Serum Hepcidin Concentrations Research Articles

Predictive value of serum markers for postacne scarring.

Postacne scarring is the main concern of many acne patients. Predicting the liability to scarring can alter the management protocols and help in preventing such disfigurement. Sixty patients with moderate to severe acne vulgaris (according to Global Acne Grading system) were included, only 35 of them had postacne scars. A quantitative latex agglutination commercial kit was used to assess serum C-reactive protein (CRP) concentration by turbidimetry, while serum hepcidin concentration was assessed by a commercially available double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) kit. Patients with postacne scarring had significantly lower serum levels of hepcidin (P-value < .001) and significantly higher serum levels of CRP (P-value < .05). Serum levels of hepcidin and CRP are promising markers, which may be considered as objective tools to predict the possibility of postacne scarring.

Serum Hepcidin Concentrations Decline during Pregnancy and May Identify Iron Deficiency: Analysis of a Longitudinal Pregnancy Cohort in The Gambia

BackgroundAntenatal anemia is a risk factor for adverse maternal and fetal outcomes and is prevalent in sub-Saharan Africa. Less than half of antenatal anemia is considered responsive to iron; identifying women in need of iron may help target interventions. Iron absorption is governed by the iron-regulatory hormone hepcidin. ObjectiveWe sought to characterize changes in hepcidin and its associations with indexes of iron stores, erythropoiesis, and inflammation at weeks 14, 20, and 30 of gestation and to assess hepcidin's diagnostic potential as an index of iron deficiency. MethodsWe measured hemoglobin and serum hepcidin, ferritin, soluble transferrin receptor (sTfR), and C-reactive protein (CRP) at 14, 20, and 30 wk of gestation in a cohort of 395 Gambian women recruited to a randomized controlled trial. Associations with hepcidin were measured by using linear regression, and hepcidin's diagnostic test accuracy [area under the receiver operating characteristic curve (AUCROC), sensitivity, specificity, cutoffs] for iron deficiency at each time point was analyzed. ResultsThe prevalence of anemia increased from 34.6% at 14 wk of gestation to 50.0% at 20 wk. Hepcidin concentrations declined between study enrollment and 20 wk, whereas ferritin declined between 20 and 30 wk of gestation. The variations in hepcidin explained by ferritin, sTfR, and CRP declined over pregnancy. The AUCROC values for hepcidin to detect iron deficiency (defined as ferritin <15 μg/L) were 0.86, 0.83, and 0.84 at 14, 20, and 30 wk, respectively. Hepcidin was superior to hemoglobin and sTfR as an indicator of iron deficiency. ConclusionsIn Gambian pregnant women, hepcidin appears to be a useful diagnostic test for iron deficiency and may enable the identification of cases for whom iron would be beneficial. Hepcidin suppression in the second trimester suggests a window for optimal timing for antenatal iron interventions. Hemoglobin does not effectively identify iron deficiency in pregnancy. This trial was registered at www.isrctn.com as ISRCTN49285450.

Iron Supplementation During 3 Consecutive Days Of Endurance Training Augmented Hepcidin Concentration

PURPOSE: Several physiological mechanisms have been proposed to explain impaired iron status, such as gastrointestinal bleeding, hemolysis, lack of iron in dietary diet and losses in sweat. However, detailed mechanisms underlying exercise-induced iron deficiency among athletes remain unclear. Hepcidin, the 25-amino acid peptide hormone, is a key mediator of iron homeostasis and it may represent another mechanism for iron deficiency in response to exercise training.The present study was designed to investigate impact of consecutive days of strenuous endurance training on hepcidin concentration. The influence of iron supplementation during training period was also determined. METHODS: Fourteen male endurance athletes (long distance runners, triathletes) participated (mean ± standard error, age: 19-22 yrs ; height: 1.68 ± 0.01m ; body mass: 57.3 ± 1.6 kg; maximal oxygen uptake (VO2max): 59.6 ± 0.8 ml/kg/min). Subjects were randomly assigned to either an iron treatment group (Fe group, n=7) or a placebo group (CON group, n=7). All subjects completed 3 consecutive days of endurance training, consisting of two bouts of 75 min of treadmill running at 75 % of VO2max, separated with 3h of rest between bouts. In the Fe group, 12 mg of iron was provided using flavor drink twice a day (24 mg/day), whereas the subjects in the CON group took the same flavor drink without iron. Venous blood samples were collected in early morning on days1-4 and 3h after second bout of exercise on day1. Serum hepcidin, ferritin, iron, myoglobin and plasma IL-6 concentrations were evaluated. RESULTS: The Fe and CON groups showed acute elevations of serum hepcidin, myoglobin and plasma IL-6 concentrations 3h after exercise (P < 0.05 vs. baseline). After 3 days of training period (day4), serum hepcidin concentration was significantly higher in Fe group than in CON group (11.0 ± 2.5 ng/mL vs. 5.9 ± 1.6 ng/mL, P < 0.05). Moreover, serum iron concentration was decreased only in Fe group on day 4 (91.3 ± 13.5 in the Fe group vs. 129.7 ± 7.4 μg/dL in the CON group). CONCLUSIONS: Three consecutive days of endurance training increased hepcidin concentration at baseline when the iron was supplemented.

