Depleted Iron Stores Research Articles

Improvements in Electrophysiological Measures of Brain Function During Memory Processing in Rwandan Women Consuming Iron Biofortified Beans

Iron deficiency and iron deficiency anemia have been shown to have negative effects on behavioral and electroencephalographic (EEG) measures of cognitive function, with many of these being reversible with timely repletion. We report here results from a randomized, controlled, double‐blind efficacy feeding trial testing the hypothesis that iron repletion would produce improvements in measures of brain function during cognitive tasks. Participants (healthy females, 18–27 yrs, n = 239) screened for low iron status, were randomized to groups that consumed either a high‐iron‐biofortified (BB) or a normal‐iron bean (CN) for 20 weeks. A subsample (n = 47) performed tests of attention and memory with concurrent EEG at baseline (BL) and endline (EL). A total of 29 participants had depleted iron stores (serum ferritin < 20 mg/L) and were non‐anemic, and 18 were iron depleted and anemic (serum ferritin < 20 mg/L and hemoglobin < 12 g/dL). We focus here on the BL and EL EEG data from the recognition memory task. Participants studied a set of images and were tested with equal numbers of studied (old) and unstudied (new) images, presented at test with 2, 3, or 4 cues. Dependent measures were the amplitude and latency of the P2 component (the earliest EEG feature that distinguishes old and new items), along with power in the θ‐ (4–7 Hz) and γ‐bands (> 30 Hz), which have been shown to distinguish old and new items and to index effortful attention in recall. Data were analyzed using 2 (time: BL, EL) by 2 (condition: CN, BB) repeated‐measures analyses of variance, run separately for new and old items. In addition, each dependent measure was regressed onto number of cues and condition, separately for new and old items at BL and EL. Significant (all p < .05) time by condition interactions were obtained for P2 latencies for the new items, and for the P2 amplitudes and latencies, θ‐band power in the central electrodes, and γ‐band power in the frontal electrodes for the old items. Increases were observed for P2 amplitudes and θ‐ and γ‐band power, decreases were observed for P2 latencies, and all changes were largest for those consuming BB. Significant (all R2 > 0.15) effects of number of cues were obtained for old items at BL for γ‐band power in frontal and central electrodes, and for old items at EL for all of the dependent measures, with the effects being largest for those consuming BB. Increasing number of cues produced increases in P2 amplitudes, decreases in P2 latencies, and increases in θ‐ and γ‐band power, with those increases being largest for those consuming BB. Taken together, these results suggest that the consumption of BB improves brain function in the service of memory.Support or Funding InformationFunded by Harvest Plus.

Assessment of Pro Hepcidin and Related with Iron Profile on Hemodialysis Men Patients

Patients with renal failure in the final stages undergo the treatment by hemodialysis. Hemodialysis is used to reinstate the intracellular and extracellular fluid environment, by propagation of molecules in solution through a semipermeable membrane along an electrochemical concentration gradient. Blood catching in the dialysis machine and the recurrent phlebotomy may lead to losing about 1-3 g of iron per year. Prohepcidin hormone is an acute phase protein (type II) that plays a major role in the systemic iron irregularities as it is a mediator of anemia in inflammation and regulator of iron metabolism. This study aims to evaluate the effect of hemodialysis on iron hemostasis and its relationship with prohepcidin as an inflammatory marker. This study includes forty four adult male patients with end-stage renal failure (in pre and post –treated) by means of chronic hemodialysis-HD with mean age (53.27 ± 13.76 years). The following biochemical investigations have been studied: Prohepcidin, Iron, Ferritin, Transferrin, Total Iron-Binding Capacity (TIBC), The Unsaturated Total Iron Binding Capacity (UIBC), and transferrin saturation (TAST).Decrement of Prohepcidin level on hemodialysis patients in post dialysis with non-significantly compared to pre dialysis, while iron and ferritin was increment in post treated than pre- treated with non-significantly.Hemodialysis affects Prohepcidin levels as it was long duration and Glomerular Filtration rate GFR (cock croft equation) and prohepcidin level affect the iron profile related with the iron store depletion.

Clinical Value of Hypochromia Markers in the Detection of Latent Iron Deficiency in Nonanemic Premenopausal Women.

