Soluble Transferrin Receptor Concentrations Research Articles

Associations of maternal serum concentration of iron-related indicators with birth outcomes in Chinese: a pilot prospective cohort study

BackgroundPrevious studies of maternal iron and birth outcomes have been limited to single indicators that do not reflect the comprehensive relationship with birth outcomes. We aimed to investigate the relationship between maternal iron metabolism and neonatal anthropometric indicators using comprehensive iron-related indicators.MethodsA total of 914 Chinese mother-child dyads were enrolled in this prospective study. Subjects’ blood samples were collected at ≤ 14 weeks of gestation. Serum concentrations of iron-related indicators were measured by enzyme-linked immunosorbent assay (ELISA). Femur length was measured by B-ultrasound nearest delivery. Neonatal anthropometric indicators were collected from medical records.ResultsAfter adjustment for potential covariates, higher iron (per one standard deviation, SD increase) was detrimentally associated with − 0.22 mm lower femur length, whereas higher transferrin (per one SD increase) was associated with 0.20 mm higher femur length. Compared with normal subjects (10th-90th percentiles), subjects with extremely high (> 90th percentile) iron concentration were detrimentally associated with lower femur length, birth weight, and chest circumference, and a higher risk of low birth weight, LBW (HR: 3.92, 95%CI: 1.28, 12.0). Subjects with high concentration of soluble transferrin receptor, sTFR and transferrin (> 90th percentile) were associated with higher femur length. Subjects with low concentration of iron and ferritin concentrations (< 10th percentile) were associated with a higher risk of LBW (HR: 4.10, 95%CI: 1.17, 14.3) and macrosomia (HR: 2.79, 95%CI: 1.06, 7.35), respectively.ConclusionsMaternal iron overload in early pregnancy may be detrimentally associated with neonatal anthropometric indicators and adverse birth outcomes.

Association of Serum Soluble Transferrin Receptor Concentration With Markers of Inflammation: Analysis of 1001 Patients From a Tertiary Rheumatology Center.

Soluble transferrin receptor (sTfR) is considered to be a useful biomarker for the diagnosis of iron deficiency, especially in the setting of inflammation, as it is thought to not be affected by inflammation. We analyzed the relationship between sTfR levels and inflammatory markers in patients with known or suspected inflammatory rheumatic disease (IRD). Blood samples of 1001 patients with known or suspected IRD referred to a tertiary rheumatology center were analyzed. Study participants were classified as patients with active IRD and patients with inactive IRD or without IRD. Correlation analyses were used to explore the relationship between sTfR levels and inflammatory markers (ie, C-reactive protein [CRP], erythrocyte sedimentation rate [ESR]). We applied multiple linear regression analysis to evaluate the predictive value of CRP levels for sTfR concentrations after adjustment for potential confounding factors. There were positive correlations between inflammatory markers (CRP, ESR) and serum sTfR levels (ρ 0.44, ρ 0.43, respectively; P < 0.001), exceeding the strength of correlation between inflammatory markers and the acute phase reactant ferritin (ρ 0.30, ρ 0.23, respectively; P < 0.001). Patients with active IRD demonstrated higher serum sTfR levels compared to patients with inactive or without IRD (mean 3.99 [SD 1.69] mg/L vs 3.31 [SD 1.57] mg/L; P < 0.001). After adjustment for potential confounding factors, CRP levels are predictive for serum sTfR concentrations (P < 0.001). The study provides evidence against the concept that sTfR is a biomarker not affected by inflammation.

Associations of fish and meat intake with iron and anaemia in Malawian children.

