Parenteral Iron Administration Research Articles

Cardiac Arrest During a Ferric Derisomaltose Infusion Followed by Complete Heart Block: A Case Report.

Ferric derisomaltose is the newest available parenteral iron formulation. Studies have demonstrated a good safety profile with improved tolerability compared to alternative parenteral iron formulations. To date there have been no reported acute, life-threatening cardiac events associated with ferric derisomaltose. An 86-year-old male who had previously tolerated routine iron infusions received a first dose of ferric derisomaltose at an outpatient infusion clinic. Six minutes into the infusion the patient became unresponsive with no palpable pulse. Return of spontaneous circulation was achieved after two minutes of chest compressions. Electrocardiogram showed complete heart block requiring transcutaneous pacing and vasopressor administration. The patient was transferred to the emergency department for stabilization and then admitted to the cardiac intensive care unit. During admission, the patient received a dual-chamber, permanent pacemaker without complication and was ultimately discharged. It may be reasonable to consider parenteral iron as a toxicological etiology for patients presenting with complete heart block temporally associated with parenteral iron administration, particularly in patients with underlying conduction abnormalities.

Management of Childhood Iron Deficiency Anemia in a Developed Country-A Multi-Center Experience from Croatia.

Iron deficiency anemia (IDA) continues to be a global public health concern, mostly in the developing countries. However, precise epidemiological data on childhood IDA in Croatia are lacking. In order to establish its frequency, underlying etiologies, the rationale for tertiary care visits, diagnostic practices, and current treatment regimens of IDA, medical records of children referred to pediatric hematologists for iron deficiency in a five-year period at tertiary institutions (Zagreb, Rijeka, Split, Osijek) throughout Croatia were retrospectively analyzed. Eight hundred and sixty-four children, predominately of preschool age, were referred mainly by the primary care pediatricians, who, in general, performed basic diagnostics but failed to initiate oral iron therapy in half of the patients. Approximately one-third of patients were symptomatic, with inadequate nutrition prevailing as underlying etiology. Dextriferron was the preferred iron formulation among hematologists, with a median dose of 5 mg/kg, with acceptable compliance rates (63.5-93.2%). Hospital admission rates varied among the centers (9.4-35%), and so did transfusion policies (6.4-22.9%). The greatest difference was observed in the frequency of parenteral iron administration (0.3-21.5%). In conclusion, the burden of childhood IDA, even in a high-income country, remains substantial, necessitating consistent implementation of national guidelines and additional education of primary health care providers.

Iron-Overload Conditions: Manifestations to the Kidney Organs – A Review

Excess iron is a risk factor for organ dysfunction and damage resulting in various organ diseases such as liver, heart, and kidney, diabetes mellitus, and neurodegenerative diseases. Iron overload in some individuals is caused by various factors, including genetic predisposition such as genetic hemochromatosis, repeated transfusion of red blood cells, and parenteral iron administration in conditions of transfusion-dependent anemia. A disturbance in the globin gene in diseases such as β-thalassemia major causes an imbalance of the globin chain, resulting in chronic anemia in the sufferer. It has been reported that the human body does not have a mechanism for eliminating excess iron levels. Routine transfusion has become a solution to overcome chronic anemia so that patients can maintain hemoglobin levels, and the result of this transfusion repetition is the accumulation of iron in various organs, such as the heart, liver, endocrine glands, pancreas, lungs, and kidneys. Excess iron can be toxic to the body due to the formation of harmful free radicals that can damage cells and tissues. An increase in excessive ROS can result in the saturation of the antioxidant system. The presence of free radicals can lead to damage and the occurrence of filtration dysfunction in the glomerulus.

Effect of Intravenous Iron Administration on Bone Mineral and Iron Homeostasis in Patients with Inflammatory Bowel Disease-Results of a Prospective Single-Centre Study.