432 - Altered iron regulation after extended acute reperfused ST-segment-elevation myocardial infarction

Information regarding the changes of iron regulation at the acute phase and during the first few months following acute reperfused ST-segment-elevation myocardial infarction (MI) is scarce. However, changes in hepcidin, the major regulatory protein responsible for iron homeostasis, and other partners of iron status may occur. We assayed iron, transferrin, ferritin and hepcidin serum concentrations in a subgroup of patients of the PREGICA patient collection 4 ± 2 days (D4) and 6 months (M6) after a first ST+ MI with at least 3 akinetic LV segments at echocardiography performed at D4. Patients were classified as exhibiting myocardial hemorrhage (MH, n = 8), microvascular obstruction (MVO, n = 14), both (HVO, 47) or none of these deleterious conditions (C, n = 18) according to MRI performed at D4, and as remodelers (R) or non-remodelers (NR) when their LVEDV increased (R) or did not change or decreased (NR) between D4 and M6, respectively. Serum iron concentration increased from D4 to M6 in all patients (P

Low Serum Retinol Concentration Explain Higher Hepcidin Levels In Mexican Older Adults

BackgroundElevated hepcidin levels have been linked to anemia of inflammation (AI). Retinol deficiency has shown to modulate hepcidin expression in animals; however, no studies have explored low serum retinol (LSR) concentration in older adults (OA) and their possible association with hepcidin concentrations. Anemia affect 27% of Mexican OA and inflammation may play a role in the production of anemia in this population. Understanding the mechanisms that play a role in the control hepcidin secretion is an important goal in the prevention of AI.AimTo explore if low serum retinol is associated with higher serum hepcidin concentrations in Mexican older adults (≥60years).MethodsMexican OA were participants in a crossectional study to identify the main causes of anemia. They were recruited in August 2015. Fasting serum samples were collected in 535 OA. Serum retinol (SR) was measured by HPLC and LSR was defined if SR&lt;20μg/dL. Hepcidin (ng/mL) was measured using a commercial ELISA kit. Due to skewed distribution of hepcidin, a quantil regression model was used to associate the LSR and hepcidin, adjusting by sex, age, BMI, ferritin, transferrin receptor, vitamin B12 status, IL‐6, C reactive protein, Alpha‐1‐acid glycoprotein, diabetes, hypertension, tertil of socioeconomic status, sarcopenia and functional disability.ResultsMean age was 71.5y for male and 70.7y for female. LSR was present in 3.2% of OA. Mexican OA with low serum retinol had 12.2 ng/mL higher hepcidin levels than OA with normal serum retinol levels (p=0.03). Hepcidin adjusted median (by confounders) were (median±EE): 19.4± 1.0 ng/mL in OA with normal serum retinol and 31.9±5.7 ng/mL in OA with LSR. Sarcopenic OA had higher hepcidin levels (coef: 7.5 ng/mL, p=0.03) than OA non‐sarcopenic.ConclusionsLSR levels in OA explain their higher hepcidin concentrations. Retinol concentrations affects iron homeostasis but the mechanism is unclear. This data document for the first time that in humans, low serum retinol concentration is inversely associated with hepcidin concentrations. Further longitudinal studies are needed to understand the role of serum hepcidin and Retinol in the development of AI in OA.Support or Funding InformationCONACYT‐FONSEC SSA/IMSS/ISSSTE SALUD 2014‐1, S0008‐2014‐1‐000000000234157

Serum Hepcidin and Soluble Transferrin Receptor in the Assessment of Iron Metabolism in Children on a Vegetarian Diet