Animal flesh foods are rich in bioavailable iron but infrequently consumed by young children. We aimed to determine whether flesh food intake was associated with iron and anaemia status among 585 Malawian infants enroled in a 6-month egg-feeding trial. The percentage of days of small fish, large fish and meat consumption were assessed through weekly 7-day animal-source food screeners. Grams of intake were assessed through 24-h recalls conducted at 6-9, 9-12 and 12-15 months of age. Plasma ferritin, soluble transferrin receptor (sTfR) and haemoglobin concentrations were measured at 6-9 and 12-15 months of age. Iron biomarkers were adjusted for inflammation during analysis. At enrolment, each flesh food category was consumed by <5% of children in the past 24 h. Over the next 6 months, small fish, large fish and meat were consumed on 25%, 8% and 6% of days, respectively, with mean usual intakes of <5 g/day. More frequent small fish consumption was associated with lower sTfR (geometric mean ratio [95% CI]: 0.98 mg/L [0.96, 1.00] per 10 percentage point difference) but not ferritin (1.03 µg/L [0.98, 1.07]) or haemoglobin (1.01 g/dL [1.00, 1.01]). Large fish consumption was associated with higher anaemia (prevalence ratio [95% CI]: 1.09 [1.01, 1.19]) and lower iron deficiency (0.96 [0.93, 1.00]) prevalence. Gram intakes of flesh food categories were not associated with any iron or anaemia indicators. Small fish were a primary contributor to flesh food intake in this cohort of Malawian children, although usual portions were small. Fish was associated with modest improvements to iron status, but meat was too infrequent to be associated with anaemia and iron deficiency.

Excessive Erythrocytosis Is Not Associated With Altered Iron Homeostasis in Men From the World's Highest City.

Excessive Erythrocytosis Is Not Associated With Altered Iron Homeostasis in Men From the World's Highest City.

Soluble transferrin receptor concentration compared with reticulocyte hemoglobin content as a reliable marker of iron deficiency anemia in hemodialysis patients

Abstract Introduction Adequate iron stores are necessary for successful erythropoiesis-stimulating agents (ESAs) therapy in hemodialysis (HD) patients. However, iron status estimation in HD patients remains challenging, as most parameters are affected by inflammation. We aimed to compare the performance of soluble transferrin receptor concentration (sTfR) and reticulocyte hemoglobin content (CHr) as potential markers for iron status assessment. Methods This was a cross-sectional study that included 60 anemic patients with kidney failure on regular HD for a minimum of 3 months. Patients were in the maintenance phase of the ESAs with stable doses for at least 4 weeks and at least 3 weeks free of iron therapy. Patients were classified into two groups; group I: 18 patients with noniron deficiency anemia (NIDA); transferrin saturation (TSAT) greater than 20% and ferritin greater than 200 ng/ml and group II: 42 patients with iron deficiency anemia (IDA); transferrin saturation less than 20% and/or ferritin less than 200 ng/ml. CHr and sTfR were evaluated as reliable markers for diagnosing iron deficiency. Results CHr was significantly lower while sTfR was significantly higher in patients with IDA. Based on the receiver operating characteristic (ROC) curve, the area under the curve (AUC) of sTfR was significantly larger than the area under the curve of CHr; however, this had a borderline significance. Conclusion sTfR has a significantly higher diagnostic power for diagnosis of IDA than CHr.

A randomised double-blind placebo-controlled clinical trial of oral hydroxyurea for transfusion-dependent \u03b2-thalassaemia

Hydroxyurea is an antimetabolite drug that induces fetal haemoglobin in sickle cell disease. However, its clinical usefulness in β-thalassaemia is unproven. We conducted a randomised, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of hydroxyurea in transfusion-dependent β-thalassaemia. Sixty patients were assigned 1:1 to oral hydroxyurea 10–20 mg/kg/day or placebo for 6 months by stratified block randomisation. Hydroxyurea treatment did not alter the blood transfusion volume overall. However, a significantly higher proportion of patients on hydroxyurea showed increases in fetal haemoglobin percentage (89% vs. 59%; p < 0.05) and reductions in erythropoietic stress as measured by soluble transferrin receptor concentration (79% vs. 40%; p < 0.05). Based on fetal haemoglobin induction (> 1.5%), 44% of patients were identified as hydroxyurea-responders. Hydroxyurea-responders, required significantly lower blood volume (77 ± SD27ml/kg) compared to hydroxyurea-non-responders (108 ± SD24ml/kg; p < 0.01) and placebo-receivers (102 ± 28ml/kg; p < 0.05). Response to hydroxyurea was significantly higher in patients with HbE β-thalassaemia genotype (50% vs. 0%; p < 0.01) and Xmn1 polymorphism of the γ-globin gene (67% vs. 27%; p < 0.05). We conclude that oral hydroxyurea increased fetal haemoglobin percentage and reduced erythropoietic stress of ineffective erythropoiesis in patients with transfusion-dependent β-thalassaemia. Hydroxyurea reduced the transfusion burden in approximately 40% of patients. Response to hydroxyurea was higher in patients with HbE β-thalassaemia genotype and Xmn1 polymorphism of the γ-globin gene.