Anaemia and bone metabolism alterations are common in inflammatory bowel disease (IBD), which is a heterogeneous group of diseases that include Crohn's disease (CD) and ulcerative colitis (UC) with a rich intestinal and extraintestinal symptomatology. All these make the diagnostic procedures complicated and difficult. The aim of this study was to assess the effect of parenteral iron administration on biomarkers of mineral and bone homeostasis over time. The study was a single-centre non-randomised prospective study. It was carried out between 2016 and 2020 in a group of patients in the Department of Internal Medicine and Gastroenterology Subunit of Inflammatory Bowel Diseases at the National Institute of Medicine of the Ministry of the Interior and Administration in Warsaw. At the first examination, the baseline disease severity, initial evaluation of anaemia (morphology, iron (Fe), total iron binding capacity (TIBC), ferritin, vitamin B12, folic acid) and bone mineral metabolism including C-reactive protein (CRP), albumins, alkaline phosphatase (ALP), Calcium, osteocalcin, phosphate in serum and in urine, parathyroid hormone (PTH), vitamin D3, fibroblast growth factor (iFGF23) and procollagen type 1N propeptide (P1NP) C-terminal telopeptide (CTX), was initially assessed. On the basis of peripheral blood counts, an appropriate dose of iron (iron derisomaltose or caboxymaltose) was administered. During the subsequent appointments on week 1, 4, and 12 morphology, iron (Fe), total iron binding capacity (TIBC), ferritin, vitamin B12, folic acid, C-reactive protein (CRP), albumins, alkaline phosphatase (ALP), Calcium, osteocalcin, phosphate in serum and in urine, parathyroid hormone (PTH), vitamin D3, fibroblast growth factor (iFGF23) and procollagen type 1N propeptide (P1NP) C-terminal telopeptide (CTX), were evaluated. A total of 56 patients were enrolled into the study: 24 women and 32 men. In the group, 32 patients had Crohn's disease (CD) and 24 had ulcerative colitis (UC). We found a statistically significant increase in the concentration of albumin (p = 0.031), haemoglobin (p < 0.001), haematocrit (p < 0.001), MCV (p < 0.001), MCHC (p = 0.001), iron (p < 0.001) and ferritin (p < 0.001) after the administration of parenteral iron. The influence of individual iron formulations on the analysed parameters (phosphate concentration in serum and in the urine, iFGF23, P1NP, PTH, vitamin D, haemoglobin and ferritin) was similar. Interestingly, an inverse correlation was found between the concentration of phosphorus in the blood and iFGF23 at certain time-points; however, in the study group they did not significantly affect the disturbances of calcium and phosphate metabolism. In the study group, transient and non-significant disorders of phosphate metabolism were found, which does not constitute a contraindication to treatment with parenteral iron in inflammatory bowel disease patients, which was safe and efficient.

TMPRSS6 gene mutations in six Saudi families with iron refractory iron deficiency anemia

Iron-refractory iron deficiency anemia (IRIDA) is considered an autosomal recessive iron deficiency anemia due to mutations in the transmembrane protease serine 6 (TMPRSS6) gene. Variations in iron parameters and a higher risk of iron deficiency have been linked to the TMPRSS6 mutations. Furthermore, human genome-wide association studies (GWAS) identified a common mutation (rs855791) linked to abnormal hematological parameters, highlighting the importance of the TMPRSS6 gene in the regulation of iron homeostasis. This is the first study to investigate TMPRSS6 gene mutation in six Saudi families of probands with iron deficiency anemia unresponsive to oral iron and partially responsive to parenteral iron administration. Each participant provided a vacutainer tube with three blood samples (2.5 ml each) and analyzed based on hematological, biochemical iron profiles, and followed by genotyping by PCR. The TMPRSS6 gene was amplified, sequenced, and analyzed in all probands and family members. Statistical analysis was done using SPSS and SHEsis software. Few functional mutations in these families were suggested (p.W73X, p.E523K and p.V736A). The proband of family 6 presented numerous hematological abnormalities upon initial consultation, including normocytic anemia accompanied by low Hb, normal MCV, low serum iron, low serum ferritin, and normal TIBC. While the p.W73X variant was only found in 2 families, the p.V736A variant was found in all examined Saudi families with IRIDA. Given the evidence outlined for these six cases, future genotype-phenotype correlation studies in a large number of IRIDA patients in Saudi Arabia may be very informative for patient management, in addition to increasing knowledge of TMPRSS6 function during development as well as factors in the regulation of TMPRSS6 and its effect on iron levels in the body.