The aim of this study was to assess the effect of vegetarian diet on iron metabolism parameters paying special attention to serum hepcidin and soluble transferrin receptor (sTfR) concentrations in 43 prepubertal children (age range 4.5–9.0 years) on vegetarian and in 46 children on omnivorous diets. There were no significant differences according to age, weight, height, and body mass index (BMI) between vegetarian and omnivorous children. Vegetarians had similar intake of iron and vitamin B12 and a significantly higher intake of vitamin C (p < 0.05) compared with non-vegetarians. Hematologic parameters and serum iron concentrations were within the reference range in both groups of children. Serum transferrin levels were similar in all subjects; however, ferritin concentrations were significantly (p < 0.01) lower in vegetarians than in omnivores. In children on a vegetarian diet, median hepcidin levels were lower (p < 0.05) but sTfR concentrations significantly higher (p < 0.001) compared with omnivorous children. In the multivariate regression model, we observed associations between hepcidin level and ferritin concentration (β = 0.241, p = 0.05) in the whole group of children as well as between hepcidin concentration and CRP level (β = 0.419, p = 0.047) in vegetarians. We did not find significant associations with concentration of sTfR and selected biochemical, anthropometric, and dietary parameters in any of the studied groups of children. As hematologic parameters and iron concentrations in vegetarians and omnivores were comparable and ferritin level was lower in vegetarians, we suggest that inclusion of novel markers, in particular sTfR (not cofounded by inflammation) and hepcidin, can better detect subclinical iron deficiency in children following vegetarian diets.

Hepcidin and iron parameters in children with anemia of chronic disease and iron deficiency anemia

BackgroundAnemia of chronic disease (ACD) and iron deficiency anemia (IDA) are the two most prevalent forms of anemia having interrelated characteristics. Hepcidin, a newly introduced biomarker for assessment of iron status, is a homeostatic regulator of iron metabolism. We investigated the role of hepcidin and other conventional iron parameters to assess iron status among children with ACD and IDA. We also identified children with ACD who developed iron deficiency (ID).MethodsThe study was undertaken in anemic children with 30 cases each of ACD and IDA along with 30 age and sex-matched controls. The ACD cases were subdivided into pure ACD and ACD with coexistent ID. All cases were subjected to following tests: complete blood count with peripheral smear, serum C-reactive protein, serum interleukin-6, iron studies, serum soluble transferrin receptor (sTfR), and serum hepcidin.ResultsThe mean serum hepcidin concentration was significantly increased in pure ACD patients (143.85±42.76 ng/mL) as compared to those in IDA patients (6.01±2.83 ng/mL, P < 0.001) and controls (24.96±9.09 ng/mL, P <0.001). Also, compared to pure ACD patients [normal sTfR levels (<3 µg/mL)], the serum hepcidin concentration was reduced significantly in ACD patients with ID [high sTfR levels (≥3 µg/mL)] with a mean of 10.0±2.97 ng/mL.ConclusionHepcidin measurement can provide a useful tool for differentiating ACD from IDA and also help to identify an iron deficiency in ACD patients. This might aid in the appropriate selection of therapy for these patients.

Curcumin attenuates erythropoiesis in recombinant human erythropoietin-induced polycythemia in rats

Background: Several studies documented the non-hematologic clinical therapeutic uses of recombinant human erythropoietin (EPO). On the other hand, hypertension, thromboembolism, and increased oxidative stress were toxic effects related to the increased hematocrit (Hct) with recombinant human EPO treatment. Accordingly, alternate strategies to reduce erythropoietic activity and other potential side effects of EPO will greatly improve its non-hematopoietic clinical applicability. Aims and Objectives: Our objective was to demonstrate whether curcumin treatment could attenuate the effect of recombinant human EPO on erythropoiesis in EPO-induced polycythemia, and if so, whether this effect is mediated by changing concentrations of iron and its key regulator hormone hepcidin in rats. Materials and Methods: Totally 24 male albino Sprague-Dawley rats were included in this study. Rats were equally divided into four groups: Control group, curcumin-treated group, EPO-induced polycythemia group, and curcumin + EPO-induced polycythemia group. Blood indices and serum concentrations of iron, ferritin, and hepcidin were measured. Results: EPO treatment caused significant increase in hemoglobin (Hb), red blood cells, and Hct versus other study groups (P < 0.05). Curcumin treatment significantly decreased Hct in curcumin-treated group versus control and EPO-induced polycythemia groups (P = 0.021 and 0.008, respectively). Serum iron concentrations were significantly decreased in curcumin + EPO-induced polycythemia group versus control group. Serum ferritin concentrations were significantly decreased in all treated groups versus the control group. Serum hepcidin concentrations were significantly decreased in EPO-induced polycythemia group and curcumin + EPO-induced polycythemia group versus control group. Conclusion: The presented data suggest a potentially attenuating effect of curcumin administration on recombinant human EPO-induced polycythemia. This effect may be mediated by promoting iron deficiency. However, further studies are required to address the safety of this combination treatment and interspecies differences in iron metabolism between rats and human in addition to have better understanding of the role of the hepcidin.