Iron deficiency (ID) is the most common cause of anemia in fertile women and hemoglobin (Hb) within the reference interval does not exclude ID. The consequence of an imbalance between the iron requirements and supply is a reduction of red-cell Hb content, which causes hypochromic cells. The aim of this study was to assess the reliability of new parameters low Hb density (LHD%), reticulocyte Hb equivalent (RetHe), and percentage of hypochromic erythrocytes (%HypoHe) in the detection of latent ID (LID), defined as depletion of iron stores without anemia. Two hundred fifty consecutive nonanemic women in fertile age (18-40 years, mean 33.5 years), whose analyses had been requested by general practitioners, were included. Independent samples t-test, receiver operating characteristic (ROC) curve analysis (gold standard for detecting LID ferritin <30 μg/l), and Cohen's kappa index were applied. One hundred fifty-three women had ferritin within the reference range and Hb >120 g/L; 97 (38.8%) had LID. The results were as follows: %HypoHe-AUC 0.934, cutoff 1.6%, sensitivity 85.7%, specificity 92.1%; RetHe-AUC 0.914, cutoff 29.9 pg, sensitivity 86.8%, specificity 85.7%; LHD%-AUC 0.898, cutoff 5.0%, sensitivity 85.9%, specificity 84.1%. Applying those cutoffs, agreement between ferritin and %HypoHe was κ 0.61 and 0.56 for RetHe and LHD%. LHD%, %HypoHe, and RetHe emerge as reliable tests for the investigation of LID and could improve the ability to detect ID before anemia is present.

Impact of Multi-Micronutrient Fortified Rice on Hemoglobin, Iron and Vitamin A Status of Cambodian Schoolchildren: a Double-Blind Cluster-Randomized Controlled Trial.

In Cambodia, micronutrient deficiencies remain a critical public health problem. Our objective was to evaluate the impact of multi-micronutrient fortified rice (MMFR) formulations, distributed through a World Food Program school-meals program (WFP-SMP), on the hemoglobin concentrations and iron and vitamin A (VA) status of Cambodian schoolchildren. The FORISCA-UltraRice+NutriRice study was a double-blind, cluster-randomized, placebo-controlled trial. Sixteen schools participating in WFP-SMP were randomly assigned to receive extrusion-fortified rice (UltraRice Original, UltraRice New (URN), or NutriRice) or unfortified rice (placebo) six days a week for six months. Four additional schools not participating in WFP-SMP were randomly selected as controls. A total of 2440 schoolchildren (6–16 years old) participated in the biochemical study. Hemoglobin, iron status, estimated using inflammation-adjusted ferritin and transferrin receptors concentrations, and VA status, assessed using inflammation-adjusted retinol-binding protein concentration, were measured at the baseline, as well as at three and six months. Baseline prevalence of anemia, depleted iron stores, tissue iron deficiency, marginal VA status and VA deficiency were 15.6%, 1.4%, 51.0%, 7.9%, and 0.7%, respectively. The strongest risk factors for anemia were hemoglobinopathy, VA deficiency, and depleted iron stores (all p < 0.01). After six months, children receiving NutriRice and URN had 4 and 5 times less risk of low VA status, respectively, in comparison to the placebo group. Hemoglobin significantly increased (+0.8 g/L) after three months for the URN group in comparison to the placebo group; however, this difference was no longer significant after six months, except for children without inflammation. MMFR containing VA effectively improved the VA status of schoolchildren. The impact on hemoglobin and iron status was limited, partly by sub-clinical inflammation. MMFR combined with non-nutritional approaches addressing anemia and inflammation should be further investigated.

Assessment of Pro Hepcidin and Related with Iron Profile on Hemodialysis Men Patients

Patients with renal failure in the final stages undergo the treatment by hemodialysis. Hemodialysis is used to reinstate the intracellular and extracellular fluid environment, by propagation of molecules in solution through a semipermeable membrane along an electrochemical concentration gradient. Blood catching in the dialysis machine and the recurrent phlebotomy may lead to losing about 1-3 g of iron per year. Prohepcidin hormone is an acute phase protein (type II) that plays a major role in the systemic iron irregularities as it is a mediator of anemia in inflammation and regulator of iron metabolism. This study aims to evaluate the effect of hemodialysis on iron hemostasis and its relationship with prohepcidin as an inflammatory marker. This study includes forty four adult male patients with end-stage renal failure (in pre and post –treated) by means of chronic hemodialysis-HD with mean age (53.27 ± 13.76 years). The following biochemical investigations have been studied: Prohepcidin, Iron, Ferritin, Transferrin, Total Iron-Binding Capacity (TIBC), The Unsaturated Total Iron Binding Capacity (UIBC), and transferrin saturation (TAST).Decrement of Prohepcidin level on hemodialysis patients in post dialysis with non-significantly compared to pre dialysis, while iron and ferritin was increment in post treated than pre- treated with non-significantly.Hemodialysis affects Prohepcidin levels as it was long duration and Glomerular Filtration rate GFR (cock croft equation) and prohepcidin level affect the iron profile related with the iron store depletion.