Iron deficiency is an independent risk factor of increased myocardial energy expenditure in chronic heart failure patients

Chronic heart failure (CHF) is a major public health burden and is associated with high morbidity, mortality, and cost. Recent studies demonstrated iron metabolism and myocardial energy metabolism were altered in CHF patients. In this study, we aimed to analyze the effects and correlations of iron metabolism on myocardial energy metabolism in CHF. One hundred and thirty patients with CHF [age: 66.2±11.5 years, males: 58.5% and New York Heart Association (NYHA) class (II/III/IV): 67/43/20] were included. Serum concentrations of ferritin, transferrin saturation (Tsat), and soluble transferrin receptor (sTfR) were quantified as the indexes of iron metabolism, and echocardiography was used to assess myocardial energy expenditure (MEE) levels. Iron deficiency (ID) was defined as ferritin <100 or 100-300 µg/L with Tsat <20%. Patients with CHF were divided into two groups based on iron status. The prevalence of ID in CHF was 36.9%, and increased with the severity of CHF, reaching 80.0% in those with NYHA class IV (NYHA class II/III/IV: 17.9% vs. 46.5% vs. 80.0%, P=0.000). The demographic characteristics [age, sex, body mass index (BMI), blood pressure, and heart rate] and hemoglobin (HGB) concentrations in two groups were similar (all P>0.05). MEE was significantly higher in the ID group (92.7±23.0 vs. 65.6±20.8 cal/min, P=0.000), while NYHA classes II and III was significantly higher in the ID group (71.6±16.4 vs. 60.3±14.8 cal/min, P=0.022; 88.9±10.4 vs. 69.1±20.1 cal/min, P=0.000). In univariable linear regression models, the presence of ID, higher NYHA class, increased N-terminal pro-B-type natriuretic peptide (NT-proBNP), sTfR, left ventricular internal diastolic diameter (LVIDd), as well as reduced ferritin, Tsat levels, and lower left ventricular ejection fraction (LVEF) were associated with elevated MEE levels (all P<0.05). In multivariable regression models, the presence of ID, reduced Tsat. and increased sTfR remained independent predictors of elevated MEE levels after adjustment for all variables that showed a significant association with MEE (all P<0.05). The prevalence of ID is high in CHF and is associated with the severity of cardiac dysfunction. The presence of ID as well as reduced Tsat and increased sTfR concentrations are associated with elevated MEE levels in CHF.

Maternal Iron Status in Pregnancy and Child Health Outcomes after Birth: A Systematic Review and Meta-Analysis.

