iron deficiency rats by returning the relative abundance of gut microbiota to the normal level. Besides, as a dietary factor, vitamin C(vit C)could enhance the therapeutic effect of FVP1-Fe(Ⅲ). These present findings showed that FVP1-Fe(Ⅲ)could be exploited as a novel iron supplement to treat IDA.

The Effects of High Energy and Micronutrient Supplementation on Iron Status in Nutritionally at Risk Infants

The study assessed the effects of supplementary feeding over 180 consecutive days on iron status of infants and toddlers at six tea plantation in West Java, Indonesia. The design used was a clinical trial: two eohorts (i.e., 12 and 18 months old children) and three treatment groups (i.e., energy + micronutrient, micronutrient alone, and placebo) per cohort. Every day except Sunday, the infants attended day-care centers. Twenty four centers and 136 infants were selected. The infants were screened for weight and length and those meeting the criteria (i.e., <-1 SD of length-for-age, and between -1 and -2 SD of weight-for-length of the NCHS reference) were included. The experimental unit was the day-care centers (DCC), where each DCC was randomly assigned to one of the three treatment. As expected, groups of energy + micronutrient and micronutrient alone of the 12 months cohort experienced a significant upward shift in hemoglobin, ferritin and TS and a downward change in FEP, while the values for the group of placebo remain about the same as at base line. In the first 6 month of treatments, the ANOVA for each iron indicator yielded significant main effects of treatment (P<0.01) and for Hb with (P =0.059) on 12 months cohort. On the other hand, the main effects of treatment on hemoglobin, TS, ferritin and FEP were not significant for the 18 months cohort. In the second 6 month of treatments, the only significant of the treatment effect (P<0.01) was in serum ferritin on 18-month cohort. Under these circumstances, energy has a positive role in improving iron stores. It is likely that the equilibrium of hemoglobin and each iron indicators were reached in 6 months of treatment except ferritin still continued to increase up to 12 month. The effects of treatment on the improvement of iron status was stronger in 12 months than in 18 months

Effect of Vitamin C Supplementations on Iron Deficiency Anemia in Chinese Children

A total of 65 children with mild iron deficiency anemia (IDA) were divided into 5 groups, and received 0, 25, 50, 100 and 150 mg/day of vitamin C (VC) respectively every day for 8 weeks. Hemoglobin, serum ferritin, free erythrocyte and hematocrit were determined every week. At a daily average intake of about 30 mg of VC and 7.5 mg of Fe, the results of the study indicate that: (1) VC supplement alone could effectively control children's IDA, and a dose-dependant relationship was observed. (2) 50 mg/day of VC is the most efficient dosage and 6 weeks is the shortest time for an effective therapy. (3) With a diet predominately comprised of plant foods, it is suggested that appropriate dose of VC should be supplemented for the children during winter and spring in northeastern areas of China.