The prevalence of anemia and iron deficiency is more common in breastfed infants than their mothers in Bhaktapur, Nepal

Background/Objectives:Iron deficiency anemia is a widespread public health problem, particularly in low- and middle-income countries. Maternal iron status around and during pregnancy may influence infant iron status. We examined multiple biomarkers to determine the prevalence of iron deficiency and anemia among breastfed infants and explored its relationship with maternal and infant characteristics in Bhaktapur, Nepal.Subjects/Methods:In a cross-sectional survey, we randomly selected 500 mother–infant pairs from Bhaktapur municipality. Blood was analyzed for hemoglobin, ferritin, total iron-binding capacity, transferrin receptors and C-reactive protein.Results:The altitude-adjusted prevalence of anemia was 49% among infants 2–6-month-old (hemaglobin (Hb) <10.8 g/dl) and 72% among infants 7–12-month-old (Hb <11.3 g/dl). Iron deficiency anemia, defined as anemia and serum ferritin <20 or <12 μg/l, affected 9 and 26% of infants of these same age groups. Twenty percent of mothers had anemia (Hb <12.3 g/dl), but only one-fifth was explained by depletion of iron stores. Significant predictors of infant iron status and anemia were infant age, sex and duration of exclusive breastfeeding and maternal ferritin concentrations.Conclusions:Our findings suggest that iron supplementation in pregnancy is likely to have resulted in a low prevalence of postpartum anemia. The higher prevalence of anemia and iron deficiency among breastfed infants compared with their mothers suggests calls for intervention targeting newborns and infants.

Genetic factors influencing ferritin levels in 14,126 blood donors: results from the Danish Blood Donor Study.

Many biologic functions depend on sufficient iron levels, and iron deficiency is especially common among blood donors. Genetic variants associated with iron levels have been identified, but the impact of genetic variation on iron levels among blood donors remains unclear. The effect of six single-nucleotide polymorphisms (SNPs) on ferritin levels in 14,126 blood donors were investigated in four genes: in Human Hemochromatosis Protein gene (HFE; rs1800562 and rs179945); in Transmembrane Protease gene, Serine 6 (TMPRSS6-regulating hepcidin; rs855791); in BTB domain containing protein gene (BTBD9-associated with restless legs syndrome; rs9357271); and in the Transferrin gene (TF; rs2280673 and rs1830084). Multiple linear and logistic regression analyses were used to evaluate the effect of each SNP on ferritin levels and the risk of iron deficiency (ferritin < 15 ng/mL). In HFE, the G-allele of rs1800562 was associated with lower iron stores in both sexes. This was also true for the C-allele of rs179945, but in men only. Also, the T-allele of TMPRSS6 rs855791 was negatively associated with iron stores in men. Homozygocity for C in rs1799945 was associated with iron deficiency in women. Results for all other genetic variants were insignificant. Genetic variants associated with hemochromatosis may protect donors against depleted iron stores. In addition, we showed that presence of the T-allele at rs855791 in TMPRSS6 was associated with lower iron stores in men.

Deranged iron status in psoriasis: the impact of low body mass.

