Including Iron Status Research Articles

A study of effect of iron deficiency anemia on glycosylated hemoglobin in non-diabetic patients

Background: Diabetes mellitus is a rapidly increasing global health concern, having a substantial impact on morbidity and mortality. Glycated hemoglobin (HbA1c) is the primary measure of diabetes control, reflecting glycemic levels over the past 3 months. However, hemoglobin (Hb) abnormalities, such as those seen in iron deficiency anemia (IDA), can theoretically affect HbA1c levels. IDA, affecting over 30% of the global population, results from inadequate iron intake, hemorrhage, or poor iron absorption, leading to reduced Hb production. This study aims to evaluate the impact of IDA on HbA1c levels in non-diabetic patients, providing insights into accurate HbA1c interpretation in anemic patients. Aims and Objectives: The study aimed to determine the impact of IDA on HbA1c levels in non-diabetic individuals. Materials and Methods: This cross-sectional study was conducted over 6 months at Trichy SRM Medical College Hospital and Research Center. There were a total of 100 IDA patients and 100 age- and sex-matched healthy controls. Hb levels below 10 g/dL with a microcytic image suggestive of iron deficiency, postprandial blood sugar (PPBS) levels below 140 mg/dL following an oral glucose tolerance test (OGTT), and fasting blood sugar (FBS) levels below 100 mg/dL were the inclusion criteria. Exclusion criteria included Hb levels above 10 g/dL, altered FBS or PPBS values post-OGTT, diagnosed Type 2 diabetes mellitus, individuals younger than 18 years, and those with conditions such as hemoglobinopathies, hemolytic anemia, hypothyroidism, pregnancy, or abnormal renal function tests. Ethical approval and informed consent were obtained. Data collection included demographics, medical history, and laboratory investigations. Statistical analysis was performed using SPSS version 26, with t-tests, mean, and standard deviation (SD) for association analysis, and Chi-square tests for sex comparisons. Correlations were assessed through t-test. The significance level was kept at 0.05. Results: The study confirmed that both groups met the inclusion criteria for non-diabetic status. The control group exhibited normal Hb levels, whereas the study group had Hb levels indicative of IDA. General and systemic examination findings were normal in both groups. Significant differences were observed across all measured parameters, with Hb levels, serum ferritin, mean corpuscular volume, mean corpuscular Hb, mean corpuscular Hb concentration, and red cell distribution width significantly lower in the study group. HbA1c levels were significantly elevated in the study group compared to the control group (5.87 ± 1.25 vs. 4.97 ± 1.59, P < 0.001), supporting the hypothesis that IDA is associated with elevated HbA1c levels in non-diabetic patients. Conclusion: The study’s findings align with previous research indicating that IDA leads to elevated HbA1c levels. The prolonged erythrocyte survival and altered Hb glycation processes in IDA are likely contributors to this elevation. These results emphasize the need to consider anemia status when interpreting HbA1c values to avoid misdiagnosis and inappropriate management of diabetes. Clinicians should ensure comprehensive evaluations, including iron status assessments when encountering unexpectedly high HbA1c levels in non-diabetic individuals.

Micronutrients and Nutrition Status of School-Aged Children in Indonesia.