In pregnancy, iron deficiency and iron overload increase the risk for adverse pregnancy outcomes, but the effects of maternal iron status on long-term child health are poorly understood. The aim of the study was to systematically review and analyze the literature on maternal iron status in pregnancy and long-term outcomes in the offspring after birth. We report a systematic review on maternal iron status during pregnancy in relation to child health outcomes after birth, from database inception until 21 January 2021, with methodological quality rating (Newcastle-Ottawa tool) and random-effect meta-analysis. (PROSPERO, CRD42020162202). The search identified 8139 studies, of which 44 were included, describing 12,7849 mother–child pairs. Heterogeneity amongst the studies was strong. Methodological quality was predominantly moderate to high. Iron status was measured usually late in pregnancy. The majority of studies compared categories based on maternal ferritin, however, definitions of iron deficiency differed across studies. The follow-up period was predominantly limited to infancy. Fifteen studies reported outcomes on child iron status or hemoglobin, 20 on neurodevelopmental outcomes, and the remainder on a variety of other outcomes. In half of the studies, low maternal iron status or iron deficiency was associated with adverse outcomes in children. Meta-analyses showed an association of maternal ferritin with child soluble transferrin receptor concentrations, though child ferritin, transferrin saturation, or hemoglobin values showed no consistent association. Studies on maternal iron status above normal, or iron excess, suggest deleterious effects on infant growth, cognition, and childhood Type 1 diabetes. Maternal iron status in pregnancy was not consistently associated with child iron status after birth. The very heterogeneous set of studies suggests detrimental effects of iron deficiency, and possibly also of overload, on other outcomes including child neurodevelopment. Studies are needed to determine clinically meaningful definitions of iron deficiency and overload in pregnancy.

New Insights into Red Blood Cell Microcytosis upon mTOR Inhibitor Administration

The aim of this study was to evaluate the effect of everolimus, a mammalian target of rapamycin (mTOR) inhibitor, on red blood cell parameters in the context of iron homeostasis in patients with tuberous sclerosis complex (TSC) and evaluate its effect on cell size in vitro. Everolimus has a significant impact on red blood cell parameters in patients with TSC. The most common alteration was microcytosis. The mean MCV value decreased by 9.2%, 12%, and 11.8% after 3, 6, and 12 months of everolimus treatment. The iron level declined during the first 3 months, and human soluble transferrin receptor concentration increased during 6 months of therapy. The size of K562 cells decreased when cultured in the presence of 5 μM everolimus by approximately 8%. The addition of hemin to the cell culture with 5 μM everolimus did not prevent any decrease in cell size. The stage of erythroid maturation did not affect the response to everolimus. Our results showed that the mTOR inhibitor everolimus caused red blood cell microcytosis in vivo and in vitro. This effect is not clearly related to a deficit of iron and erythroid maturation. This observation confirms that mTOR signaling plays a complex role in the control of cell size.

Reticulocyte Haemoglobin Content and Soluble Transferrin Receptor Concentration as Markers of Iron Stores in Chronic Kidney Disease in Egyptian Patients

Background: Chronic kidney disease (CKD), also known as chronic renal disease, is progressive loss in kidney function over a period of months or years. It is an internationally recognized public health problem affecting 5–10% of the world population. Objective: To evaluate the role of reticulocyte hemoglobin content and soluble transferrin receptor concentration for detection of iron deficiency anemia in chronic kidney disease in Egyptian patients compared to conventional markers. Patients and Methods: This is a cross–sectional study that had been done on 177 Chronic Kidney Disease Egyptian patients with iron deficiency anemia. Patients had been selected from the Outpatient Clinics and Hemodialysis Unit of the Internal Medicine Department, Menoufia University Hospital. Subjects had been divided into three groups: group 1 (Hemodialysis group): A number of 49 chronic hemodialysis patients (more than 3 months), group 2 (CKD group): A number of 88 patients with chronic kidney disease stages 3-5 and group 3 (Controls): Included 40 healthy subjects as a control group and had been matched with other groups regarding age and gender. Results: There was statistically significant difference between the studied groups regarding serum iron, serum transferrin and serum ferritin. There was statistically significant difference between group I, II compared to control regarding total iron binding capacity (TIBC), Hb, reticulocyte hemoglobin content and serum soluble transferrin receptors (sTfR). Conclusion: This study concluded that sTfR, and TfR-F index proved to be important tools to determine iron deficiency anaemia (IDA) in RH anemic patients and TFR index has superior accuracy than sTfR.

Lack of association of HFE gene polymorphism with high body iron status in Pakistani patients with type 2 diabetes mellitus.