Impact of intravenous iron on cardiac and skeletal oxidative stress and cardiac mitochondrial function in experimental uraemia chronic kidney disease.

Introuction: Uraemia leads to changes in cardiac structure, metabolic remodeling and anaemia, key factors in the development of heart failure in patients with chronic kidney disease. Previous studies have identified abnormalities in mitochondrial function, potentially impairing energy provision and enhancing oxidative stress. This study characterised oxidant status and changes in mitochondrial function in uraemia and the impact of correcting anaemia via intravenous iron therapy. Methods: Experimental uraemia was induced in male Sprague-Dawley rats via a subtotal nephrectomy and parenteral iron administration given 6 weeks post-surgery. Oxidative stress from tissue samples was evaluated by measuring pro-oxidant activities and anti-oxidant capacities in both sham and uraemic animals with and without iron supplementation. Thiobarbituric acid-reactive substances (TBARS), aconitase activity and cardiolipin were measured. Mitochondrial function was assessed using the Seahorse XFp analyser on isolated mitochondria excised from cardiac tissue. Results: Oxidative stress in this uraemic model was increased in cardiac tissue (increased GSSG/GSH ratio, TBARS and increased activities of pro-oxidant enzymes). There was no impact on skeletal tissue. Parenteral iron ameliorated oxidative stress by enhancing the anti-oxidant defense system in cardiac tissue and skeletal tissue. Examination of respiratory reserve in cardiac mitochondria demonstrated that parenteral iron restored mitochondrial function. This experimental model of uraemia demonstrated a specific oxidative stress on the heart muscle without significant changes in skeletal oxidant status. Iron therapy improved anti-oxidant defence system, consequently reducing oxidative stress in the heart and skeletal tissue. There was an improvement in cardiac mitochondrial function. Conclusions: This experimental evidence indicates that iron therapy could reduce vulnerability to oxidative stress and potentially improve both cardiac and skeletal functional capacity from improvements in mitochondrial function.

Peroral iron supplementation can be provided to piglets through a milk cup system with results comparable to parenteral iron administration.

The objective of this study was to investigate if iron can be allocated to piglets through sow milk replacer fed in a milk cup system with efficacies comparable to intramuscular (IM) administration of 200 mg gleptoferron. Two hundred and ninety-four piglets from 21 litters were allocated to three different iron treatments (n = 98). The treatments were 1) Control (CON) provided no supplemental iron, 2) Injected iron (II) provided 200 mg gleptoferron IM on day 3 postpartum, and 3) Milk iron (MI) provided sow milk replacer “DanMilk Supreme” added 1 % “Piglet Boozt” ad libitum from day 0 until 21 days postpartum. All piglets had access to dry feed from day 6. Initial and final body weight was registered and hemoglobin (Hb) levels were analyzed on day 0, 3, 7, 10, 17, and 21 after farrowing. In order to correlate drinking pattern with Hb level and growth, video cameras were installed, and drinking pattern was recorded on day 18 postpartum. A blood sample was drawn from piglets from three litters per treatment on day 21 for a complete hematology profile. The results showed that iron treatment had an effect on Hb levels (P < 0.001) that were different between all groups from day 10, resulting in a mean Hb level of 76.2 g/L (CON), 120.9 g/L (II), and 105.4 g/L (MI) on day 21. The mean Hb level for both MI and II was above the anemia threshold of 90 g/L and the Hb level of the II group was above 110 g/L and the piglets thus defined as normal. Treatment had a significant effect on Hb, hematocrit (hct), mean corposcular volume (MCV), mean corpuscular hemoglobin (MCH), red blood cell distribution width (RDW), lymphocytes (%), neutrophils (bill/L) (P < 0.05), neutrophils (%) (P < 0.01), with CON being significantly different from MI and II that were similar or tended to differ. Total visits at the cup was not correlated to Hb level (r = 0.08) and growth was not affected by treatment (P = 0.99). It is concluded that iron can be supplemented to piglets through a milk cup system with efficacies comparable to parenteral administration of 200 mg gleptoferron.