Micronutrient deficiencies (MNDs) in school-aged children are still a major health problem in Indonesia. This study was designed to examine the status of micronutrients and their relationship to the nutritional status of children aged 5-12 years since an up-to-date database on the micronutrient status of children aged 5-12 years is needed. Data from the 2018 Indonesian Basic Health Research (Riskesdas) were used in this study, with 2456 subjects for analysis. Micronutrient analysis was carried out, including iron status (ferritin, C reactive protein (CRP)), levels of zinc, vitamin D, calcium, and vitamin A (retinol) in school-aged children (5-12 years). The ELISA measurement was applied to measure CRP, ferritin, and vitamin D. Zinc levels were analysed with atomic absorbance spectroscopy (AAS). Moreover, high-performance liquid chromatography (HPLC) was applied to calculate vitamin A. In addition, stunting and thinness data were also obtained from the Riskesdas study. The results showed that the prevalence of stunting and thinness in school-aged children was 11.4% and 9.2%, respectively, showing that the stunting prevalence in the city was lower than in the village (4.5% vs. 6.9%, P = 0.000, respectively). In addition, the prevalence of MNDs in Indonesian children was 13.4%, 19.7%, 4.2%, 3%, and 12.7% for ferritin, zinc, calcium, vitamin A, and vitamin D, respectively. The mean serum level of vitamin A and zinc was significantly lower in stunted children compared to normal school children (P = 0.010 and P = 0.014). The serum concentration of vitamin D was significantly lower in overweight children compared to thin and normal children (P = 0.000). Serum values of ferritin, zinc, and vitamin A were significantly higher in overweight children compared to thin and normal children (P = 0.000). A poor correlation was observed between the z-score of height-for-age (HAZ) and the levels of zinc (r = 0.089, P = 0.000), vitamin A (r = 0.105, P = 0.000), and vitamin D (-0.073, P = 0.000). In addition, very weak correlations between z-scores of body mass index-for-age (BAZ) and the serum concentrations of ferritin (0.091, P = 0.000), zinc (r = 0.115, P = 0.000), vitamin A (r = 0.137, P = 0.000), and vitamin D (r = -0.112, P = 0.000) were also seen. In conclusion, school-aged children in Indonesia experienced stunting, thinness, and micronutrient deficiency. Furthermore, stunting and thinness were also related to micronutrient deficiencies.

Iron supplementation in pregnant Danish women revisited: Effects on prepartum and postpartum iron deficiency, anemia, serum erythropoietin; including iron status, erythropoietin and anthropometrics in newborns. A randomized, placebo-controlled study.

To assess effects of iron supplementation, 66 mg elemental iron daily as ferrous fumarate, on iron status markers during normal pregnancies. Randomized, double-blind, placebo-controlled study of 119 women (62 iron-, 57 placebo -treated) and their newborns. Hemoglobin (Hb), serum (S)-ferritin, S-transferrin saturation percentage (TSAT) and S-erythropoietin (S-EPO) were measured at 14-18, 24-27 weeks of gestation, prepartum, 1 and 8 weeks postpartum. From 24-27 weeks gestation to 8 weeks postpartum, the iron group had higher Hb, S-ferritin and TSAT than the placebo group; prepartum, 11% had iron deficiency (ID) and 0% iron deficiency anemia (IDA) in the iron group, vs 60% and 18% in the placebo group; 8 weeks postpartum 1.6% in the iron group had ID and 1.6% IDA vs 14% and 7% in the placebo group. S-EPO levels in the iron group were lower than in the placebo group (p < 0.001). Mothers prepartum S-EPO values were correlated to newborns cord S-EPO values (p < 0.001). Newborns to iron treated mothers had higher cord S-ferritin levels than those to placebo treated mothers (p = 0.02). Newborn girls had higher cord S-ferritin levels than boys (p < 0.01). There was no impact of iron supplementation on the length of gestation, placental weight, or newborns birth weight. Birth weight was correlated only with mothers' body weight, length of gestation and placental weight. Iron supplementation had a "positive" impact on iron status and Hb both during pregnancy and postpartum, with a low frequency of ID/IDA and also a "positive" influence on newborns iron status.

Nutritional and health status of adult Syrian refugees in the early years of asylum in Germany: a cross-sectional pilot study