Evaluation of Hepcidin and Atherosclerosis in Dialysis Patients.

Chronic kidney disease (CKD) is a condition that involves 10% - 15% of population worldwide, which increases the risk of cardio-vascular diseases (CVD). Chronic kidney disease is one of the main reasons for illness and mortality in the world. Chronic kidney disease is a serious health problem caused by involvement of a large number of patients with kidney injury, especially in industrial countries. Among the main reasons for this are population living longer and the number of diseases in elderly persons, such as diabetes mellitus type 2, hypertension, and cardio-vascular diseases. We evaluated 63 patients on chronic dialysis at the Dialysis Centre at University "Aleksandrovska" Hospital; the average age was 49.9 ± 7.8. Their results were compared to 63 age matched controls. Blood samplings were taken before dialysis procedure. In the included groups, we measured CBC, serum iron (by Ferrozine method), ferritin, soluble transferrin receptors and hsCRP (by nephelometric method), hepcidin (by ELISA method), and homocysteine (by CLIA method). IMT was measured by using electronic calipers and evaluated by automated software programs. We established elevated serum hepcidin levels in CKD patients (205.1 ± 29.9 µg/L) compared to the control group (20.8 ± 3.1 µg/L), p < 0.001. Serum homocysteine and hsCRP concentrations were elevated in CKD cases (48.7 ± 6.8 µmol/L; 29.7 ± 4.1 mg/L) compared to controls (7.9 ± 1.8 µmol/L; 1.1 ± 0.4 mg/L), p < 0.005. In patients with CKD we found a strong positive correlation between serum hepcidin and homocysteine concentrations, r = 0.879, p < 0.001. In patients with impaired kidney function soluble transferrin receptors correlated negatively to hepcidin: r = -0.799, p < 0.001. In dialysis, the transferrin concentration correlated highly positive to hepcidin: r = 0.691, p < 0.001. IMT in CKD patients correlated positively to hepcidin and homocysteine levels: r = 0.788 and r = 0.841, respectively, p < 0.005. Chronic kidney disease is connected to cardio-vascular disease risk factors. CKD might be an independent CVD risk factor. In early kidney injury stages, increased morbidity is found from CVD. The risk of fatal and non-fatal cardio-vascular incidents is connected to kidney injury. For clinical practice, early evaluation of hepcidin and atherosclerosis in chronic kidney disease patients is very important.

Normalizing serum hepcidin but not α-1-antitrypsin level during effective treatment of chronic hepatitis C.

Aim of the studyWe investigated the impact of pegylated interferon α-2 in combination with ribavirin (PEG-IFNα/RBV) treatment on hepcidin and α-1-antitrypsin concentrations in the serum of patients with chronic hepatitis C.Material and methodsWe measured serum concentrations of hepcidin, prohepcidin and α-1-antitrypsin by enzyme-linked immunosorbent assays in patients with chronic hepatitis C before and during antiviral therapy.ResultsHepcidin concentrations were increased in both genotype 1b and 3a hepatitis C virus (HCV) infected patients as compared with the control group. During treatment of patients infected with genotype 1b HCV hepcidin levels gradually declined, reaching significantly lower values at the treatment termination than before therapy. Treatment responders showed an increased concentration of hepcidin at week 4 of therapy and a subsequent decrease to values significantly lower than observed among non-responders at week 48 of treatment. α-1-antitrypsin concentration was not affected by the treatment efficacy.ConclusionsSuccessful therapy of patients persistently infected with HCV was associated with restoration of serum hepcidin concentration to values similar to the control group. Differential dynamics of hepcidin during PEG-IFNα/RBV therapy in responders and non-responders might indicate the direct influence of viral eradication on iron homeostasis.

