Depleted Iron Stores Research Articles

Therapeutic intervention with intravenous ferric carboxy-maltose: addressing iron deficiency among heart failure patients

Dear editor, Heart failure is a debilitating life sentence plagued with multifactorial variables that greatly influence the morbidity and mortality of the patient. Iron deficiency, one of these variables, is a leading contributor to anaemia among individuals with stable chronic heart failure, affecting approximately 30% to 50% of this population irrespective of left ventricular ejection fraction or demographic variables such as gender and race.(1,2) Intriguingly, even among those without overt anaemia, more than 40% display laboratory evidence of depleted iron stores. Moreover, in acute decompensated heart failure (HF), iron deficiency (ID) can be identified in as many as 80% of assessed patients, emphasizing the significance of research initiatives aimed at understanding the underlying cause of ID in HF patients and enhancing their clinical management.(3) A survey conducted in the region of South Asia revealed that 46% of Pakistani heart failure patients and 58.8% of those in India were affected by iron deficiency(4). Implementing simple practices to treat the underlying anaemia can massively improve the quality of life and reduce rehospitalization rates.(1–3,5) Notably, in Pakistan, the rehospitalization rate sits at a staggering 81%. Ferric carboxy-maltose is an intravenous iron formulation which has been extensively explored in clinical studies such as the IRON-CRT, IRONMAN and AFFIRM-AHF trials. The trials displayed promising outcomes with marked improvement in general well-being and physical capacities including 6-minute exercise tolerance as well as lowering the need for hospitalisation independent of baseline haemoglobin levels.(1,2,5) Ferric carboxy-maltose has demonstrated superiority over oral iron supplements and other treatments, such as erythropoietin stimulating medications, making it a recommended and successful alternative for iron deficiency therapy according to both European and American guidelines.(1–3,5) The latest heart failure guidelines emphasize the importance of screening for iron deficiency in every patient diagnosed with heart failure.(2) Unfortunately, the implementation of this practice is not consistently applied in developing countries, as observed in our own experiences in Pakistan. In conclusion, establishing Ferric Carboxy-maltose as the standard treatment for iron deficiency is recommended due to its cost-effective nature and the near instant improvement in patients health and morale. This approach would contribute to a more productive and fulfilling life for patients, even enabling them to regain some level of autonomy in their daily activities. ---Continue

Dietary diversity and iron deficiency anemia among a cohort of singleton pregnancies: a cross-sectional study

BackgroundIron deficiency anemia (IDA) is considered one of the most common medical disorders observed during pregnancy. In low- and middle-income countries (LMICs), anemia and micronutrients deficiencies among pregnant women are associated with low consumption of animal products, monotonous starchy-diets, and seasonal consumption of vegetables and fruits.MethodsA cross-sectional study was conducted with 198 pregnant mothers aged between 19–45 years who visited the antenatal care clinics in Northern Jordan to document the prevalence of IDA and to describe the associations between dietary diversity, diet quality scores and oral iron supplementation with the pregnant women iron status. Participants were stratified into three groups by gestational age (n = 66 women per group). Gestational age, blood parameters, minimum dietary diversity score (MDD-W), and prime diet quality score for healthy (PDQSHF) and unhealthy foods (PDQSUF) were assessed using 24- hour dietary recall.ResultsPrevalence of mild to moderate anemia was 27.8% among pregnant women. Third-trimester pregnant women were most affected. 52.5% have depleted iron stores (ferritin < 15 ng/ml), of them 30.8% have iron deficiency, and 21.7% have IDA. The (M ± SD) of the MDD-W, PDQSHF, and PDQSUF were 4.8 ± 1.6, 12.8 ± 3.9, and 7.2 ± 2.8 respectively. 52.5% achieved the MDD-W, 68% consumed < 4 servings/week of healthy food groups, and 50% consumed > 4 servings/week of unhealthy food groups. Mothers with higher MDD-W and PDQS had higher Hb and serum concentrations. Those taking iron supplements had significantly (p = 0.001) higher means of Hb, serum ferritin, and gestational weight gain. Significant differences were also found between PDQSHF, PDQSUF and the first and third trimester.ConclusionsMild to moderate IDA is prevalent among pregnant mothers, especially in the third trimester. However, the prevalence of IDA among Jordanian pregnant women is lower than the global average. A high-quality, diverse diet, combined with oral iron supplementation and food fortification with iron, will help improve iron status, prevent anemia, and reduce its prevalence.

Korelasi Pola Asupan Protein Dan Zat Besi Dengan Kadar Hemoglobin Pada Mahasiswi Prodi Kedokteran Universitas Khairun

Iron Deficiency Anemia (IDA) is anemia with the cause being a decrease in the amount of iron needed in the process of erythropoiesis due to depleted iron stores, causing a decrease in hemoglobin formation. Riskesdas data in 2018 stated that in 300,000 households, women experienced more anemia (27.2%) than men (20.3%). The anemia rate among 15-24 year olds reached 32% in 2018. Knowing the correlation of protein and iron intake patterns with hemoglobin levels in Khairun University Medical Study Program students. This research is an analytic study that uses a cross-sectional approach. The research sample was female students who met the inclusion criteria and were determined using purposive sampling technique. Data on protein and iron intake patterns were collected through interviews using the 24-hour food recall method taken twice. Data on hemoglobin levels were obtained from collection with a portable Hb meter. In 109 samples, the most common results were deficient protein intake (78.0%), deficient iron intake (75.2%), and normal hemoglobin (72.5%). and methodology are arranged in the form of past tense, while the results and conclusions in the form of simple present tense.