The Aim of this study was to investigate the relationship of 3 common polymorphisms in the HFE gene (C282Y, H63D and S65C) with high body iron status in a population of Pakistani subjects with type 2 diabetes mellitus (DM) and to explore if there is any novel mutation in HFE gene in a sample of Pakistani subjects with type 2 DM. In a case-control design, 200 healthy controls and 200 consecutive adult subjects with type 2 DM (both gender; age range of 30-70 years) were enrolled with informed consent. Their serum samples were analyzed for body iron status (ratio of concentration of soluble transferrin receptor to ferritin concentration). DNA from blood was screened for HFE gene polymorphisms via polymerase chain reaction, followed by restriction fragment length polymorphism or via Sanger sequencing to identify any novel mutation(s) in HFE gene. We found that there was lack of any association between HFE polymorphism and body iron status in Pakistani subjects with type 2 DM and healthy controls. H63D was the most common polymorphism found in this population. Single base substitution of G nucleotide instead of C at the codon position 187 in the HFE gene exon 2 was discovered in one subject with DM. There was also a lack of association between D allele (variant allele of H63D) and type 2 DM. A significant relationship was found between CG genotype and abnormal albuminuria in subjects with type 2 DM (p = 0.036). In conclusion, HFE gene polymorphism is not associated either with high body iron status or type 2 DM in a hospital based Pakistani population and variant allele of H63D polymorphism appears to be associated with diabetic nephropathy.

Characterisation of the types of anaemia prevalent among children and adolescents aged 1–19 years in India: a population-based study

Anaemia is a serious public health concern in India. However, national estimates for its prevalence are not available for the 5-14 years age group, nor are estimates available for the types of anaemia among children and adolescents (1-19 years). We aimed to assess the prevalence of anaemia among children and adolescents in India and to categorise types of anaemia on the basis of micronutrient deficiencies. We assessed the prevalence of anaemia among children (1-4 years and 5-9 years) and adolescents (10-19 years) using nationally representative data from the Comprehensive National Nutrition Survey. Anaemia was classified on the basis of age and sex-specific WHO cutoffs and serum ferritin, soluble transferrin receptor, folate, cyanocobalamin, and C-reactive protein concentrations as iron deficiency anaemia, folate or vitamin B12 deficiency anaemia, dimorphic anaemia (iron deficiency anaemia and folate or vitamin B12 deficiency anaemia), anaemia of other causes (anaemia not classified as iron deficiency anaemia and folate or vitamin B12 deficiency anaemia), and anaemia of inflammation. We included 26 765 children (11 624 aged 1-4 years and 15 141 aged 5-9 years) and 14 669 adolescents. In the weighted sample, anaemia prevalence was 40·5% (4553 of 11 233) among 1-4 year-olds, 23·4% (3439 of 14 664) among 5-9 year-olds, and 28·4% (4064 of 14 300) among adolescents. Among 2862 children aged 1-4 years, iron deficiency anaemia (1045 [36·5%]) was the most prevalent type, followed by anaemia of other causes (702 [24·5%]), folate or vitamin B12 deficiency anaemia (542 [18·9%]), dimorphic anaemia (387 [13·5%]), and anaemia of inflammation (186 [6·5%]). Among 2261 children aged 5-9 years, anaemia of other causes was the most common (986 [43·6%]), followed by folate or vitamin B12 deficiency anaemia (558 [24·6%]), iron deficiency anaemia (353 [15·6%]), dimorphic anaemia (242 [10·7%]), and anaemia of inflammation (122 [5·4%]). 861 (31·4%) of 2740 adolescents had anaemia of other causes, 703 (25·6%) had folate or vitamin B12 deficiency anaemia, 584 (21·3%) had iron deficiency anaemia, 498 (18·2%) and dimorphic anaemia, and 94 (3·4%) had anaemia of inflammation. Iron deficiency anaemia is the most common form of anaemia among younger children and anaemia of other causes among 5-9-year-old children and adolescents. Folate or vitamin B12 deficiency anaemia accounts for more than a third of anaemia prevalence. Anaemia prevention efforts should focus on strengthening the existing iron and folate supplementation programmes and prevention of folate or vitamin B12 deficiency anaemia. The Mittal Foundation.