Anemia in the inpatient settings: what is left out of sight

Background. Anemia is a decrease in the number of erythrocytes and hemoglobin levels as a result of blood loss, disruption of erythropoietic cell production, and increased erythrocyte breakdown or a combination thereof. Anemia of pregnant women is divided into physiological anemia and pathological conditions. In case of latent iron deficiency clinical manifestations are absent. This condition is characterized by a decrease in iron and erythropoietin to a level sufficient to maintain hematological parameters at the lower limit of normal values. In the absence of iron supplements administrations 65 % of cases of latent deficiency end up in a manifest deficiency.&#x0D; Objective. To describe the features of the anemia treatment in inpatient settings.&#x0D; Materials and methods. Analysis of literature sources on this issue.&#x0D; Results and discussion. The normal value of hemoglobin for the 1st and 3rd trimesters is ≥110 g/l, for the 2nd – ≥105 g/l. After childbirth, anemia is determined as a decrease in hemoglobin &lt;100 g/l. Risk factors for anemia in pregnant women include poor nutrition, chronic diseases, chronic intoxication, history of anemia, bleeding during pregnancy, multiple pregnancy, frequent childbirth with a long lactation period, and short intervals between births. Anemia in pregnant women increases the probability of premature birth by 63 %, of low birth weight – by 31 %, of perinatal mortality – by 51 %, of neonatal death – in 2.5 times. In case of maternal anemia, the newborn has a worse development of external respiratory function, a lag in the weight gain and a greater susceptibility to infectious diseases. To diagnose anemia, a general blood test and determination of additional indicators (serum iron, ferritin, ferritin saturation, transferrin, soluble ferritin receptor) are used. Patients with mild anemia do not require hospitalization; patients with moderate anemia need hospitalization in the absence of a response to oral iron supplements; patients with severe anemia need hospitalization after the mandatory consultation of hematologist. The purposes of anemia treatment include the normalization of blood tests, correction of iron deficiency, and the creation of iron stores to ensure full fetal development and lactation. Evaluation of treatment is performed on the 21st day after treatment; normally the increase in hemoglobin is about 1 g per 1 day of therapy. If hemoglobin has increased by &lt;10 g/l, it is advisable to prescribe intravenous iron. Indications for parenteral administration also include the intolerance to oral iron supplements, peptic ulcer disease in the exacerbation phase, lack of confidence in the good adherence of the patient, hemodialysis, swallowing disorders, and the need for a more pronounced increase in hemoglobin. If it is necessary to quickly restore the level of blood hemoglobin in the late stages of pregnancy, Sufer (“Yuria-Pharm”) can be administered (10.0 ml in 200.0 ml of saline intravenously 1-3 times a week). Parenteral administration of iron supplements should be administered with caution in case of polyvalent allergies, active infections, chronic liver disease, and signs of iron overload. Parenteral administration of iron supplements is not indicated in the 1st trimester of pregnancy.&#x0D; Conclusions. 1. Anemia in pregnant women increases the likelihood of premature birth, low birth weight, perinatal mortality, and neonatal death. 2. The purposes of anemia treatment are the normalization of blood tests, correction of iron deficiency and the creation of iron stores. 3. Indications for parenteral administration of iron are lack of response and intolerance to oral iron supplements, exacerbation of the peptic ulcer disease, and the need for a more pronounced increase in hemoglobin. 4. If it is necessary to quickly restore the level of hemoglobin in the late stages of pregnancy, Sufer may be prescribed.

Hypophosphatemia: Collateral damage in parenteral iron administration

Hypophosphatemia: Collateral damage in parenteral iron administration

The Effects of Parenteral Iron Administration on Thyroid Hormones, Hematology, Oxidative Stress Characteristics, Performance, and Health in Neonatal Holstein Calves.