Nutritional status of flexitarians compared to vegans and omnivores - a cross-sectional pilot study

BackgroundIn the Western world, there has been a notable rise in the popularity of plant-based, meat-reduced flexitarian diets. Nevertheless, there is insufficient data on the nutritional status of individuals following this dietary pattern. The aim of this study was to investigate the intake and endogenous status of various nutrients in a healthy German adult study population consisting of flexitarians (FXs), vegans (Vs) and omnivores (OMNs).MethodsIn this cross-sectional study, dietary intake of 94 non-smoking adults (32 FXs, 33 Vs, 29 OMNs) between 25 and 45 years of age was assessed using 3-day dietary records. In addition, blood samples were collected to determine different endogenous nutrient status markers.Results32%, 82% and 24% of the FXs, Vs, and OMNs respectively reported using dietary supplements. In the FXs, intake of total energy as well as macronutrients and most micronutrients were within the reference range. FXs had higher intakes of fiber, retinol-equ., ascorbic acid, folate-equ., tocopherol-equ., calcium, and magnesium compared to OMNs. However, cobalamin intake in FXs (2.12 µg/d) was below the reference (4 µg/d). Based on 4cB12, 13% of FXs showed a cobalamin undersupply [< -0.5 to -2.5] compared to 10% of OMNs, and 9% of Vs. The median 25(OH)D serum concentrations in FXs, Vs and OMNs were 46.6, 55.6, and 59.6 nmol/L. The prevalence of an insufficient/deficient vitamin-D status [< 49.9 nmol 25(OH)D/L] was highest in FXs (53%), followed by Vs (34%) and OMNs (27%). In FXs and Vs, the supplement takers had better cobalamin and vitamin-D status than non-supplement takers. Anemia and depleted iron stores were found only occasionally in all groups. In women, the prevalence of pre-latent iron deficiency and iron deficiency was highest in FXs (67%) compared to Vs (61%) and OMNs (54%).ConclusionOur findings indicated that all three diets delivered sufficient amounts of most macro- and micronutrients. However, deficiencies in cobalamin, vitamin-D, and iron status were common across all diets. Further studies are needed to investigate the nutrient supply status and health consequences of meat-reduced plant-based diets. The study was registered in the German Clinical Trial Register (number: DRKS 00019887, data: 08.01.2020).

Direct Effect of Iron Deficiency Independent of Anemia on Adverse Perinatal Outcomes- a Scoping Review

Introduction Iron is required throughout pregnancy by both the pregnant individual and the fetus. Iron stores can be depleted during pregnancy resulting in iron deficiency (ID), which is the most common cause of anemia in pregnancy. Iron deficiency anemia (IDA) is associated with an approximately two-fold increase in adverse perinatal outcomes (APO) such as low birth weight (LBW), preterm delivery, and stillbirth. It is uncertain whether depleted iron store in a non-anemic pregnant individual affects fetal growth and well-being. The effect of ID per se on these outcomes, independent of anemia, is the central focus of this scoping review. If an independent association between iron deficiency without anemia (IDWA) and these APO is established and given the potential for non-anemic iron deficiency to progress to IDA, early screening, and intervention before the development of IDA may be important in preventing these morbidities and mortality. Our objective is to determine the current state of existing knowledge concerning IDWA and APO. The specific aims are to determine the prevalence of IDWA in pregnant individuals, assess predictors and determine types of APO associated with IDWA. Methods We performed a comprehensive systematic scoping review of the independent effect of IDWA on APO. The search for relevant studies involved Ovid Medline, Cochrane Database of Systematic Reviews, Cochrane Control Register of Controlled Trials, and hand search of citations of relevant articles for cohort and cross-sectional studies, randomized controlled trials, systematic reviews, and meta-analyses, scoping and narrative reviews from the inception of the databases. We used all relevant Medical Subject Headings terms and subheadings with no language restrictions. Two reviewers independently screened titles, abstracts, and full text based on the outlined inclusion and exclusion criteria. The inclusion criteria include relevant studies reporting on IDWA in pregnancy and APO. Exclusion criteria include studies not reporting IDWA and APO, and the presence of medical conditions such as hemoglobinopathies, polycythemia, iron overload, autoimmune and inflammatory conditions. Discrepancies were resolved through discussion and consensus. Covidence ® systematic review software was used for screening, automatically eliminating duplicates and data extraction. PRISMA for Scoping Reviews reporting guidelines was used. The selection process and results of included and excluded studies were presented with a PRISMA flow chart. A narrative summary was conducted to descriptively summarize the findings. Results A total of 4389 articles were identified from the searched databases after all duplicates were removed. Two studies conducted between 2005-2008 and 2017-2018 respectively met the inclusion criteria and were eligible for data extraction. A total of 5684 participants made up of 5479 Danish and 205 Spanish cohorts were included. The prevalence of IDWA in Denmark was 14.2% based on serum ferritin of &amp;lt;30μg/L and hemoglobin ≥110g/L and 20% in Spain using thresholds of SF &amp;lt;12μg/L and Hb≥110g/L. The mean (standard deviation, SD) age of participants was 31.8 ± 5.0 years in Denmark, and the mean (95% CI) was 31.0 (29.4-32.6) years in Spain. In the Danish study, the babies had a mean (SD) birth weight of 3508±523g and were on average 192g smaller (p=0.028). The mean (SD) gestational age (GA) at delivery was 39.8±1.7 weeks, adjusted odds ratio (95%CI) of LBW was 0.6 (0.4-1.0), stillbirth 4.0(1.0-14.3) and gestational diabetes mellitus 1.1 (0.7-1.7) in the IDWA group. The Spanish study reported a mean (95% CI) infant birth weight (IBW) of 3140 (3067-3213) g, reduction in adjusted IBW of -192.4 (-363.6, -21.2)g, p=0.028, R 2c.100 = 35.4, F 194,11 =9.3, p&amp;lt;0.001 in IDWA. Both studies reported the covariates and predictors of APO including parity, race, body mass index, and socioeconomic status. Conclusion Overall, there is limited research on this important obstetric hematology topic. The few available studies identified higher odds of non-causal association between IDWA, stillbirth, and smaller birth weight. Similarly, there was a non-significant causal association with most predictors and maternal medical complications of pregnancy. These findings will motivate further research work by our team. The study will involve the use of large population-based data to establish a potential causal association between IDWA and APO.