Delayed iron improves iron status without altering malaria risk in severe malarial anemia

WHO guidelines recommend concurrent iron and antimalarial treatment in children with malaria and iron deficiency, but iron may not be well absorbed or utilized during a malaria episode. We aimed to determine whether starting iron 28 d after antimalarial treatment in children with severe malaria and iron deficiency would improve iron status and lower malaria risk. We conducted a randomized clinical trial on the effect of immediate compared with delayed iron treatment in Ugandan children 18 mo-5 y of age with 2 forms of severe malaria: cerebral malaria (CM; n=79) or severe malarial anemia (SMA; n=77). Asymptomatic community children (CC; n=83) were enrolled as a comparison group. Children with iron deficiency, defined as zinc protoporphyrin (ZPP) ≥ 80 µmol/mol heme, were randomly assigned to receive a 3-mo course of daily oral ferrous sulfate (2 mg · kg-1 · d-1) either concurrently with antimalarial treatment (immediate arm) or 28 d after receiving antimalarial treatment (delayed arm). Children were followed for 12 mo. All children with CM or SMA, and 35 (42.2%) CC, were iron-deficient and were randomly assigned to immediate or delayed iron treatment. Immediate compared with delayed iron had no effect in any of the 3 study groups on the primary study outcomes (hemoglobin concentration and prevalence of ZPP≥80 µmol/mol heme at 6 mo, malaria incidence over 12 mo). However, after 12 mo, children with SMA in the delayed compared with the immediate arm had a lower prevalence of iron deficiency defined by ZPP (29.4% compared with 65.6%, P=0.006), a lower mean concentration of soluble transferrin receptor (6.1 compared with 7.8 mg/L, P=0.03), and showed a trend toward fewer episodes of severe malaria (incidence rate ratio: 0.39; 95% CI: 0.14, 1.12). In children with SMA, delayed iron treatment did not increase hemoglobin concentration, but did improve long-term iron status over 12 mo without affecting malaria incidence.This trial was registered at clinicaltrials.gov as NCT01093989.

The diagnostic potential of the iron-regulatory hormone hepcidin.

The diagnostic potential of the iron-regulatory hormone hepcidin.

PS1299 SOLUBLE TRANSFERRIN RECEPTOR AND ITS FERRITIN INDEX IN COMPARISON WITH BIOCHEMICAL AND HEMATOLOGICAL PARAMETERS FOR THE DIFFERENTIATION OF ANEMIA STATES AND CORRELATION WITH IV IRON RESPONSE