The present study investigated the effect of iron supplementation on thyroid hormones concentrations, oxidative stress characteristics, complete blood count (CBC) and serum biochemistry, and performance and health in calves of two groups: test group (n = 17, intramuscular injection of 500mg iron-dextran on the 2nd day of life) and control group (n = 17, intramuscular injection of normal saline at the same time). Blood samples were taken from all of the calves instantly after birth and at 7, 14, 21, 28, and 90days of age. Duration of treatment for diseases, body weight, height, and length were measured at each sampling time to evaluate growth and health. The results indicated that age (sampling time) had a significant effect (p ≤0.05) on the values of all measured variables except for ferric reducing ability of plasma (FRAP) amount and band neutrophil number. The treatment (group) had no significant effect on the amount of measured variables. Significant interactions between sampling time and group were found for white blood cell count (WBC), adult neutrophil, and bilirubin amounts (p ≤0.05). Significant higher amounts of hematocrit (HCT) and hemoglobin (Hb) at day 28 and mean corpuscular volume (MCV) at day 7 were seen in the test group compared with control group. Test group in comparison with control group had significantly lower amount of WBC at day 7; mean corpuscular hemoglobin concentration (MCHC), band neutrophils, and lymphocytes at day 14; and number of platelets at day 28. Growth and total weight gain and mean daily gain had no significant differences between the two groups. The duration of treatment for pneumonia and diarrhea was not significantly different between trial groups. The results show that parenterally administration of iron to newborn calves had no effect on improving erythropoiesis, performance, thyroid metabolism, oxidative/antioxidative situation, and health of dairy calves.

P0851THE DIFFERENTIAL IMPACT OF INTRAVENOUS IRON IN A MODEL OF EXPERIMENTAL URAEMIA ON TISSUE MARKERS OF OXIDATIVE STRESS

Abstract Background and Aims Uraemia leads to changes in cardiac structure, metabolic remodelling and anaemia, key factors in the development of heart failure in patients with chronic kidney disease (CKD). Previous studies have identified abnormalities in mitochondrial function in experimental uraemia, potentially impairing energy provision and enhancing oxidative stress. The aim of this study was to characterise oxidant status and changes in mitochondrial function in uraemia and the impact of iron therapy. Method Experimental uraemia was induced in male Sprague-Dawley rats via a subtotal nephrectomy and parenteral iron administration at 6 weeks post-surgery (10mg/Kg body weight). Pro-oxidant activities and antioxidant capacities (oxidised glutathione (GSSG) relative to reduced (GSH)) in both sham and uraemic animals and lipid peroxidation (thiobarbituric acid-reactive substances (TBARS) was measured. Mitochondrial function was assessed using the SEAHORSE analyser. Results Oxidative stress was increased in cardiac tissue (69% increase in GSSG/GSH ratio, 38% rise in TBARS and significantly (79%) upregulated NADPH oxidase activity. Glutathione peroxidase (GPx) and glutathione reductase (GR) activities were significantly increased by 30%. Iron reduced GSSG/GSH ratio and TBARS by 62% and 51% respectively. Iron therapy was also associated with significantly increased aconitase activity. Parenteral iron improved respiratory reserve in cardiac mitochondria and skeletal mitochondria suggests IV iron restores mitochondrial function. Conclusion Uraemia leads or oxidative stress and mitochondrial dysfunction in cardiac tissue. Iron therapy reduces oxidative stress and improves cardiac mitochondrial function. This might lead to reduced adverse cardiovascular outcomes in CKD.

Effects of Parenteral Supply of Iron and Copper on Hematology, Performance, and Health in Neonatal Dairy Calves

The objective of this present study was to examine the effects of parenteral administration of iron and copper on hematological parameters, growth, and health of dairy calves in the period when iron and copper deficiency could exist.

Iron metabolism and iron-refractory iron deficiency anemia

Hepcidin is a key molecule that regulates iron metabolism in the body. Iron refractory iron deficiency anemia (IRIDA) is a genetic disorder caused by a defect in the TMPRSS6 gene encoding matriptase-2, a transmembrane serine protease that physiologically inhibits hepcidin production. In patients with IRIDA, the iron uptake in the intestine is remarkably reduced, and iron deficiency anemia (IDA) develops. However, in contrast to the ordinary IDA, high hepcidin levels in IRIDA keep the serum ferritin levels normal or sometimes high. Due to the malabsorption of iron in the intestine, IRIDA is refractory to oral iron supplementation, but partially responds to parenteral iron administration. A high hepcidin level gives IRIDA a lot of similarities with anemia of chronic disease, and a differential diagnosis between the two disorders needs careful inspection. Diagnosis of IRIDA needs genetic testing that is hardly available in most facilities, and therefore its clinical features are not fully understood.