Serum Erythroferrone Levels in a Large General Population: Towards a Better Understanding of Connections between Erythropoiesis and Iron Homeostasis

Introduction: Iron is essential for various biological functions [ Ganz T., Physiol Rev 2013], especially for erythropoiesis which is the most iron-consumer process daily. Hepcidin is the key hormone of iron homeostasis, preventing both iron deficiency and excess, by modulating iron absorption, recycling, and mobilization [ Camaschella C. et al, Haematologica 2020]. Erythroferrone (ERFE) constitutes the principal erythroid regulator of hepcidin: in the presence of enhanced erythropoiesis, expanding erythroblasts produce ERFE which, by impeding bone morphogenetic proteins (BMPs) signaling in hepatocytes, suppress hepcidin, in turn increasing iron availability for the bone marrow [ Ganz T., Free Rad Biol Med 2019]. Increased ERFE levels have been demonstrated in expanded/ineffective erythropoiesis (IE) (e.g., in thalassemia intermedia), where chronic ERFE-mediated hepcidin suppression may cause progressive iron accumulation even in subjects not regularly transfused. In view of this, ERFE has been proposed as a potential biomarker of IE and an appealing target for treating iron overload deriving from IE [ Srole D.N. and Ganz T., J Cell Physiol 2020]. However, studies that fully elucidate the role of ERFE in the general population under physiological conditions are still lacking. Our project evaluated age- and sex-related variations in ERFE levels, and their correlations with hematological and iron status parameters, in a large subpopulation from the Cooperative Health Research In South Tyrol (CHRIS) study. Subjects and methods: The CHRIS study is a population-based study carried out in South Tyrol (Northern Italy) aimed at investigating acquired and genetic basis of common chronic conditions associated with aging [ Pattaro C. et al, J Transl Med 2015]. Blood samples were tested for several biochemical and molecular parameters, including those related to iron status, such as ferritin, transferrin saturation (TSat), soluble transferrin receptor (sTfR), hepcidin, and C282Y and H63D mutations. Serum ERFE was measured in stored aliquots by the Human Erythroferrone IETM ELISA kit (Intrinsic Lifesciences - The BioIron Company TM, USA), according to manufacturer instructions. Results: We measured ERFE in 3688 subjects aged &amp;gt;18 years (55% female). A total of 777 subjects (21% of the whole population; 57% females) had ERFE concentrations below the lower limit of detection for our method (we assigned them an arbitrary value of 0.16 for statistical analyses). Figure 1 illustrates age- and sex-dependent variations of ferritin, sTfR, hepcidin, and ERFE in the whole population. After stratification by hemoglobin (Hb) levels, we observed that ERFE was significantly higher in anemic (i.e., Hb&amp;lt;12 g/dl in females and &amp;lt;13 g/dl in males; n=100) than in non-anemic subjects (respectively 3.74 and 0.65 ng/ml; p&amp;lt;0.0001). In anemic subjects, ERFE showed a strong negative correlation with Hb (r = -0.5; p &amp;lt; 0.001), TSat (r = -0.58; p &amp;lt; 0.001), ferritin (r = -0.48; p &amp;lt; 0.001) and hepcidin (r = -0.32; p = 0.001), and a positive correlation with sTfR (r = 0.58; p &amp;lt; 0.001). Moreover, ERFE was higher in iron-deficient (ID) subjects (i.e., ferritin &amp;lt;30 mg/l; n=773) than in non-ID subjects (0.92 vs. 0.63 ng/ml; p&amp;lt;0.0001). Although ID subjects had lower Hb levels than non-ID subjects (13.7 vs 15 g/dl; p&amp;lt;0.0001), Hb levels were broadly within the normal range.To better explore the relationship between ERFE and iron status, we divided the population into 4 subgroups, according to sTfR and ERFE levels. Considering the skewed distribution of the variables, we used sTfR above or below the 3° tertile (1316 ng/ml), in order to identify subjects having higher or lower iron needs, respectively. Analogously, we further divided the population in subjects with ERFE above or below the 3° tertile (1.21 ng/ml). As illustrated in Figure 2, after stratification, we observed that hepcidin reduced, in subjects with high ERFE levels, when iron requirement was high (0.94 vs 2.10 nM; p &amp;lt; 0.0001), but it didn't when iron requirement was low (3.35 vs. 3.05 nM; p = 0.72), even in presence of normal Hb levels (Hb 14.3 g/dl). Discussion: our data confirmed an association among ERFE, Hb and iron status parameters under conditions of anemia (when erythropoiesis is stimulated); moreover, if confirmed in further studies, it could suggest an effect of ERFE on hepcidin regulation could be linked to depletion of iron stores, even before anemia develops.