Juvenile ferric iron prevents microbiota dysbiosis and colitis in adult rodents

AIM: To assess whether juvenile chronic ferric iron ingestion limit colitis and dysbiosis at adulthood in rats and mice. METHODS: Two sets of experiments were designed. In the first set, recently weaned mice were either orally administered ferrous (Fe2+) iron salt or ferric (Fe3+) microencapsulated iron for 6 wk. The last week of experiments trinitrobenzene sulfonic acid (TNBS) colitis was induced. In the second set, juvenile rats received the microencapsulated ferric iron for 6 wk and were also submitted to TNBS colitis during the last week of experiments. In both sets of experiments, animals were sacrificed 7 d after TNBS instillation. Severity of the inflammation was assessed by scoring macroscopic lesions and quantifying colonic myeloperoxidase (MPO) activity. Alteration of the microflora profile was estimated usingquantitative polymerase chain reaction (qPCR) by measuring the evolution of total caecal microflora, Bacteroidetes, Firmicutes and enterobacteria. RESULTS: Neither ferrous nor ferric iron daily exposures at the juvenile period result in any effect in control animals at adulthood although ferrous iron repeated administration in infancy limited weight gain. Ferrous iron was unable to limit the experimental colitis (1.71 ± 0.27 MPO U/mg proteinvs 2.47 ± 0.22 MPO U/mg protein in colitic mice). In contrast, ferric iron significantly prevented the increase of MPO activity (1.64 ± 0.14 MPO U/mg protein) in TNBS-induced colitis. Moreover, this positive effect was observed at both the doses of ferric iron used (75 and 150 mg/kg per day po - 6 wk). In the study we also compared, in both rats and mice, the consequences of chronic repeated low level exposure to ferric iron (75 mg/kg per day po - 6 wk) on TNBS-induced colitis and its related dysbiosis. We confirmed that ferric iron limited the TNBS-induced increase of MPO activity in both the rodent species. Furthermore, we assessed the ferric iron incidence on TNBS-induced intestinal microbiota dysbiosis. At first, we needed to optimize the isolation and quantify DNA copy numbers using standard curves to perform by qPCR this interspecies comparison. Using this approach, we determined that total microflora was similar in control rats and mice and was mainly composed of Firmicutes and Bacteroidetes at a ratio of 10/1. Ferric juvenile administration did not modify the microflora profile in control animals. Total microflora numbers remained unchanged whichever experimental conditions studied. Following TNBS-induced colitis, the Firmicutes/Bacteroidetes ratio was altered resulting in a decrease of the Firmicutes numbers and an increase of the Bacteroidetes numbers typical of a gut inflammatory reaction. In parallel, the subdominant population, the enterobacteria was also increased. However, ferric iron supplementation for the juvenile period prevented the increase of Bacteroidetes and of enterobacteria numbers consecutive to the colitis in both the studied species at adulthood.CONCLUSION: Rats and mice juvenile chronic ferric iron ingestion prevents colitis and dysbiosis at adulthood as assessed by the first interspecies comparison.

Optimization of Chelation Process for Complex Microelement Iron Supplement Derived from Pig Blood by Response Surface Methodology

[Objectives]This study aimed to optimize the chelation process for complex microelement iron supplement derived from pig blood by response surface methodology.[Methods]On the basis of single-factor test,p H value,concentration of polypeptide solution and volume ratio of polypeptide solution to FeCl_2 solution were selected as influencing factors with Fe(II)chelation rate as the indicator for Box-Behnken central composite experimental design with three factors and three levels.The effects of three factors on the response value were analyzed by response surface methodology.[Results]The optimized chelation process for complex microelement iron supplement derived from pig blood by response surface methodology was as follows:pH 5.40,polypeptide solution concentration 2.27%,volume ratio of polypeptide solution to FeCl_2 solution 2.16∶1.Under this condition,the predictive Fe(II)chelation rate of iron supplement was 79.37%,while the actual value was 79.41%.[Conclusions]The optimized process may provide new thoughts for the development and utilization of complex microelement iron supplement derived from pig blood.

Effect of Sheng Xue Ning Tablets on Renal Anemia in Patients Subject to Maintenance Hemodialysis and Safety Evaluation: A Multi-setting Prospective Randomized Study

This study compared Sheng Xue Ning(SXN)tablets with ferrous succinate(FS)tablets in terms of their efficacy for the treatment of iron-deficient renal anemia and safety in patients subject to maintenance hemodialysis(MHD).A total of 94 patients undergoing MHD were randomly assigned to an experiment group(receiving oral SXN tablcts,SXN group)and a control group(orally given FS tablets,FS group)and followed up for 12 weeks.Erythropoietin(EPO)was used in both groups.The eficacy was assessed by detecting the subsequent changes in hemoglobin(Hb),serum iron(SI),SF and transferrin saturation(TSAT).At the 12th week,Hb and TSAT levels in both groups were significantly increased compared to those in the screening period(P<0.05).However,no significant difference in Hb and TSAT was found between the two groups.The average weekly EPO dosage used was lower in SXN group than in FS group(P<0.05)at the 10th week and the 12th week.Our study showed that SXN tablets can effectively ameliorate renal anemia and keep iron metabolism stable in MHD patients,and its efficacy is virtually close to that of FS tablets.Meanwhile,SXN tablets can reduce the dosage of EPO and have a good safety profile.