Comparison of Oral and Parenteral Iron Administration on Iron Homeostasis, Oxidative and Immune Status in Anemic Neonatal Pigs

The present study was to evaluate the consequences of iron status across oral and parenteral iron administrations in prevention of iron deficiency anemia. A total of 24 one-day-old male neonatal piglets were allocated into three groups given non-iron supplementation (NON), intramuscular iron dextran injection (FeDex), and oral administration of ferrous glycine chelate (FeGly), respectively. At day 8, no significant differences in final body weight, average weight gain, and tissue coefficients were observed among three groups (P > 0.05). Both oral FeGly and FeDex injection significantly increased serum iron, ferritin, hemoglobin, and tissue iron deposition (P < 0.05). However, FeDex-injected supplementation resulted in rapidly rising hepcidin levels and hepatic iron deposition (P < 0.05). In addition, compared to parenteral iron supplementation, greater serum IgA level, SOD, and GSH-Px activities, lower expressions of IL-1β and TNF-α in the liver, and lower expressions of IL-6 and TNF-α in the spleen were found in oral iron piglets (P < 0.05). According to our results, oral administration of ferrous glycine chelate improved iron homeostasis, and oxidative and immune status in anemic neonatal pigs.

Safety of Intravenous Iron - Cosmofer and Monofer Therapy in Peritoneal Dialysis and Non-Dialysis-Dependent Chronic Kidney Disease Patients.

Safety of parenteral iron therapy is critical and has been demonstrated in several studies, but concerns persist on safety. We performed a retrospective single-center study investigating the safety and efficacy of parenteral iron administration using 2 iron preparations-Monofer and Cosmofer (Pharmacosmos A/S, Holbaek, Denmark)-in patients with chronic kidney disease (CKD), on peritoneal dialysis (PD) and non-dialysis. A database of CKD patients receiving intravenous (IV) iron was analyzed. Side effects were recorded during infusion, post-infusion, and after 48 hours. In a population of CKD patients (non-dialysis and PD), IV iron is safe with few major adverse effects for these 2 IV iron preparations studied with similar dosing schedules. These data provide reassurance on the relative short-term safety of IV iron preparations regarding acute infusion-related hypersensitivity reactions.

The Effects of Chronic Iron Overload in Rats with Acute Acetaminophen Overdose.

Rats are resistant to acetaminophen (APAP) hepatotoxicity. In this study, we evaluated whether by augmentation of the hepatic oxidative stress, through the induction of hepatic iron overload (IO), it will be feasible to overcome the resistance of rats to the toxic effects of APAP. Rats with no or increased hepatic IO. Providing iron by diet induced hepatocellular IO, while parenteral iron administration induced combined hepatocellular and sinusoidal cell IO. APAP administration to rats with no IO caused an increase in hepatic oxidative stress and a decrease in the hepatic antioxidative markers but no hepatic cell damage. APAP administration to rats with hepatocellular IO further amplified the hepatic oxidative stress but induced only hepatocyte feathery degeneration without any increase in serum aminotransaminases. APAP administration to rats with combined hepatocellular and sinusoidal cell IO caused an unexpected decrease in hepatic oxidative stress and increase in the hepatic antioxidative markers and no hepatic cell damage. No hepatic expression of activated c-jun-N-terminal kinase was detected in any of the rats. The hepatic distribution of iron may affect its oxidative/antioxidative milieu. Augmentation of hepatic oxidative stress did not increase the rats' vulnerability to APAP.