Effects of flaxseed oil on blood hepcidin and hematologic factors in hemodialysis patients

In hemodialysis (HD) patients, one of the common complications is renal anemia. Therefore, the present study was designed to investigate the effects of flaxseed oil consumption on blood hepcidin and hematologic factors in HD patients. In this randomized, double-blind, clinical trial, 38 HD patients were randomly assigned to either the flaxseed oil or the control group. The patients in the flaxseed oil group received 6 g/d flaxseed oil for 8 wk, whereas the control group received 6 g/d medium chain triglycerides (MCT) oil. At baseline and the end of week 8, serum hepcidin, and blood hemoglobin, hematocrit, red blood cells (RBCs), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) were measured after a 12- to 14-h fast. Flaxseed oil consumption significantly reduced serum hepcidin concentration up to 25% during 8 weeks, and the reduction was significant in comparison with the MCT oil group. In addition, the number of RBCs, blood hemoglobin, hematocrit, MCH and MCHC increased significantly in the flaxseed oil group up to 6%, 10%, 6%, 5%, and 2%, respectively, and these elevations were significant in comparison with the MCT oil group. There was no significant difference between the two groups in mean changes of MCV. This study indicates that daily consumption of 6 g flaxseed oil reduces serum hepcidin and improves hematologic factors in HD patients.

Meta-GWAS and Meta-Analysis of Exome Array Studies Do Not Reveal Genetic Determinants of Serum Hepcidin.

Serum hepcidin concentration is regulated by iron status, inflammation, erythropoiesis and numerous other factors, but underlying processes are incompletely understood. We studied the association of common and rare single nucleotide variants (SNVs) with serum hepcidin in one Italian study and two large Dutch population-based studies. We genotyped common SNVs with genome-wide association study (GWAS) arrays and subsequently performed imputation using the 1000 Genomes reference panel. Cohort-specific GWAS were performed for log-transformed serum hepcidin, adjusted for age and gender, and results were combined in a fixed-effects meta-analysis (total N 6,096). Six top SNVs (p<5x10-6) were genotyped in 3,821 additional samples, but associations were not replicated. Furthermore, we meta-analyzed cohort-specific exome array association results of rare SNVs with serum hepcidin that were available for two of the three cohorts (total N 3,226), but no exome-wide significant signal (p<1.4x10-6) was identified. Gene-based meta-analyses revealed 19 genes that showed significant association with hepcidin. Our results suggest the absence of common SNVs and rare exonic SNVs explaining a large proportion of phenotypic variation in serum hepcidin. We recommend extension of our study once additional substantial cohorts with hepcidin measurements, GWAS and/or exome array data become available in order to increase power to identify variants that explain a smaller proportion of hepcidin variation. In addition, we encourage follow-up of the potentially interesting genes that resulted from the gene-based analysis of low-frequency and rare variants.

Evaluation of Iron Overload in the Heart and Liver Tissue by Magnetic Resonance Imaging and its Relation to Serum Ferritin and Hepcidin Concentrations in Patients with Thalassemia Syndromes.

Iron overload is one of the major prognostic factor in thallassemia patients. We aimed to evaluate iron accumulation in the heart and liver by MRI in thalassemia major, thalassemia intermedia, and S-ß thalassemia patients and to examine its association with ferritin and hepcidin levels. Serum ferritin and hepcidin levels were recorded. Iron overload (IOL) in the heart and liver parenchyma was determined based on the standardized T2* and R2 values measured by MRI. The results were evaluated considering the tissue iron overload, serum ferritin and hepcidin levels. Comparing the 109 patients with the 30 healthy controls revealed the mean age: 24.4±11 versus 31.2±5years, median levels of serum ferritin: 1693 versus 40ng/mL, and hepcidin: 1.94 versus 0.355ng/mL; p<0.001, respectively. Comparison of age, serum ferritin and hepcidin levels and MRI findings of the patients with or without IOL revealed that, ferritin and T2* were significantly different in the patients with IOL in cardiac tissue (p=0.004 and p<0.001), and, age, ferritin and R2 were significantly different in the patients with IOL in liver tissue (p=0.036, p<0.001 and p<0.001). The MRI-based T2* and R2 values were moderately and inversely correlated with serum ferritin (r=-0.37; p<0.001 and r=-0.46; p<0.001). No correlations were found between the MRI-based T2*, R2 values and serum hepcidin. A moderate and positive correlation existed between serum ferritin and hepcidin (r=0.45; p<0.001). We considered that, enhanced intestinal iron absorption characterized by decreased serum hepcidin levels in the intervals between successive transfusions were resulted in iron accumulation in our patients.