BackgroundIron deficiency (ID) frequently complicates inflammatory-mediated chronic disorders, irrespective of anaemia. Psoriasis is a chronic, immune-mediated skin disease with systemic pro-inflammatory activation; thus, these patients may be prone to develop ID. ID adversely affects immune cells function, which can further contribute to disease progression. This study investigates iron status in psoriasis.MethodsSerum concentrations of ferritin, transferrin saturation (Tsat), soluble transferrin receptor (sTfR), and hepcidin were assessed as the biomarkers of iron status in 39 patients with psoriasis (17 men, age: 47 ± 10 years) and 44 healthy subjects (30 men, age: 53 ± 6 years).ResultsCompared with healthy controls, patients with psoriasis demonstrated similar haematologic status but deranged iron status as evidenced by decreased Tsat and elevated sTfR (negative tissue iron balance) and low levels of hepcidin (depleted iron stores) (all P < 0.05 vs. controls). In patients, the levels of interleukin-6 (level of pro-inflammatory activation) significantly correlated with hepcidin (R = 0.54), but not with ferritin, Tsat, and sTfR. Biomarkers reflecting ID were not associated with the severity of the disease (assessed with the Psoriasis Area and Severity Index) but significantly correlated low body mass index (BMI). Patients with BMI < 24 kg/m2 compared with those with BMI ≥ 24 kg/m2 demonstrated lower levels of ferritin (40 ± 30 vs. 186 ± 128 ng/mL, P < 0.001) and hepcidin (4.9 ± 2.3 vs. 10.7 ± 6.7 ng/mL, P = 0.03).ConclusionPsoriasis is associated with deranged iron status characterized by depleted iron stores with concomitant unmet cellular iron requirements. The magnitude of these abnormalities is particularly strong in patients with low body mass index. Whether iron deficiency may become a therapeutic target in psoriasis needs to be investigated.

Iron status determination in pregnancy using the Thomas plot.

Physiological changes during pregnancy affect routine tests for iron deficiency. The reticulocyte haemoglobin equivalent (RET-He) and serum-soluble transferrin receptor (sTfR) assay are newer diagnostic parameters for the detection of iron deficiency, combined in the Thomas diagnostic plot. We used this plot to determine the iron status of pregnant women presenting for their first visit to an antenatal clinic in Bloemfontein, South Africa. Routine laboratory tests (serum ferritin, full blood count and C-reactive protein) and RET-He and sTfR were performed. The iron status was determined using the Thomas plot. For this study, 103 pregnant women were recruited. According to the Thomas plot, 72.8% of the participants had normal iron stores and erythropoiesis. Iron-deficient erythropoiesis was detected in 12.6%. A third of participants were anaemic. Serum ferritin showed excellent sensitivity but poor specificity for detecting depleted iron stores. HIV status had no influence on the iron status of the participants. Our findings reiterate that causes other than iron deficiency should be considered in anaemic individuals. When compared with the Thomas plot, a low serum ferritin is a sensitive but nonspecific indicator of iron deficiency. The Thomas plot may provide useful information to identify pregnant individuals in whom haematologic parameters indicate limited iron availability for erythropoiesis.

Cost-minimization analysis of the carboxymaltose ferric (i.v.) Compared with sacarato ferric (i.v.) in the treatment of anemia under suplementary health care perspective

Absolute iron deficiency related to depletion of iron stores or functional iron deficiency are the main causes of anemia, which can trigger hospitalization and even mortality. International guidelines recommend intravenous (IV) iron therapy for several chronic conditions. Intravenous iron is more effective, better tolerated, and improves the quality of life to a greater extent than oral iron supplements. Ferric carboxymaltose (FCM) and iron sucrose (IS) are IV iron drugs available in the Brazilian market. Considering this scenario the purpose of the study is to perform a cost minimization analysis of FCM versus IS under the supplementary health setting. Due to no non-inferiority study design comparing both IV therapies, a cost-minimization analysis was conducted. Treatment expenditures were accounted considering drugs acquisition costs and infusion related costs. Drugs ex-factory prices were obtained in official price list. Infusion fees were accessed through research conducted in 36 private hospitals distributed in service categories. In each institution the information collected was: place of infusion, materials, medical honoraries, room fee and price lists. An average patient was assumed (70kg; Hb≤10,5g/dL) which would receive a total iron dose of 1,000mg in both regimens. According to label, FCM can be administrated in a single dose whereas IS requires 5 infusions of 200 mg iron given up twice weekly. Deterministic one-way sensitivity analysis was performed. Costs were reported in Brazilian currency. Treatment cost for FCM (BRL927.69) was lower than IS (BRL 1,184.97), due to more infusions required for treatment with IS. The number and cost of the infusions were the most influential parameters in the analysis, and even with variations of ± 20% in all parameters, treatment results with FCM remained favorable. FCM represents a cost-saving option compared with other IV therapy alternative used in the management of anaemia in the Brazilian Supplementary Health System.

Prevalence of Iron Deficiency and Anemia among Young Children with Acute Diarrhea in Bhaktapur, Nepal.