Imbalance of iron needs and supply in patients with acute and chronic heart failure

Abstract Background Iron deficiency (ID) is frequent in patients with chronic and acute heart failure (CHF, AHF) associated with morbidity and mortality. ID can be absolute, defined as depleted iron stores (also named true ID), or functional describing hypoferremia despite adequate iron stores as a result of inflammation-related reduced iron mobilization and restriction in mononuclear cells. Empty iron stores can also be found simultaneously to inflammation-related reduced iron mobilization (combined ID). Purpose We aimed to better characterize ID and iron homeostasis in HF patients applying different biomarkers and to evaluate the accuracy of current ID definition by the ESC to indicate actual tissue iron needs and supply. Methods We performed a retrospective cohort study including 277 AHF and 476 CHF patients treated between 02/2021–05/2022 at the Medical University of Innsbruck. Results AHF patients had higher iron needs and lower iron supply than CHF patients, reflected by increased soluble transferrin receptor (sTfR) and sTfR-Ferritin (sTfR-F) index, and lower ferritin, serum iron, transferrin saturation (TfS), hepcidin and reticulocyte hemoglobin (Ret-Hb). Only 28.0% of CHF and 81.4% of AHF patients with absolute ID as well as 10.5% of CHF and 50.0% of AHF patients with combined ID based on the current ESC definition presented with an elevated sTfR-F index (&amp;gt;2.0 without and &amp;gt;3.2 with inflammation) and/or reduced Ret-Hb (&amp;lt;28pg), being indicative for tissue iron needs. Suppressed hepcidin expression (≤8.6ng/mL) as early marker of iron depletion was found in 80% of CHF and 91% of AHF patients with absolute ID and only in 19% of CHF and 32% of AHF patients with combined ID based on the current ESC definition. When breaking down the ID definition into ferritin and TfS, in AHF an elevated sTfR-F index was found in patients with inflammation and associated with lower ferritin (&amp;lt;200 ng/mL), while a reduced Ret-Hb was primarily found in patients with inflammation, TfS &amp;lt;20% and ferritin &amp;lt;100 ng/mL. In CHF an elevated sTfR-F index and a reduced Ret-Hb were primarily present in patients with ferritin &amp;lt;30 ng/mL and TfS &amp;lt;20% as well as in patients with inflammation, TfS &amp;lt;20% and ferritin &amp;lt;100 ng/mL. (Figure 1) Specificity for defining true ID based on iron needs was increased when including inflammation for defining true ID and reducing the upper limit of ferritin for defining true ID in the setting of inflammation (Figure 2). Conclusion A substantial proportion of patients with ID defined by the current ESC definition, had normal tissue iron supply with no increased tissue iron needs. In accordance with previous studies, results from our study suggest that the current ESC definition might overestimate true ID especially in CHF. A more accurate definition of ID may help to identify those patients with AHF and CHF who truly benefit from intravenous iron supplementation.

Long-Term Exposure to Cadmium Causes Hepatic Iron Deficiency through the Suppression of Iron-Transport-Related Gene Expression in the Proximal Duodenum.

Cadmium (Cd) is an environmental pollutant that damages various tissues. Cd may cause a depletion of iron stores and subsequently an iron deficiency state in the liver. However, the molecular mechanism of decreased iron accumulation in the liver induced by long-term exposure to Cd is unknown. In this study, we investigated the hepatic accumulation of iron and the proximal duodenal expression of the genes involved in iron transport using mice chronically exposed to Cd. Five-week-old female C57BL/6J mice were fed a diet containing 300 ppm Cd for 12, 15, 19 and 21 months. The iron concentration in the liver was markedly decreased by Cd. Among iron-transport-related genes in the proximal duodenum, the gene expression of HCP1 and Cybrd1 was significantly decreased by Cd. HCP1 is an influx transporter of heme iron. Cybrd1 is a reductase that allows non-heme iron to enter cells. The expression of iron-transport-related genes on the duodenal basolateral membrane side was hardly altered by Cd. These results suggest that long-term exposure to Cd suppresses the expression of HCP1 and Cybrd1 in the proximal duodenum, resulting in reduced iron absorption and iron accumulation in the liver.