Hepatic iron content is independently associated with serum hepcidin levels in subjects with obesity

Serum hepcidin concentration is known to increase in parallel to circulating markers of iron stores. We aimed to investigate whether this is reflected at the tissue level in subjects with obesity. Serum hepcidin and ferritin levels (ELISA) and hepatic iron content (using magnetic resonance imaging) were analyzed longitudinally in 44 participants (19 without obesity and 25 with obesity). In a subgroup of 16 participants with obesity, a weight loss intervention was performed. Serum hepcidin, ferritin and hepatic iron content (HIC) were significantly increased in participants with obesity. Age- and gender-adjusted serum hepcidin was positively correlated with BMI, hsCRP, ferritin and HIC. In addition, age- and gender-adjusted serum hepcidin was positively correlated with ferritin and HIC in both non-obese and obese participants. In multivariate regression analysis, hepatic iron content (p<0.01) and serum ferritin (p<0.001) contributed independently to circulating hepcidin concentration variation after controlling for age, gender, BMI and hsCRP. Diet intervention-induced weight loss led to decreased serum hepcidin (p=0.01), serum ferritin concentration (p=0.01) and HIC (p=0.002). Of note, the percent change of serum hepcidin strongly correlated with the percent change of serum ferritin (r=0.69, p=0.01) and HIC (r=0.61, p=0.03) even after controlling for age and gender. Serum hepcidin is a reliable marker of the hepatic iron content in subjects with obesity.

Micronutrient intake, from diet and supplements, and association with status markers in pre- and post-RYGB patients

Roux-en-Y gastric bypass (RYGB) is associated with an increased risk for micronutrient deficiencies. This study aimed to assess total (dietary and supplement) intake and association with iron (including hepcidin), vitamin B12, vitamin C and zinc status markers before and after Roux-en-Y gastric bypass (RYGB). This prospective study included patients with a planned RYGB in University Hospitals Leuven, Belgium; who were followed until 12 months post-RYGB. Patients completed an estimated dietary record of two non-consecutive days before and 1, 3, 6 and 12 months post-RYGB and supplement/drug use was registered. Associations between total micronutrient intake and status markers were analyzed. Fifty-four patients (21 males; mean age: 48.0 [95%CI 46.6; 49.3] years; mean preoperative BMI: 40.4 [95%CI 39.4; 41.4] kg/m2) were included. One month post-RYGB, usual dietary intake of the studied micronutrients was significantly decreased compared to pre-RYGB, but gradually increased until 12 months post-RYGB, remaining below baseline values. By including micronutrient supplement intake, 12 months post-RYGB values were higher than baseline, except for zinc. Hemoglobin, ferritin, vitamin B12 and C-reactive protein serum concentrations were significantly decreased and transferrin saturation and mean corpuscular volume were significantly increased 12 months post-RYGB. Serum hepcidin concentration was significantly decreased 6 months post-RYGB. Medical nutritional therapy is essential following RYGB as dietary intake of iron, vitamin B12, vitamin C, copper and zinc was markedly decreased postoperatively and some patients still had an inadequate total intake one year post-RYGB.

Iron Supplementation Affects Hematologic Biomarker Concentrations and Pregnancy Outcomes among Iron-Deficient Tanzanian Women