Iron deficiency anemia is still common in children under five years of age and may impair their growth and cognitive development. Diarrhea is the second most common reason for seeking medical care for young children in Nepal. However, neither screening programs nor effective preventive measures for anemia and iron deficiencies are in place among children with diarrhea in many developing countries. The aims of this study were to determine the prevalence of anemia and iron deficiency and explore their associations with clinical, socioeconomic, and anthropometric parameters in Nepalese children. This was a cross-sectional study based on 1232 children, six to 35 months old, with acute diarrhea participating in a zinc supplementation trial. The mean (SD) hemoglobin was 11.2 g/dL (1.2). Anemia was found in 493 children (40%); this estimate increased to 641 (52%) when we adjusted for the altitude of the study area (hemoglobin <11.3 g/dL). One in every three children had depleted iron stores and 198 (16%) of the children had both depleted iron stores and anemia, indicating iron deficiency anemia. The prevalence of anemia among children presenting with acute diarrhea was high but the degree of severity was mainly mild or moderate. Iron deficiency explained less than half of the total anemia, indicating other nutritional deficiencies inducing anemia might be common in this population.

A Randomized Control Study to Evaluate Effects of Short-term Oral Iron Supplementation in Regular Voluntary Blood Donors.

Regular blood donation can lead to iron deficiency anaemia. Early recognition and reversal of excessive iron loss by iron supplementation may avoid symptomatic iron store depletion in blood donors. The aim of this study was to assess the efficacy of iron supplementation in maintaining the iron stores of voluntary blood donors. A total of 200 regular volunteers who donated twice in previous year were randomly divided into two groups. Iron: oral iron supplementation tablets of elemental iron as ferrous fumarate. Placebo group: glucose containing capsules, to be taken once daily for 21days after one unit of blood donation. Their hemogram, serum ferritin, red cell indices and red cell distribution width were determined at baseline and after 1month and at the time of next blood donation. Out of 200 volunteers enrolled 98 were assigned to iron group and rest 102 into placebo group. Total of 37% donors dropped out, yielding a dropout rate of 35% in iron group and 39% in the placebo group. The haemoglobin and ferritin levels showed significant improvement in iron group compared to placebo group (p<0.05). Three weeks of oral iron therapy (98.6mg elemental iron/day) was able to maintain iron stores at 1month after donation but was not sufficient to sustain the iron stores over a period of 3months. Thus there is need to evaluate increased dosage or duration of iron supplementation in maintaining the iron stores.

Iron homeostasis and pulmonary hypertension: iron deficiency leads to pulmonary vascular remodeling in the rat.

Iron deficiency without anemia is prevalent in patients with idiopathic pulmonary arterial hypertension and associated with reduced exercise capacity and survival. We hypothesized that iron deficiency is involved in the pathogenesis of pulmonary hypertension and iron replacement is a possible therapeutic strategy. Rats were fed an iron-deficient diet (IDD, 7 mg/kg) and investigated for 4 weeks. Iron deficiency was evident from depleted iron stores (decreased liver, serum iron, and ferritin), reduced erythropoiesis, and significantly decreased transferrin saturation and lung iron stores after 2 weeks IDD. IDD rats exhibited profound pulmonary vascular remodeling with prominent muscularization, medial hypertrophy, and perivascular inflammatory cell infiltration, associated with raised pulmonary artery pressure and right ventricular hypertrophy. IDD rat lungs demonstrated increased expression of hypoxia-induced factor-1α and hypoxia-induced factor-2α, nuclear factor of activated T cells and survivin, and signal transducers and activators of transcription-3 activation, which promote vascular cell proliferation and resistance to apoptosis. Biochemical examination showed reduced mitochondrial complex I activity and mitochondrial membrane hyperpolarization in mitochondria from IDD rat pulmonary arteries. Along with upregulation of the glucose transporter, glucose transporter 1, and glycolytic genes, hk1 and pdk1, lung fluorine-18-labeled 2-fluoro-2-deoxyglucose ligand uptake was significantly increased in IDD rats. The hemodynamic and pulmonary vascular remodeling were reversed by iron replacement (ferric carboxymaltose, 75 mg/kg) and attenuated in the presence of iron deficiency by dichloroacetate and imatinib, 2 putative treatments explored for pulmonary arterial hypertension that target aerobic glycolysis and proliferation, respectively. These data suggest a major role for iron in pulmonary vascular homeostasis and support the clinical evaluation of iron replacement in patients with pulmonary hypertension.

Depleted iron stores and iron deficiency anemia associated with reduced ferritin and hepcidin and elevated soluble transferrin receptors in a multiethnic group of preschool-age children.