Impact of iron supplementation on patient outcomes for women with abnormal uterine bleeding: a protocol for a systematic review and meta-analysis

BackgroundAbnormal uterine bleeding (AUB), which includes heavy menstrual bleeding (HMB), is a common condition placing women at increased risk for developing iron deficiency and iron deficiency anemia (IDA). Depletion of iron stores has negative implications on physical, social, and emotional health, as well as quality of life. Iron supplements are safe, effective, and readily available, while red blood cell (RBC) transfusions have inherent risks including infectious and immune reactions. Despite high prevalence of IDA among women with AUB, there are limited studies on the impact of iron therapies on patient outcomes. This systematic review and meta-analysis will evaluate the impact of iron supplementation on patient outcomes for women with AUB, when compared to combination therapy, no intervention, placebo, or standard of care.MethodsWe will conduct a systematic review and meta-analysis of randomized controlled trials and observational studies evaluating the impact of iron interventions on patient outcomes for women with AUB. Systematic literature searches will be conducted in major databases including MEDLINE, EMBASE, CENTRAL, CINAHL, and Web of Science. Studies assessing the impact of iron interventions on patient outcomes in women experiencing AUB, in comparison to combination therapy, no intervention, placebo, or standard of care, will be included in the review. Independent reviewers will screen for eligibility, assess risk of bias, and abstract data. Overall certainty of evidence for each outcome will be assessed using the GRADE approach. We will meta-analyze outcomes which are sufficiently homogeneous to summarize intervention effects and narratively synthesize nonhomogeneous outcomes. The main outcomes of interest are hemoglobin levels immediately prior to surgery and post-operatively, number of RBC transfusions, and adverse effects. Secondary outcomes will include length of hospital stay, intraoperative blood loss, adverse and side effects, quality of life, and iron indices.DiscussionThis review will evaluate the impact of iron interventions on patient outcomes in women with IDA secondary to AUB with focus on changes in hematological and iron indices, red blood cell utilization, quality of life, cost of treatment, and adverse events. The results will inform evidence-based clinical practice for the management of iron deficiency and IDA secondary to AUB.Systematic review registrationPROSPERO CRD42019137282.

Necessity of Implementing Ferritin Testing for Regular Blood Donors – A Cross-sectional Analysis of Serum Ferritin Levels in Individuals Donating Blood at Various Frequencies in a Year at a Regional Blood Transfusion Center

Background and Objectives: The virtuous act of blood donations should be encouraged and promoted by all means while safeguarding the well-being of the donor. If regular blood donations lead to iron store depletion in any individual, it may be identified and preventive measures should be taken. The current practice of hemoglobin (Hb) testing alone before donation may not detect the depletion of iron stores. Yet, a policy to introduce tests for iron stores and iron supplementation in regular donors requires extensive research in this area because of the cost and feasibility concerns. The objectives were to study the prevalence of subclinical anemia among voluntary blood donors using serum ferritin levels attending the blood transfusion center and to compare the average Hb and serum ferritin levels of donors across different age groups, gender, and donation frequencies. Methods: A cross-sectional study was done on 300 consecutively enrolled voluntary whole-blood donors (December 2018–November 2019) who fulfilled eligibility criteria. Donors were further divided into four groups, depending on their number of donations. Their samples were tested for Hb and serum ferritin to check for reduced body iron stores. The data obtained were analyzed using SPSS version 23. Results: A total of 300 regular voluntary donors were included in the study. 57.7% of donors were in the age group of 20–29 years, of which 83.33% were males. The total prevalence of subclinical anemia was 16%, in whom 54.2% were males and 45.8% were females. Out of the total female donors in our study (50), 44% suffered from subclinical anemia. Out of the total male donors in the study (250), 10.4% suffered from subclinical anemia. There was a significant association between frequency of donation and subclinical anemia (odds ratio [OR] =6.36, P &lt; 0.001). There was a significant association between subclinical anemia across gender (high for females; OR = 6.76, P &lt; 0.001). There was a significant correlation between the frequency of donation and serum ferritin (Spearman correlation coefficient: −0.299), but there was no correlation observed between the frequency of donation and Hb levels. Conclusion: The study demonstrates the depletion of iron store with increasing donation frequency. This calls for continual supervision of body iron stores rather than Hb alone to ensure the continuous supply of healthy blood donors.