Background: Iron deficiency is a highly prevalent micronutrient abnormality and the most common cause of anemia globally, worsening the burden of adverse pregnancy and child outcomes.Objective: We sought to evaluate the response of hematologic biomarkers to iron supplementation and to examine the predictors of the response to iron supplementation among iron-deficient pregnant women.Methods: We identified 600 iron-deficient (serum ferritin ≤12 μg/L) pregnant women, aged 18–45 y, presenting to 2 antenatal clinics in Dar es Salaam, Tanzania using rapid ferritin screening tests, and prospectively followed them through delivery and postpartum. All women received 60 mg Fe and 0.25 mg folate daily from enrollment until delivery. Proportions meeting the thresholds representing deficient hematologic status including hemoglobin <110 g/L, ferritin ≤12 μg/L, serum soluble transferrin receptor (sTfR) >4.4 mg/L, zinc protoporphyrin (ZPP) >70 mmol/L, or hepcidin ≤13.3 μg/L at baseline and delivery were assessed. The prospective change in biomarker concentration and the influence of baseline hematologic status on the change in biomarker concentrations were assessed. Regression models were estimated to assess the relation of change in biomarker concentrations and pregnancy outcomes.Results: There was significant improvement in maternal biomarker concentrations between baseline and delivery, with increases in the concentrations of hemoglobin (mean difference: 15.2 g/L; 95% CI: 13.2, 17.2 g/L), serum ferritin (51.6 μg/L; 95% CI: 49.5, 58.8 μg/L), and serum hepcidin (14.0 μg/L; 95% CI: 12.4, 15.6 μg/L) and decreases in sTfR (−1.7 mg/L; 95% CI: −2.0, −1.3 mg/L) and ZPP (−17.8 mmol/L; 95% CI: −32.1, 3.5 mmol/L). The proportions of participants with low hemoglobin, ferritin, and hepcidin were 73%, 93%, and 99%, respectively, at baseline and 34%, 12%, and 46%, respectively, at delivery. The improvements in biomarker concentrations were significantly greater among participants with poor hematologic status at baseline – up to 12.1 g/L and 14.5 μg/L for hemoglobin and ferritin concentrations, respectively. For every 10-g/L increase in hemoglobin concentration, there was a 24% reduced risk of perinatal mortality (RR = 0.76; 95% CI: 0.59, 0.99) and a 23% reduced risk of early infant mortality (RR = 0.77; 95% CI: 0.60, 0.99). The risk of anemia at delivery despite supplementation was predicted by baseline anemia (RR = 2.11; 95% CI: 1.39, 3.18) and improvements in ferritin concentration were more likely to be observed in participants who took iron supplements for up to 90 d (RR = 1.41; 95% CI: 1.13, 1.76).Conclusion: Iron supplementation decreases the risk of maternal anemia and increases the likelihood of infant survival among iron-deficient Tanzanian pregnant women. Interventions to promote increased duration and adherence to iron supplements may also provide greater health benefits.

0135 : New regulators of iron metabolism, hepcidin and erythroferrone, in acute myocardial infarction

Dysfunctional iron storage and transport are common in patients with chronic heart failure and associated with poor prognosis. Body iron could contribute to the pathogenesis of coronary artery disease (CAD) through its ability to induce oxidative stress. However, studies on the relationship between iron metabolism and CAD have yielded conflicting results. from the obseRvatoire des Infarctus de Côte d’Or (RICO) survey, 31 consecutive patients admitted in Intensive Care Unit for a first AMI were included. Serum concentrations of iron, transferrin, ferritin, the iron-regulatory hormone hepcidin and erythroferrone (a new hepcidinregulating hormone), transferrin saturation and total iron binding capacity were assessed on admission. Mean age was 65±16 yrs, 61% were male, 51% had hypertension, 23% diabetes, 45% dyslipidemia and 32% were smokers. There was a trend toward a higher serum hepcidin concentration in men (99.8 versus 56.3 ng/ml, p=0.181). Heart rate on admission was negatively associated with an erythroferrone concentration (r=-0.428, p=0.023). Haemoglobin level and hematocrit were positively correlated with erythroferrone concentration (p=0.027 and p=0.021). Moreover, a lower serum transferrin concentration was found in patients with heart failure on admission (1.93±0.16 g/l, vs 2.32±0.42, p=0.001). Ferritin concentration was positively related with infarct size, as assessed by Creatine Kinase peak (r=0.535, p=0.002) and there was a trend toward a positive correlation with erythroferrone concentration (r=0.314, p=0.085). Elucidating the metabolic circuits regulated by peptidic hormones will provide valuable insights into complex networks governing iron availability in acute myocardial infarction. The author hereby declares no conflict of interest