Background:Soluble transferrin receptor (sTfR) increases in iron deficiency (ID), and is used as biomarker of tissue ID and bone marrow demand for iron. Iron‐deficient erythropoiesis is the most common cause of elevated sTfR. The sTfR is not significantly influenced by infection or inflammation and appears a useful marker in the differentiation of iron states in anemia. The sTfR/log10ferritin index (sTfR/logFerr) is directly proportional to the measurement of the functional and storage iron compartments and seems to fully assess body iron status. Hematological indices of hypochromia indicate impaired hemoglobin synthesis due to restricted iron delivery to erythrocyte precursors. Iron restriction to erythropoiesis is a common mechanism in iron deficiency anemia (IDA) and iron sequestration accompanying to some extent anemia of inflammation and chronic diseases (AICD). In combination with sTfR, hematological indices and other parameters of ID could provide evidence of increased bone marrow iron demand and iron‐restricted erythropoiesis (IRE), that may benefit from iv iron treatment, and help to avoid unnecessary iron therapy.Aims:The aim of this study was to assess correlation between sTfR and biochemical markers of iron status and hematological indices in patients with anemia states and low serum iron, referred to our Clinic for treatment, and to investigate the association of baseline sTfR and sTfR/logFerr index with iron response.Methods:Patients over 18 years were prospectively recruited and after clinical history and examination, blood tests including hematological indices and biochemical markers were performed. Diagnostic investigations and iv iron supplementation were prescribed as appropriate. Patients were classified as: iron deficiency anemia (IDA), anemia of inflammation and chronic disease (AICD), or the combined state of IRE with AICD (IRE/AICD) using clinical findings, traditional biochemical parameters and red cell indices. To determine the iron response, the full blood count was repeated at 7 and 14 days. Serum concentration of sTfR was measured via chemiluminescent immunoassay (Access1 sTfR immunoassay system, Beckman Coulter), a new routine parameter in our laboratory, and sTfR/logFerr index was calculated.Results:The sTfR immunoassay proved a good analytical reliability. The characteristics of the patients classified in the 3 types of anaemia are shown in a table. Numbers are given as median (10–90 percentiles).Soluble transferrin receptor concentrations and sTfR/logFerr correlated significantly with mean corpuscular hemoglobin (MCH). Level of sTfR was more than 2.1 mg/l (ULN) in 32 of 35 patients with IDA, in 12 of 16 patients with IRE/AICD, and in 7 of 30 patients with AICD. Calculated sTfR/logFerr was more than 2 in 31 of 35 patients with IDA and only in 3 of 16 patients with IRE/AICD and 1 patient with AICD. There were moderate correlations between sTfR and other anemia parameters (Hb, MCV, CHr, transferrin, TSAT), but low linear association with serum ferritin and no association with CRP was found. From 57 patients treated with iv iron, 37 responded (increase of Hb&gt;10 g/l by 2 weeks) and 20 failed to achieve an adequate increase of hemoglobin. There was correlation between iron response and sTfR and sTfR/logFerr index.Summary/Conclusion:A negative strong correlation exists between sTfR and MCH. The majority of patients had impaired hemoglobin synthesis and correspondingly high sTfR concentrations. The increased sTfR and sTfR/logFerr index correlated with subsequent iv iron response in the anemic patients and may provide help in their therapeutic management.image

The Association of TMPRSS6 Gene Polymorphism and Iron Intake with Iron Status among Under-Two-Year-Old Children in Lombok, Indonesia.

Multiple common variants in transmembrane protease serine 6 (TMPRSS6) were associated with the plasma iron concentration in genome-wide association studies, but their effect in young children where anemia and iron deficiency (ID) were prevalent has not been reported, particularly taking account of iron intake. This study aims to investigate whether TMPRSS6 SNPs (rs855791 and rs4820268) and iron intake are associated with a low iron and hemoglobin concentration in under-two-year-old children. The study analyzed the baseline of a randomized trial (NUPICO, ClinicalTrials.gov NCT01504633) in East Lombok, Indonesia. Children aged 6–17 months (n = 121) were included in this study. The multiple linear regressions showed that TMPRSS6 decreased serum ferritin (SF) by 4.50 g/L per copy minor allele (A) of rs855791 (p = 0.08) and by 5.00 μg/L per copy minor allele (G) of rs4820268 (p = 0.044). There were no associations between rs855791 and rs4820268 with soluble transferrin receptor (sTfR) and hemoglobin (Hb) concentration (rs855791; p = 0.38 and p = 0.13, rs4820268; p = 0.17 and p = 0.33). The finding suggests the need for further studies to explore whether the nutrient recommendation for iron should be based on genetic characteristics, particularly for children who have mutation in TMPRSS6.

Rapid growth is a dominant predictor of hepcidin suppression and declining ferritin in Gambian infants.