Maternal Iron Status Is Dynamic Throughout Pregnancy and Might Predict Birth Outcomes in a Sex Dependent Manner: Results from the Alberta Pregnancy Outcomes and Nutrition (APrON) Cohort Study

BackgroundDevelopmental responses to nutrient deprivation may differ by fetal sex. Despite this, relationships between maternal prenatal iron biomarkers and birth outcomes when stratifying by offspring sex are poorly described, especially in healthy cohorts. ObjectivesThis study aimed to determine associations between maternal iron biomarkers and birth weights (BWs) and birth head circumferences (BHCs) among female and male newborns to assess whether the potential predictive ability of iron biomarkers on birth outcomes differs by offspring sex. MethodsThe Alberta Pregnancy Outcomes and Nutrition (APrON) cohort study recruited 2189 pregnant individuals from Calgary and Edmonton, Canada. Maternal blood was drawn at each trimester and 3 mo postpartum. Maternal serum ferritin (SF) concentrations were measured using chemiluminescent immunoassays and erythropoietin (EPO), hepcidin, and soluble transferrin receptor (sTfR) using enzyme-linked immunosorbent assays. Ratios of sTfR:SF and hepcidin:EPO were calculated and birth outcomes accessed through delivery records. Directed acyclic graphs informed multivariate regression models. ResultsThe risk of maternal iron deficiency increased throughout pregnancy because ∼61% showed depleted iron stores (SF < 15 μg/L) by the third trimester. Maternal hepcidin, SF, sTfR, and sTfR:SF concentrations changed across time (P < 0.01), and participants carrying female fetuses consistently (across 6 biomarkers) showed a lower iron status during the third trimester compared with those with male fetuses (P < 0.05). Higher maternal SF and hepcidin:EPO during the third trimester was associated with lower BWs in males (P = 0.006 for SF; P = 0.03 for hepcidin:EPO) and females (P = 0.02 for SF; P = 0.02 for hepcidin:EPO). There were additional inverse associations between BWs and third trimester maternal hepcidin (P = 0.03) and hemoglobin (P = 0.004) and between BHCs and maternal SF (second trimester; P < 0.05) and Hb (third trimester P = 0.02) but only in males. ConclusionsRelationships between maternal iron biomarkers and BWs and BHCs may depend on the timing of pregnancy and offpsring sex. There was a high risk of third trimester iron storage depletion among generally healthy pregnant individuals.

The impact of recommending iron supplements to women with depleted iron stores in early pregnancy on use of supplements, and factors associated with changes in iron status from early pregnancy to postpartum in a multi-ethnic population-based cohort

BackgroundWe aimed to evaluate the impact of recommending supplementation to pregnant women with serum ferritin (SF) < 20 µg/L in early pregnancy on use of supplements, and to explore which factors were associated with changes in iron status by different iron indicators to 14 weeks postpartum.MethodsA multi-ethnic population-based cohort study of 573 pregnant women examined at mean gestational week (GW) 15 (enrolment), at mean GW 28 and at the postpartum visit (mean 14 weeks after delivery). Women with SF < 20 µg/L at enrolment were recommended 30-50 mg iron supplementation and supplement use was assessed at all visits. Change of SF, soluble transferrin receptor and total body iron from enrolment to postpartum were calculated by subtracting the concentrations at the postpartum visit from that at enrolment. Linear and logistic regression analyses were performed to assess associations between use of supplements in GW 28 and changes in iron status and postpartum iron deficiency/anaemia. Change of iron status was categorized into ‘steady low’, ‘improvement’, ‘deterioration’, and ‘steady high’ based on SF status at enrolment and postpartum. Multinomial logistic regression analyses were performed to identify factors associated with change of iron status.ResultsAt enrolment, 44% had SF < 20 µg/L. Among these women (78% non-Western European origin), use of supplements increased from 25% (enrolment) to 65% (GW 28). Use of supplements in GW 28 was associated with improved iron levels by all three indicators (p < 0.05) and with haemoglobin concentration (p < 0.001) from enrolment to postpartum, and with lower odds of postpartum iron deficiency by SF and TBI (p < 0.05). Factors positively associated with ‘steady low’ were: use of supplements, postpartum haemorrhage, an unhealthy dietary pattern and South Asian ethnicity (p ≤ 0.01 for all); with ‘deterioration’: postpartum haemorrhage, an unhealthy dietary pattern, primiparity and no use of supplements (p < 0.01 for all), and with ‘improvement’: use of supplements, multiparity and South Asian ethnicity (p < 0.03 for all).ConclusionsBoth supplement use and iron status improved from enrolment to the postpartum visit among women recommended supplementation. Dietary pattern, use of supplements, ethnicity, parity and postpartum haemorrhage were identified as factors associated with change in iron status.

Analysis of Reticulocyte Hemoglobin Equivalent in Routine and Non-Routine Blood Donors in Makassar

Blood donation often causes the depletion of iron stores in the body resulting in anemia. One of the markers to assess the hemoglobin content in reticulocytes is Ret-He. This study aims to analyze Ret-He in routine and non-routine blood donors. This was a cross-sectional study using primary data from routine and non-routine blood donors at the Blood Transfusion Technical Implementation Unit of South Sulawesi Province from June 2021 to September 2021. The study population was blood donors who met the donor selection requirements. The research samples were blood donors who qualified as routine and non-routine blood donors. For a total of 66 blood donors, namely 33 routine blood donors and 33 non-routine blood donors, the mean Ret-He of routine blood donors (33.6 pg) was lower than that of non-routine blood donors (35 pg). The Mann-Whitney test showed a significant difference between routine and non-routine blood donors (p=0.008). Ret-He levels in routine blood donors were significantly lower than in non-routine blood donors. This is because routine blood donors donate blood more frequently and regularly, affecting the iron reserves in the donor's body. The study showed that the Ret-He level of routine blood donors was lower than that of non-routine blood donors but was still within the normal values of Ret-He (normal value: 30.2 pg - 36.7 pg). Ret-He levels in routine blood donors were lower than non-routine blood donors but were still within the normal range.