BackgroundMigration is usually accompanied by changes in the social, cultural, and religious environment, socioeconomic status, and housing conditions, all of which affect nutritional health. In a cross-sectional study, we assessed the dietary intake as well as nutritional and health situation in a population of Syrian refugees who have resided in Germany for at least six months up to four years since 2015. The primary aim of this pilot study was to evaluate the nutritional and health status in comparison to reference values.MethodsBetween December 2018 and March 2020, 114 adult Syrian refugees were included in the study. The subjects filled out questionnaires on sociodemographic variables, exercise, and nutrition behavior (three-day nutrition record). After a fasting blood draw, the subjects were examined for anthropometric parameters (height, weight, body mass index, waist circumference, waist-hip ratio, and body composition via a bioelectrical impedance analyzer). Various blood markers including iron status, hematological parameters, Vitamin D status, lipid metabolism, glucose metabolism, and total homocysteine (tHcy) were measured.ResultsAbout half of the participants (71 male, 43 female) had lived in Germany for less than three years. Over 60% of men and 30% of women were overweight (BMI 25–30 kg/m2) or obese (BMI > 30 kg/m2), while 79% of men and 74% of women observed an elevated body fat mass. The evaluation of the three-day nutrition records revealed an unfavorable supply situation for numerous critical nutrients. More than half of the women (53.5%) had depleted iron stores (serum ferritin < 15 µg/l). The 25-OH-Vitamin D blood levels showed a high prevalence of Vitamin D insufficiency (25–49.9 nmol/l: 38% of men and 21% of women) and deficiency (< 25 nmol/l: 44% of men and 70% of women). 83% of men and 67% of women showed tHcy levels in plasma > 10 nmol/l. Fasting insulin levels and the HOMA-IR index indicate a risk for insulin resistance. Hyperlipidemia was prevalent, especially in males with 24% showing hypertriglyceridemia (> 150 mg/dl) and LDL-hypercholesterolemia (> 130 mg/dl).ConclusionsThe nutritional and health status of the cohort of Syrian refugees in Germany examined in this study is unsatisfactory, and many of the investigated refugees are at risk for developing cardiovascular disease and type 2 diabetes mellitus. Further studies are required to investigate the nutritional and health situation of refugees. This is obligatory to find ways to avoid malnutrition with all its associated health, sociodemographic, and economic consequences.

Altered Cellular Sedimentation during Apheresis Impacts Outcomes of Peripheral Blood Stem Cell Collection Efficiency in Patients with Sickle Cell Disease

Recent reports have demonstrated the potential for gene therapy as a therapeutic option to achieve a durable cure in patients with sickle cell disease (SCD). However, for these emerging cell therapies, relatively large numbers of peripheral blood hematopoietic stem cells (PB HSCs) are required to generate a therapeutic dose. Outcomes of stem cell collections in patients with SCD are highly variable, at times yielding far fewer numbers of HSCs in the product than predicted by the number of PB CD34+ cells. While the CXCR4 antagonist plerixafor has emerged as a safe and reliable drug to mobilize CD34+ cells in patients with SCD, collection failures continue to occur requiring additional cycles or failure to generate a gene therapy product. We sought to understand the mechanics affecting stem cell sedimentation in real time and posited that SCD disease associated changes to red cells results in altered HSC sedimentation during apheresis, negatively impacting collection. Methods Autologous PB stem cell collections were performed in patients with SCD following mobilization with 240ug/kg plerixafor. To uncover the mechanisms impacting apheresis efficiency for collecting PB HSCs, we devised a method to interrogate the sedimentation of cells in peripheral blood in real time, by interrupting the return collection circuit line. Cellular composition analyses of the collecting interfaces were performed including CD34+ enumeration by flow cytometry, CBC and differential, reticulocyte counts, and surface CD47 expression of red blood cells (RBCs). Results Patients were mobilized with 240ug/kg of plerixafor up to 6 hours before apheresis collection. We collected fewer cells than predicted (3.78 million cells/kg) in these patients with an overall average apheresis collection efficiency of 38%, and a strikingly wide range of 2%-107%. We determined that the lower collection efficiency outcomes were primarily derived when using standard apheresis interface settings. The pre-apheresis PB CD34+ counts were less predictive of total CD34+ cells collected (p=0.012) in patients with SCD (r2=0.2557, p=0.0023) when compared to historical control patients without SCD (r2=0.7638, p<0.0001). Real time measurement of cell counts at standard (Hematocrit 3%, S) and deep (Hematocrit 5%, D) collecting interfaces of the apheresis machine showed a significant decrease in lymphocytes (p=0.0146), increase in monocytes (p=0.0496), and increase enrichment in CD34+ cells at the D interface (Panel A). Enrichment of CD34+ cells correlated with monocyte enrichment and (n=21, r2=0.6706, p<0.0001) and an increased fold change in CD34+ cells between the S and D interfaces correlated with higher PB reticulocyte percentage (r2=0.5295, p=0.0111). Further analysis of the individual collection interfaces revealed that most RBCs were HbS containing despite a PB HbS concentration <30%, consistent with an enrichment for shorter lived sickle red cells. CD47 expression has been previously reported in higher concentrations on the surface of younger RBCs during erythropoiesis. Surface expression of CD47 was found to be significantly higher at both the S and D interfaces compared to the PB of patients, indicating that the accumulation of a younger population of RBCs at the collecting interfaces. As microcytic RBCs have been associated with poor collection efficiencies, the SCD red cell hemoglobin concentration in the PB was used as a marker for size and a significant correlation was determined (r2=0.6086, p=0.0001). Patients with SCD can mobilize PB HSC in response to plerixafor but demonstrate specific characteristics that impede the collection of stem cells. During apheresis, CD34+ stem cells sediment at a deeper hematocrit interface in the buffy coat as a result of displacement by the younger patient-derived population of RBCs. The relative shift in erythrocyte sedimentation requires a corresponding alteration in collection strategies to improve the collection efficiency. In addition to red cell age, other factors that affect red cell buoyancy including iron status or additional globin gene mutations negatively impact apheresis stem cell collections. Full assessment of red cell parameters can identify patients that are at risk for poor stem cell collection outcomes. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Iron status and lipopolysaccharide regulate Ndfip1 by activation of nuclear factor-kappa B