Iron deficiency and iron deficiency anemia are highly prevalent in low-income countries, especially among young children. Hepcidin is the major regulator of systemic iron homeostasis. It controls dietary iron absorption, dictates whether absorbed iron is made available in circulation for erythropoiesis and other iron-demanding processes, and predicts response to oral iron supplementation. Understanding how hepcidin is itself regulated is therefore important, especially in young children. We investigated how changes in iron-related parameters, inflammation and infection status, seasonality, and growth influenced plasma hepcidin and ferritin concentrations during infancy using longitudinal data from two birth cohorts of infants in rural Gambia (n=114 and n=193). This setting is characterized by extreme seasonality, prevalent childhood anemia, undernutrition, and frequent infection. Plasma was collected from infants at birth and at regular intervals, up to 12 months of age. Hepcidin, ferritin and plasma iron concentrations declined markedly during infancy, with reciprocal increases in soluble transferrin receptor and transferrin concentrations, indicating declining iron stores and increasing tissue iron demand. In cross-sectional analyses at 5 and 12 months of age, we identified expected relationships of hepcidin with iron and inflammatory markers, but also observed significant negative associations between hepcidin and antecedent weight gain. Correspondingly, longitudinal fixed effects modeling demonstrated weight gain to be the most notable dynamic predictor of decreasing hepcidin and ferritin through infancy across both cohorts. Infants who grow rapidly in this setting are at particular risk of depletion of iron stores, but since hepcidin concentrations decrease with weight gain, they may also be the most responsive to oral iron interventions.

Relationships between Maternal Obesity and Maternal and Neonatal Iron Status.

Obesity in pregnancy may negatively influence maternal and infant iron status. The aim of this study was to examine the association of obesity with inflammatory and iron status in both mother and infant in two prospective studies in pregnancy: UPBEAT and SCOPE. Maternal blood samples from obese (n = 245, BMI ≥ 30 kg/m2) and normal weight (n = 245, BMI < 25 kg/m2) age matched pregnant women collected at approximately 15 weeks’ gestation, and umbilical cord blood samples collected at delivery, were analysed for a range of inflammatory and iron status biomarkers. Concentrations of C- reactive protein and Interleukin-6 in obese women compared to normal weight women were indicative of an inflammatory response. Soluble transferrin receptor (sTfR) concentration [18.37 nmol/L (SD 5.65) vs. 13.15 nmol/L (SD 2.33)] and the ratio of sTfR and serum ferritin [1.03 (SD 0.56) vs. 0.69 (SD 0.23)] were significantly higher in obese women compared to normal weight women (P < 0.001). Women from ethnic minority groups (n = 64) had higher sTfR concentration compared with white women. There was no difference in maternal hepcidin between obese and normal weight women. Iron status determined by cord ferritin was not statistically different in neonates born to obese women compared with neonates born to normal weight women when adjusted for potential confounding variables. Obesity is negatively associated with markers of maternal iron status, with ethnic minority women having poorer iron statuses than white women.

Impact of a modified version of baby-led weaning on iron intake and status: a randomised controlled trial

ObjectiveTo determine the iron intake and status of infants following a version of baby-led weaning (BLW) modified to prevent iron deficiency (Baby-Led Introduction to SolidS; BLISS) compared with those of...

Subclinical inflammation affects iron and vitamin A but not zinc status assessment in Senegalese children and Cambodian children and women - ERRATUM.

OBJECTIVE To assess the impact of the acute-phase response (APR) during inflammation on Fe, Zn and vitamin A biomarkers to allow accurate evaluation of micronutrient status in populations. DESIGN Ferritin (FER), soluble transferrin receptor (TfR), retinol-binding protein (RBP), Zn, α1-acid glycoprotein and C-reactive protein concentrations were measured. Correction factors (CF) for each biomarker were calculated as the ratio for groups at different stages of inflammation v. the reference group without inflammation.Setting/SubjectsSenegalese (n 594) and Cambodian schoolchildren (n 2471); Cambodian women of reproductive age (n 2117). RESULTS TfR was higher during the incubation phase (CF=1·17) and lower during early and late convalescence (CF=0·87 and 0·78). FER was higher during all phases (CF=0·83, 0·48 and 0·65, respectively). RBP was higher during incubation (CF=0·88) and lower during early convalescence (CF=1·21). No effect of inflammation on Zn status was found. CONCLUSIONS Inflammation led to overestimation of Fe status and underestimation of vitamin A status. The response of the biomarker for vitamin A status to inflammation depended on the vitamin A status of the populations. Surprisingly, the assessment of Zn status was hardly affected by inflammation. Different phases of the APR had opposite effects on the assessment of Fe status using TfR. More research is needed to define the correct methods to adjust for inflammation in nutritional studies.