Vitamin E Induces Liver Iron Depletion and Alters Iron Regulation in Mice

BackgroundVitamin E (vit E) is an essential nutrient that functions as a lipophilic antioxidant and is used clinically to treat nonalcoholic fatty liver disease, where it suppresses oxidative damage and impedes the progression of steatosis and fibrosis. Mice lacking a critical liver iron–trafficking protein also manifest steatosis because of iron-mediated oxidative damage and are protected from liver disease by oral vit E supplements. ObjectivesWe aimed to examine the role of dietary vit E supplementation in modulating iron-sensing regulatory systems and nonheme iron levels in mouse liver. MethodsC57Bl/6 male mice, aged 6 wk, were fed purified diets containing normal amounts of iron and either control (45 mg/kg) or elevated (450 mg/kg) levels of 2R-α-tocopherol (vit E) for 18 d. Mouse plasma and liver were analyzed for nonheme iron, levels and activity of iron homeostatic proteins, and markers of oxidative stress. We compared means ± SD for iron and oxidative stress parameters between mice fed the control diet and those fed the vit E diet. ResultsThe Vit E–fed mice exhibited lower levels of liver nonheme iron (38% reduction, P < 0.0001) and ferritin (74% reduction, P < 0.01) than control-fed mice. The levels of liver mRNA for transferrin receptor 1 and divalent metal transporter 1 were reduced to 42% and 57% of the control, respectively. The mRNA levels for targets of nuclear factor erythroid 2–related factor (Nrf2), a major regulator of the oxidative stress response and iron-responsive genes, were also suppressed in vit E livers. Hepcidin, an iron regulatory hormone, levels were lower in the plasma (P < 0.05), and ferroportin (FPN), the iron exporter regulated by hepcidin, was expressed at higher levels in the liver (P < 0.05). ConclusionsOral vit E supplementation in mice can lead to depletion of liver iron stores by suppressing the iron- and redox-sensing transcription factor Nrf2, leading to enhanced iron efflux through liver FPN. Iron depletion may indirectly enhance the antioxidative effects of vit E.

Diagnostics of anemia and iron deficiency in patients with chronic heart failure

According to the recommendations of the European Society of Cardiology (ESC) 2021 for the management of patients with chronic heart failure (CHF), it is necessary to take into account the iron level in the diagnosis of all patients with firstly diagnosed heart failure (HF). Also the practical recommendations indicate that the assessment of iron deficiency is also carried out in patients with already confirmed CHF, especially if the symptoms of HF persist against the background of optimal treatment of the underlying disease, which necessitates knowledge of the diagnosis of anemia and iron deficiency in patients with CHF. The aim was review literature illustrating current data about diagnostics of iron deficiency and anemia in patients with CHF. In the work 28 sources from the Web of Science database and 7 sources from the PubMed database were analyzed. Anemia is diagnosed by hemoglobin levels. As criteria for iron deficiency, two parameters are used in clinical practice – ferritin level and transferrin saturation. The mean corpuscular volume of erythrocytes and the mean hemoglobin content in them were not reliable markers of iron deficiency and are not recommended for assessing iron deficiency in patients with HF. Depletion of iron stores in the bone marrow is a highly specific for iron deficiency, as it is not affected by inflammation and therefore the test for iron stores in the bone marrow is the gold standard for diagnosis, however its use in clinical practice is limited due to invasiveness and high cost. Diagnostic markers such as levels of hepsidin, dissolved transferrin receptor and ferritin index have low availability in laboratories. Since timely diagnosis followed by treatment of anemia and iron deficiency in patients with CHF impoves the quality of life of patients, therefore, increasing the diagnostic value of tests to identify iron deficiency remains a question for active research.

Iron Deficiency Anemia in Colorectal Cancer Patients: Is Preoperative Intravenous Iron Infusion Indicated? A Narrative Review of the Literature.

Iron deficiency anemia is the most common extraintestinal symptom in patients with colorectal cancer (CRC). Inflammation associated with malignancy leads to functional iron deficiency via the hepcidin pathway, whereas chronic blood loss causes absolute iron deficiency and depletion of iron stores. The assessment and treatment of preoperative anemia is of great importance in patients with CRC, since published data have consistently shown that preoperative anemia is associated with increased need for perioperative blood transfusions and more postoperative complications. Recent studies have documented mixed results regarding the preoperative intravenous iron administration in anemic CRC patients in terms of efficacy for anemia correction, cost-effectiveness, need for transfusions and risk for postoperative complications.