Iron deficiency and iron treatment in the fetal developing brain \u2013 a pilot study introducing an experimental rat model

BackgroundIron deficiency is especially common in women during the reproductive age and it is estimated that 52% of pregnant women have iron deficiency anemia. Maternal iron deficiency with or without anemia in pregnancy may have consequences for the fetus, where it may have an impact on the cerebral development of the brain. Both animals and adult human studies support that iron deficiency affects psychomotor development, behavioral traits, and cognitive functions in the offspring. However, it has not yet been established whether the availability of sufficient iron is particularly important in certain phases during brain development, and whether possible damages are reversible if iron supplementation is provided during pregnancy. Here we report results from a pilot study in an experimental rat model suitable for introducing iron deficiency in the fetal rat brain.MethodsThe model was utilized for examination of the potential to reverse changes in fetal brain iron by maternal parenteral iron administration. Fertilized females subjected to iron deficiency without anemia were subcutaneously injected with iron isomaltoside at the day of mating (E0), 14 days into pregnancy (E14), or at the day of birth (Postnatal (P) 0). Blood, brain and liver in the offspring were examined on P0 or in adulthood on postnatal day P70.ResultsMaternal iron restriction during pregnancy led to significantly lower levels of iron in the brains of newborn rats compared to levels in pups of iron sufficient mothers. Females fed ID diet (5.2 mg/kg Fe) had offspring with significantly lower cerebral iron compared to a control group fed a standard diet (158 mg/kg Fe). Injection of IIM to pregnant ID females on E0 or E14 yielded normalization of Fe in the developing brain known to express elevated levels of capillary transferrin receptors, indicating that the administered iron passed the placenta and fetal blood brain barrier.ConclusionsIn future studies, this translational model may be applied to examine morphological and biochemical consequences of iron deficiency and iron deficiency treatment in the developing fetal brain.

Management of Perinatal Iron Deficiency Anemia: A Retrospective Review of a Community Based Intervention [18P

INTRODUCTION: Unresolved iron-deficiency anemia in pregnancy contributes to maternal and neonatal morbidity, which may be preventable by iron administration. Kaiser Permanente San Francisco (KPSF) Perinatal Anemia Management Program (PAMP) developed a comprehensive algorithmic approach to identify and treat iron-deficiency anemia. A retrospective observational study was conducted to assess the impact of PAMP on peripartum anemia prior (1/2012-6/2013), during (9/2013-2/2015) and after (3/2015-8/2016) its implementation. METHODS: Iron-deficient anemic pregnant women delivering at KPSF were identified during the above time periods and divided into cohorts who received prenatal care at KPSF, exposed to PAMP versus KPSF satellites, not exposed to PAMP. Data for 2nd, 3rd trimester and delivery hemoglobin values, parenteral iron administrations and blood transfusions were electronically extracted and analyzed using Chi-square statistics, t-tests, ANOVA, and non-parametric tests to compare differences among groups. RESULTS: The mean % change in hemoglobin was significantly higher during-PAMP and post-PAMP among women receiving prenatal care at KPSF compared to women who received prenatal care at satellites (PAMP: 14.6 vs. 12.7, p&lt;0.01; post-PAMP: 15.2 vs. 13.1, p&lt;0.01). The number of KPSF women receiving parenteral iron was highest during PAMP (n=63) and remained constant for satellite women for the three time periods (n=4). Finally, the number of blood transfusions sequentially decreased by period regardless of place of prenatal care (pre-PAMP: n=25, PAMP: n=13, post-PAMP: n=11). CONCLUSION: The PAMP comprehensive approach was associated with improvements in peripartum iron-deficiency anemia, increased parenteral iron administration and a decrease in blood transfusions. Implementation of similar programs may in turn lower maternal and neonatal morbidity.

Iron Supplementation: What's New?