Maternal and Cord Blood Hepcidin Concentrations in Severe Iron Deficiency Anemia

The present study was conducted to assess the maternal and cord blood hepcidin concentrations in severe iron deficiency anemia (IDA) and to find out its correlation with other iron status parameters. This prospective observational study was carried out in 30 mothers with severe IDA (hemoglobin < 70g/L and serum ferritin < 12μg/L), and 15 healthy nonanemic (hemoglobin ≥ 110g/L) mothers, who delivered live singleton neonates at term gestation. Mothers and neonates with infection/inflammatory conditions were excluded. Quantitative estimation of complete blood count, serum iron, ferritin, total iron binding capacity (TIBC), and transferrin saturation (Tfsat) was done in maternal and cord blood immediately after delivery by an auto analyzer. Serum hepcidin concentrations were measured by double-antibody sandwich enzyme-linked immunosorbent assay using a Human Hepcidin-25 kit. Data were analyzed by statistical software SPSS 16.0. The serum iron and ferritin concentrations in severe IDA were 6.7±1.8μmol/L and 4.1±1.4μg/L in maternal blood, and 9.5±2.6μmol/L and 55.4±19.7μg/L in cord blood, respectively, significantly lower than nonanemic controls (p<0.001). The corresponding serum hepcidin concentrations were 76.6±22.7μg/L and 110.5±11.8μg/L, respectively (p<0.05). The proportion of cord blood/maternal blood hepcidin concentration was similar in both anemic (1.4:1) and nonanemic (1.3:1) mothers. Significant correlation was observed among maternal and cord blood hepcidin concentrations and other iron status parameters. Even in the presence of low serum iron and ferritin, maternal and cord blood hepcidin concentrations remained high in severe anemia. Failure of this proportional suppression of hepcidin indicates poor systemic bioavailability of iron to the mother and poor placental transport.

Hepcidin and iron status in pregnant women and full-term newborns in first days of life

The amount of iron is regulated by hepcidin. The aim of the study was to assess hepcidin concentrations in healthy pregnant women before delivery, in cord blood, and in 3-day-old newborns in relation to maternal and neonatal iron status. The study group consisted of 44 mother-newborn pairs. Serum concentrations of hepcidin, ferritin, and transferrin receptor (sTfR) were assessed. Maternal hepcidin was significantly lower than cord blood (p < 0.001), and full-term newborn values (p < 0.001). Mothers also had the lowest ferritin and sTfR concentrations. The highest concentration of hepcidin was observed in the newborns. They had lower sTfR and higher ferritin concentrations than in cord blood (p < 0.001). Maternal ferritin correlated negatively with sTfR (R = -0.50 p = 0.005), and positively with hepcidin (R = 0.41; p = 0.005). There were no correlations between hepcidin and ferritin or sTfR concentrations in cord blood, nor between hepcidin and ferritin or sTfR concentrations in the newborns. Moreover, there were no correlations between maternal and cord blood or neonatal blood hepcidin, nor between maternal hepcidin and infant iron status. There were also no correlations between hepcidin in cord blood and hepcidin or parameters of the iron status in the children. It may be assumed that a relatively low concentration of hepcidin in women in late pregnancy facilitates their iron accumulation. Higher levels of hepcidin in full-term newborns than in their mothers may be the result of a relatively high level of iron from the stored supplies. Neonatal iron status was independently associated with either maternal or cord blood hepcidin.

GDF-15 and Hepcidin Levels in Nonanemic Patients with Impaired Glucose Tolerance.

Aims. Growth Differentiation Factor-15 (GDF-15) has been suggested as one of the regulators of hepcidin, an important regulatory peptide for iron deposition. Current data is conflicting about the relationship between hepcidin and disorders of glucose metabolism. We aimed to investigate serum hepcidin and GDF-15 concentrations and their associations with each other, in nonanemic subjects with impaired glucose tolerance (IGT) in comparison with the nonanemic subjects with normal glucose tolerance (NGT). Methods. Thirty-seven subjects with IGT and 32 control subjects with NGT, who were age-, gender-, and body mass index- (BMI-) matched, were included in the study. Results. Serum GDF-15 levels were significantly higher in IGT compared to NGT. There were no differences in hepcidin, interleukin-6, and high sensitive C-reactive protein levels between the groups. We found a positive correlation between GDF-15 and hepcidin levels. There were also positive correlations between GDF-15 and age, uric acid, creatinine, and area under the curve for glucose (AUC-G). Hepcidin was correlated positively with ferritin levels. In the multiple regression analysis, GDF-15 concentrations were independently associated with age, uric acid, and AUC-G. Conclusions. Impaired glucose tolerance is associated with increased GDF-15 levels even in the absence of anemia, but the levels of hepcidin are not significantly altered in prediabetic state.