Nedd4 family interacting protein 1 (Ndfip1) is an adaptor protein for the Nedd4 family of ubiquitin ligases that target proteins for degradation. Recent studies confirmed the role of Ndfip1 as a regulator of iron metabolism and pointed out that Ndfip1 was involved in iron homeostasis by regulating the degradation of iron importer divalent metal transporter 1 (DMT1). However, little is known about how Ndfip1 is regulated. The aim of this article was to investigate the regulation of Ndfip1 levels and the possible mechanisms. In this study, we investigated the effect of various stimuli, including iron status and lipopolysaccharide (LPS) on Ndfip1 expression in MES23.5 dopaminergic cell lines. Results showed that Ndfip1 expression in these cells was enhanced by ferrous iron overload, but not ferric iron overload, and decreased after iron deprivation by deferoxamine. In addition, LPS could significantly increase the expression of Ndfip1. Furthermore, we demonstrated that the regulation of Ndfip1 expression by these various stimuli was achieving by activation of nuclear factor-kappa B. We speculate that iron status and LPS may contribute to the changes of Ndfip1 expression by activation of nuclear factor-kappa B.

Correlation ofhemochromatosisgene mutations and cardiovascular disease in hemodialysis patients

BACKGROUND AND OBJECTIVESCardiovascular disease (CVD) is a major cause of death in hemodialysis (HD) patients. Hemochromatosis (HFE) gene mutations are reported to be associated with CVD. The present study aims to investigate the association of HFE gene polymorphism with CVD in HD patients.DESIGN AND SETTINGSCross-sectional case-control.METHODSC282Y/H63D mutations of HFE gene were evaluated in 560 HD patients and 480 healthy controls from 4 HD centers in North China. The results obtained from this evaluation process were correlated with biochemical parameters including iron status (serum iron, ferritin, and transferrin concentration), cardiovascular disease, and inflammation marker CRP, IL-6, TNF-α.RESULTSNo C282Y mutations were detected in HD patients or healthy controls in this study. The genotype of H63D heterozygous mutation was similar in HD patients with CVD, HD patients without CVD, and controls. H63D homozygous mutation was 7.4% (19/257), 3.1% (9/303), and 1.0% (5/480) for the 3 groups, respectively. Compound heterozygosity was not found in this study. The relative risk for CVD in HD patients with H63D homozygous mutation was 2.59 (95% CI: 1.15–5.84). H63D homozygous mutation had significantly higher serum ferritin concentrations compared with wild-type individuals. Moreover, HD patients had significantly higher levels of inflammatory biomarkers such as CRP, IL-6, and TNF-α. The multivariate logistic regression analysis revealed that H63D mutation instead of ferritin level was an independent risk factor of CVD for HD patients.CONCLUSIONSOur study demonstrates for the first time that there was an association between H63D homozygous mutations and CVD in HD patients. Elevated serum CRP, IL-6, and TNF-α levels were also related to CVD in HD patients.