Supplemental orally-administered iron has been available for centuries, but parenteral administration of iron as a therapeutic agent dates from the 1930s. The original agents were iron salts, and their administration to man was associated with severe and unacceptable side-effects even with doses of 4-8 mg. The modern-day practice of IV iron supplementation was transformed in the 1940s with the introduction of iron incorporated into a carbohydrate shell, to allow slow release in the circulation and rapid binding to plasma transferrin. The older iron-carbohydrate complexes included iron dextran, iron sucrose, and iron gluconate, with different iron release kinetics. Iron dextran had significant toxicity with possible anaphylactic reactions. Other iron preparations can also induce hypersensitivity reactions, although recent evidence suggests that these are not immunoglobulin-mediated, but may be due to free iron in circulation or mediated via complement, the so-called CARPA reactions (complement activation-related pseudo-allergy). Newer oral iron preparations include ferric citrate which is much more tolerable than ferrous sulphate, while newer IV iron compounds include ferric carboxymaltose, iron isomaltoside 1000 , and ferumoxytol. Iron supplementation has traditionally been used to ameliorate iron deficiency anaemia, and in the early 1990s, IV iron was found to be mandatory in dialysis patients to support erythropoiesis under stimulation with recombinant human erythropoietin. Recent data also suggest that IV iron may have benefits in chronic heart failure, independent of any effect on haemoglobin or red cell production, possibly by enhancing cardiac myocyte mitochondrial function. Although most RCTs suggest better efficacy with IV iron versus oral iron, there are some concerns regarding the safety of parenteral iron, not only in relation to hypersensitivity reactions, but also exacerbation of oxidative stress or infections. Several ongoing RCTs are seeking to provide further evidence in this regard, e.g. the PIVOTAL trial. Newer strategies for replenishing iron stores include HIF prolyl hydroxylase inhibitors (HIF PHIs), antagonists of the hepcidin pathway, or dialysate iron administration as ferric pyrophosphate citrate. HIF PHIs (such as roxadustat and vadaddustat) have been shown to reduce hepcidin, probably indirectly via stimulation of erythropoiesis, as well as by stimulating a number of iron-regulatory genes, and allowing greater amounts of iron to be absorbed orally. Many molecules designed to interfere with hepcidin activity are in varying stages of clinical development, including monoclonal antibodies against hepcidin or its signalling pathway, spiegelmers, anticalins, and antisense oligonucleotides. Administering ferric pyrophosphate citrate (Triferric™) across dialysis has recently become clinical reality in the US, although this is not available in Europe. Thus, strategies to supplement iron have developed considerably over the last two decades, with several novel approaches transitioning from bench to bedside. DisclosuresMacdougall:Astellas: Honoraria, Research Funding; GlaxoSmithKline: Consultancy; Akebia: Consultancy; Vifor Pharma: Consultancy, Honoraria, Research Funding, Speakers Bureau; Pharmacosmos: Honoraria; AMAG: Consultancy, Honoraria, Research Funding; FibroGen: Consultancy, Speakers Bureau.

Iron supplementation in Switzerland - A bi-national, descriptive and observational study.

Iron deficiency is the most common nutritional disorder in the world, and it is the only common nutrient deficiency in industrialised nations. It is thought to be the most common cause of anaemia. Use of iron supplementation in Switzerland has not been previously quantified in detail. We quantified use of iron supplementation from Swiss data and compared it with data from the UK. We assessed the frequency of serum ferritin and haemoglobin tests prior to newly started iron therapy to see whether use was based on documented low iron levels or blood parameters, especially in the case of parenteral iron supplementation. We conducted a retrospective descriptive study of prescription iron supplementation use, and compared use of oral or parenteral iron drugs between Switzerland (CH) and the UK. We retrieved Swiss data from the Swiss Health Insurance Helsana Group, and UK data were from the Clinical Practice Research Datalink (CPRD). The study period was 2012 to 2014. The 3-year prevalence of iron supplementation was 9.4% in Switzerland and 4.4% in the UK. Iron use increased slightly between 2012 and 2014 in both countries (CH +0.3%, UK +0.2%). Recorded parenteral iron administration was roughly a thousand times higher in Switzerland (1.9%) than in the UK in 2014. In Switzerland, iron supplements were mostly given to patients aged 20 to 49 years or older than of 80 years. In the UK, iron supplementation was less frequent in younger people, but more prevalent in the elderly. Prior to a first iron prescription, ferritin tests were done more frequently in Switzerland (oral 67.2%, parenteral 86.6%) than in the UK (oral 43.3%, parenteral 65.5%). Haemoglobin was measured before a new parenteral iron therapy rarely in Switzerland (oral 14.9%, parenteral 11.7%), but frequently in the UK (oral 77.4%, parenteral 85.6%). Iron supplementation is more common in Switzerland than in the UK, particularly parenteral iron supplementation. Haemoglobin measurements prior to a new parenteral iron therapy are relatively infrequent in Switzerland despite the required documentation of haemoglobin prior to therapy.