Iron deficiency anemia is prevalent in subgroups of the Canadian population. The objective of this study was to examine iron status and anemia in preschool-age children. Healthy children (n = 430, 2-5 years old, Montreal, Quebec, Canada) were sampled from randomly selected daycares. Anthropometry, demographics, and diet were assessed. Biochemistry included hemoglobin, ferritin, soluble transferrin receptors (sTfR), ferritin index, markers of inflammation (C-reactive protein, interleukin 6 (IL-6), and tumour necrosis factor alpha (TNFα)), and hepcidin. Iron deficiency and anemia cutoffs conformed to the World Health Organization criteria. Differences among categories were tested using mixed-model ANOVA or χ(2) tests. Children were 3.8 ± 1.0 years of age, with a body mass index z score of 0.48 ± 0.97, and 51% were white. Adjusted intakes of iron indicated <1% were at risk for deficiency. Hemoglobin was higher in white children, whereas ferritin was higher with greater age and female sex. Inflammatory markers and hepcidin did not vary with any demographic variable. The prevalence of iron deficiency was 16.5% (95% confidence interval (CI), 13.0-20.0). Three percent (95% CI, 1.4-4.6) of children had iron deficiency anemia and 12.8% (95% CI, 9.6-16.0) had unexplained anemia. Children with iron deficiency, with and without anemia, had lower plasma ferritin and hepcidin but higher sTfR, ferritin index, and IL-6, whereas those with unexplained anemia had elevated TNFα. We conclude that iron deficiency anemia is not very common in young children in Montreal. While iron deficiency without anemia is more common than iron deficiency with anemia, the correspondingly reduced circulating hepcidin would have enabled heightened absorption of dietary iron in support of erythropoiesis.

Associations between dietary iron and zinc intakes, and between biochemical iron and zinc status in women.

Iron and zinc are found in similar foods and absorption of both may be affected by food compounds, thus biochemical iron and zinc status may be related. This cross-sectional study aimed to: (1) describe dietary intakes and biochemical status of iron and zinc; (2) investigate associations between dietary iron and zinc intakes; and (3) investigate associations between biochemical iron and zinc status in a sample of premenopausal women aged 18–50 years who were recruited in Melbourne and Sydney, Australia. Usual dietary intakes were assessed using a 154-item food frequency questionnaire (n = 379). Iron status was assessed using serum ferritin and hemoglobin, zinc status using serum zinc (standardized to 08:00 collection), and presence of infection/inflammation using C-reactive protein (n = 326). Associations were explored using multiple regression and logistic regression. Mean (SD) iron and zinc intakes were 10.5 (3.5) mg/day and 9.3 (3.8) mg/day, respectively. Median (interquartile range) serum ferritin was 22 (12–38) μg/L and mean serum zinc concentrations (SD) were 12.6 (1.7) μmol/L in fasting samples and 11.8 (2.0) μmol/L in nonfasting samples. For each 1 mg/day increase in dietary iron intake, zinc intake increased by 0.4 mg/day. Each 1 μmol/L increase in serum zinc corresponded to a 6% increase in serum ferritin, however women with low serum zinc concentration (AM fasting < 10.7 μmol/L; AM nonfasting < 10.1 μmol/L) were not at increased risk of depleted iron stores (serum ferritin <15 μg/L; p = 0.340). Positive associations were observed between dietary iron and zinc intakes, and between iron and zinc status, however interpreting serum ferritin concentrations was not a useful proxy for estimating the likelihood of low serum zinc concentrations and women with depleted iron stores were not at increased risk of impaired zinc status in this cohort.

Relationship Between being Overweight and Iron Deficiency in Adolescents

Being overweight has been considered to be a risk factor of iron deficiency (ID). The objective of this study was to examine the relationship between being overweight and body iron status among Taiwanese adolescents. A total of 2099 adolescents (1327 female) aged 12-19years from four middle schools and one college in southern Taiwan participated in this study. Data on sex, age, body weight, height, hemoglobin concentration, plasma ferritin (PF), and serum iron (SI) levels were collected. According to the age- and sex-specific body mass index (BMI) percentiles, the participants were divided into four weight groups: underweight (<5(th) percentile), normal weight (5-84(th) percentile), overweight (85-94(th) percentile), and obese (≥95(th) percentile). A multivariate logistic regression model was used to estimate the odds ratio (OR) and the 95% confidence interval (CI) for each factor. The correlation coefficients of linear regression were positive for BMI-hemoglobin and BMI-PF, but negative for BMI-SI. Compared with the normal-weight group, the obese group had a lower risk of PF level <15μg/L with an OR (95% CI) of 0.51 (0.30-0.87) but a higher risk of SI <60μg/dL with an OR (95% CI) of 1.78 (1.34-2.37). The percentages of low PF declined as BMI increased, but the percentages of low SI rose, from underweight to obesity groups. The relationship between being overweight and depleted iron store depends on which indicator is used to define the iron deficiency. Being overweight or obese would not be a risk factor of ID in adolescents, if ID were defined by PF rather than SI level.