Iron Deficiency Anemia among Alaska Natives May Be Due to Fecal Loss Rather than Inadequate Intake

To define more fully the nature of a persistently high prevalence of iron deficiency anemia observed among Alaska Native children, we examined dietary iron intake, hemoglobin concentrations, and storage iron (serum ferritin) based on multiple cross-sectional surveys of Alaska Natives between 1983 and 1989. Approximately 30 to 50% of the children studied <12 y of age had depleted iron stores. Anemia and depleted iron stores also were prevalent among adult men and women, about twice as prevalent as in the U.S. population based on the Second National Health and Nutrition Examination Survey (NHANES II). The higher rate of iron deficiency, occurring even when the dietary assessment found Alaska Native iron intake to be higher than the U.S. average with an ample intake of food high in bioavailable iron, suggests blood loss as a possible cause of the unusual pattern of iron deficiency observed. In a pilot study of stool blood loss in two villages, 65% of the samples had a significantly elevated stool heme concentration. Further investigation of iron deficiency due to gastrointestinal blood loss for the Alaska Native is warranted.

Effect of maternal haemoglobin, serum ferritin and gestational age on neonatal iron indices

Background: Iron is the most common micronutrient deficiency in pregnant women and infants throughout the world, mainly in developing countries like India. 30 to 50% of the pregnancies are affected by maternal iron deficiency and in developing countries, more than 80% of the pregnant women are estimated to be anemic. The effects of perinatal iron deficiency are anemia and most importantly neurodevelopmental impairments which are long-lasting and sometimes irreversible. The main goal of this study was to determine the influence of maternal and neonatal factors on the iron stores in neonates and to estimate the appropriate time to supplement iron for neonates in different scenarios. Methods: This is a prospective observational study. Mother-infant pairs were enrolled in the study by following specific inclusion and exclusion criteria. Maternal demographic details, complications during pregnancy, intrapartum details, and neonatal details were recorded. The maternal and cord blood samples were collected for measurement of hemoglobin, serum ferritin, serum iron, total iron-binding capacity, and transferrin saturation. If failed to collect the cord blood sample, the first 24hour sample of the baby was taken into consideration in place of it. The correlation between maternal neonatal iron indices and the influence of the gestational age and IUGR on cord serum ferritin levels was analyzed by using paired t-test and chi-square test for multiple groups. A probability of p&lt;0.05 (two-sided) was used to consider the difference as significant. Results: 125 term and 47 preterm neonates were included in the study. There was correlation between maternal and neonatal iron profiles at birth when there was severe depletion of maternal ferritin (&lt;12µg/dl) with p values less than 0.05 for hemoglobin and serum ferritn levels. Serum ferritin levels at birth were less in preterm as compared to term neonates (mean of 128.9µg/l in the preterm vs. 156.9µg/l in the term, p=0.04). There was a significant correlation between neonatal iron indices at birth with that at 28 days of life (p&lt;0.01). Conclusions: Neonatal iron stores are not affected unless there was severe depletion of maternal iron stores. Preterm neonates have low iron stores compared to term neonates. Gestational age is the major determinant for iron stores at birth as compared to other maternal and neonatal factors. As the most significant adverse effects of iron deficiency are irreversible and long-lasting neurodevelopmental impairments. The term and preterm babies should take prophylactic iron from eight weeks and four weeks of age respectively and continued up to the introduction of iron-fortified cereals as recommended by the American academy of paediatrics.

Assessment of iron status and iron deficiency anemia in patients with celiac, a single center experience.

This study aimed to assess the status of iron stores and the frequency of iron deficiency anemia in Celiac disease (CD) patients referred to the Golestan Research Center of Gastroenterology and Hepatology, Gorgan, Iran. Studies have shown that nutritional deficiencies affect 20-38% of patients with CD due to malabsorption and as a result of a gluten-free diet. In this study, 59 out of 100 CD patients were assessed. The presence and severity of anemia were determined using the concentration of serum hemoglobin according to WHO criteria. The status of body iron stores was also assessed based on serum ferritin levels. Mean and SD of age, duration of disease, serum hemoglobin, ferritin, TIBC, and serum iron were 39.9±11.9 years, 69.8±45.4 months, 12.6±1.99 g/dl, 54.3±55.3 mg/dL, 365.9±49.1 μg/dL, and 84.1±37.1 μg/dL, respectively. 68.42% had no anemia, 19.3% had mild anemia, 8.77% had moderate anemia, and 3.51% had severe anemia. 25.42% of patients had depleted iron stores, 71.19% had normal iron stores, and 3.39% were exposed to iron overload. There was a statistically significant correlation between serum hemoglobin and the duration of disease diagnosis (P=0.037, r=0.302). In this study, 31.58% of CD patients on a gluten-free diet had some degree of anemia. In addition, 25.42% of patients had depleted iron stores. These results suggest that CD patients should be evaluated for iron status, even with a gluten-free diet.

A Retrospective Study of Various Iron Preparations Oral Administration in Pregnant Women with Iron Deficiency Anemia.

During pregnancy anemia is a common medical condition, with iron deficiency and megaloblastic anemia being the most common. The symptoms range from very mild to severe and if left without proper medical treatment, there can be serious consequences for both mother and fetus. The most frequent pregnancy problem is anemia. The term "Iron Deficiency Anemia" refers to erythropoiesis under conditions of absolute iron deficiency. This presupposes the depletion of iron stores in the body. Iron deficiency anemia or Sideropenic anemia is the most common form of anemia worldwide. Special attention must be given to nutrition during pregnancy. In the current retrospective study, it was evaluated the contribution of various iron preparations substitution during the pregnancy and puerperium.