Prevalence and determinants of declining versus stable hemoglobin levels in whole blood donors.

A too short recovery time after blood donation results in a gradual depletion of iron stores and a subsequent decline in hemoglobin (Hb) levels over time. This decline in Hb levels may depend on individual, unobserved characteristics of the donor. We used a data set of 5388 Dutch blood donors from the Donor InSight study. The statistical analysis is based on a Bayesian growth mixture model, which assumes that each donor belongs to one of several groups. Each group implies a different Hb trajectory, and donors with similar longitudinal trajectories belong to the same group. Analyses were performed for male and female donors separately. For both sexes the model identified four groups of donors. Stable Hb trajectories were found among 14% of male donors and 15% of female donors; declining Hb trajectories were observed in the remaining groups of donors. The percentage of donor deferrals differed strongly between groups. The model can be used to predict to which group a donor belongs, and this prediction can be updated after each donation. This is of high practical importance because early identification of donors with declining Hb levels could help to tailor donation intervals and to prevent iron deficiency and donor deferrals.

Monitoring recovery from iron deficiency using total hemoglobin mass.

Using hemoglobin concentration ([Hb]) to diagnose borderline iron deficiency and monitor the progress of its treatment is difficult because of the confounding effects of plasma volume. Because hemoglobin mass (Hbmass) is not affected by plasma volume, it may be a more sensitive parameter. The aim of this study was to monitor Hbmass, iron storage, and maximal oxygen consumption (V˙O2max) during and after oral iron therapy in subjects with severe and moderate iron deficiency. Three groups of female recreational athletes were monitored for at least 22 wk, as follows: 1) severe iron deficiency group (SID) (n = 8; ferritin, ≤12 ng·mL), 2) moderate iron deficiency group (MID) (n = 14; ferritin, ≤25 ng·mL), and 3) control group (n = 8; ferritin, >25 ng·mL). Hbmass and iron status were determined before, during, and up to 12 wk after at least 10 wk of oral iron supplementation. In total, five V˙O2max tests were performed before, during, and after the supplementation period. Hbmass increased markedly in the SID group (15.6% ± 11.0%, P < 0.001) and slightly in the MID group (2.2% ± 3.7%, P < 0.05) by the end of the supplementation period and remained at this level for the following 12 wk. [Hb] and Hbmass were similarly affected, but Hbmass was more closely related to mean corpuscular volume and mean corpuscular hemoglobin than [Hb]. The SID group incorporated 534 ± 127 mg of iron into ferritin and hemoglobin, whereas the MID group incorporated 282 ± 68 mg of iron. V˙O2max increased only in the SID group by 0.20 ± 0.18 L·min (P < 0.05) and was closely related to Hbmass (P < 0.01). Hbmass is a sensitive tool for monitoring recovery from iron deficiency anemia and assessing the effectiveness of iron supplementation in individuals with severe or moderate iron deficiency.

Genetic Hemoglobin Disorders Rather Than Iron Deficiency Are a Major Predictor of Hemoglobin Concentration in Women of Reproductive Age in Rural Prey Veng, Cambodia ,

Anemia is common in Cambodian women. Potential causes include micronutrient deficiencies, genetic hemoglobin disorders, inflammation, and disease. We aimed to investigate factors associated with anemia (low hemoglobin concentration) in rural Cambodian women (18-45 y) and to investigate the relations between hemoglobin disorders and other iron biomarkers. Blood samples were obtained from 450 women. A complete blood count was conducted, and serum and plasma were analyzed for ferritin, soluble transferrin receptor (sTfR), folate, vitamin B-12, retinol binding protein (RBP), C-reactive protein (CRP), and α1 acid glycoprotein (AGP). Hemoglobin electrophoresis and multiplex polymerase chain reaction were used to determine the prevalence and type of genetic hemoglobin disorders. Overall, 54% of women had a genetic hemoglobin disorder, which included 25 different genotypes (most commonly, hemoglobin E variants and α(3.7)-thalassemia). Of the 420 nonpregnant women, 29.5% had anemia (hemoglobin <120 g/L), 2% had depleted iron stores (ferritin <15 μg/L), 19% had tissue iron deficiency (sTfR >8.3 mg/L), <3% had folate deficiency (<3 μg/L), and 1% had vitamin B-12 deficiency (<150 pmol/L). Prevalences of iron deficiency anemia (IDA) were 14.2% and 1.5% in those with and without hemoglobin disorders, respectively. There was no biochemical evidence of vitamin A deficiency (RBP <0.7 μmol/L). Acute and chronic inflammation were prevalent among 8% (CRP >5 mg/L) and 26% (AGP >1 g/L) of nonpregnant women, respectively. By using an adjusted linear regression model, the strongest predictors of hemoglobin concentration were hemoglobin E homozygous disorder and pregnancy status. Other predictors were 2 other heterozygous traits (hemoglobin E and Constant Spring), parity, RBP, log ferritin, and vitamin B-12. Multiple biomarkers for anemia and iron deficiency were significantly influenced by the presence of hemoglobin disorders, hence reducing their diagnostic sensitivity. Further investigation of the unexpectedly low prevalence of IDA in Cambodian women is warranted.

A Rare Case of Congenital Atransferrinemia: International Collaboration for Genetic Diagnosis

Congenital atransferrinemia is an extremely rare hematologic disease caused by transferrin deficiency, and characterized by microcytic hypochromic anemia with iron overload, and that can be fatal if left untreated. The prevalence is unknown. To date, there have been 16 reported cases from 14 families, with few cases confirmed genetically. Here, we report a new case from the Middle East that was diagnosed on clinical ground, and then confirmed by genetic testing through international collaboration.M.T is a 32 months old Egyptian boy, 2nd child of a consanguineous couple, with a healthy 5.5 years older sister. He was born at full term by SVD, suffered physiological jaundice as a newborn. He also had Talipes equinovarus and hypospadias.He was first brought to medical attention at a local hospital at the age of 8 months because of a febrile illness, when he was accidentally discovered to be very pale with Hb of 4.8 g/dl. He received packed RBC transfusion followed by oral iron therapy for 2 weeks, and then another assessment revealed Hb 6.9 g/dl, so he received another transfusion, and then referred to the University Hospital for further assessment.Examined at the age of 20 months, he had marked pallor, tachycardia, and mild hepatosplenomegaly, otherwise the child was normal with average anthropometric measurements.CBC revealed severe microcytic hypochromic anemia (Hb 4.8, MCV 54 fl, MCH 18 pg), MCHC 30 g/dl). Hb electrophoresis: normal Screening for Alfa and Beta thalassemia: normal wild type. Iron profile revealed hypoferremia (Serum iron: 6 ug/dl), TIBC: below assay range, and high serum ferritin: 669 ng/ml. Based on these results, atransferrinemia was suspected, so he was tested for serum transferrin, and reported as very low (8 mg/dl). Bone marrow aspirate was normocellular for age, showing normal granulopoiesis, normoblastic erythropoiesis, and normal megakaryopoiesis, no evidence of dysplasia or abnormal or malignant cells. Prussian blue stain showed depleted iron stores. Serum lead, bilirubin, liver and kidney function tests were normalBoth parents had normal blood picture and iron profile. Human apotransferrin was not available in Egypt, so, plasma transfusion was instituted every 2-4 weeks, through which regimen he is maintaining Hb level between 7-12 gm/dl.As molecular diagnosis for that very rare disease was not feasible in Egypt, after parental consent, blood samples from patient and both parents were sent to Dr. von Haunersches Kinderspital, Munich, and a novel transferrin genemutation was detected by NGS(TF, NM_001063.3, c.1247A>G, p.Y416C) that is currently being validated by Sanger sequencing.To the best of our knowledge, this is the first atransferrinemia report from the Middle East, where prevalence of thalassaemia and iron deficiency anemia is high. However, this rare anemia case underlines the importance of considering rare hereditary disorders like atransferrinemia as the cause for unexplained hypochromic microcytic anemia associated with iron overload, in order to initiate appropriate treatment and avoid iron overload related complications. DisclosuresNo relevant conflicts of interest to declare.