Iron metabolism in hepcidin1 knockout mice in response to phenylhydrazine-induced hemolysis

Hepcidin, an iron regulatory peptide, plays a central role in the maintenance of systemic iron homeostasis by inducing the internalization and degradation of the iron exporter, ferroportin. Hepcidin expression in the liver is regulated in response to several stimuli including iron status, erythropoietic activity, hypoxia and inflammation. Hepcidin expression has been shown to be reduced in phenylhydrazine-treated mice, a mouse model of acute hemolysis. In this mouse model, hepcidin suppression was associated with increased expression of molecules involved in iron transport and recycling. The present study aims to explore whether the response to phenylhydrazine treatment is affected by hepcidin deficiency and/or the subsequently altered iron metabolism. Hepcidin1 knockout (Hamp(-/-)) and wild type mice were treated with phenylhydrazine or saline and parameters of iron homeostasis were determined 3 days after the treatment. In wild type mice, phenylhydrazine administration resulted in significantly reduced serum iron, increased tissue non-heme iron levels and suppressed hepcidin expression. The treatment was also associated with increases in membrane ferroportin protein levels and spleen heme oxygenase 1 mRNA expression. In addition, trends toward increased mRNA expression of duodenal iron transporters were also observed. In contrast, serum iron and tissue non-heme iron levels in Hamp(-/-) mice were unaffected by the treatment. Moreover, the effects of phenylhydrazine on the expression of ferroportin and duodenal iron transporters were not observed in Hamp(-/-) mice. Interestingly, mRNA levels of molecules involved in splenic heme uptake and degradation were significantly induced by Hamp disruption. In summary, our study demonstrates that the response to phenylhydrazine-induced hemolysis differs between wild type and Hamp(-/-) mice. This observation may be caused by the absence of hepcidin per se or the altered iron homeostasis induced by the lack of hepcidin in these mice.

Influence of inflammatory disorders and infection on iron absorption and efficacy of iron-fortified foods.

The provision of iron- fortified foods is a common strategy to prevent iron deficiency; however, ensuring adequate iron absorption is a challenge. Iron bioavailability depends on the choice of iron compound, the presence enhancers and inhibitors of absorption in the food matrix, and the physiological state of the consumer, including iron status, other nutritional deficiencies and inflammatory disorders. Inflammation associated with infections and inflammatory disorders would be expected to decrease iron absorption and reduce the efficacy of iron- fortified foods. The decreased absorption is due to an increase in circulating hepcidin in response to inflammatory cytokines. Hepcidin degrades ferroportin and blocks the passage of iron from the intestinal cell to the plasma. This is the innate immune response to infections and aims to restrict pathogen growth by restricting iron supply. Stable isotope studies have reported women and children with chronic malaria parasitemia or febrile malaria to have increased inflammatory cytokines, increased hepcidin and much decreased iron absorption. No studies have specifically investigated the efficacy of iron- fortified foods in the absence and presence of infections. In contrast, inflammation and increased hepcidin associated with adiposity in overweight have been linked to both lower iron absorption and the decreased efficacy of iron- fortified foods.

Anemia after gastrectomy for early gastric cancer: Long-term follow-up observational study

To identify the incidence and etiology of anemia after gastrectomy in patients with long-term follow-up after gastrectomy for early gastric cancer. The medical records of those patients with early gastric adenocarcinoma who underwent curative gastrectomy between January 2006 and October 2007 were reviewed. Patients with anemia in the preoperative workup, cancer recurrence, undergoing systemic chemotherapy, with other medical conditions that can cause anemia, or treated during follow up with red cell transfusions or supplements for anemia were excluded. Anemia was defined by World Health Organization criteria (Hb < 12 g/dL in women and < 13 g/dL in men). Iron deficiency was defined as serum ferritin < 20 μg/dL. Vitamin B₁₂ deficiency was defined as serum vitamin B₁₂ < 200 pg/mL. Iron deficiency anemia was defined as anemia with concomitant iron deficiency. Anemia from vitamin B₁₂ deficiency was defined as megaloblastic anemia (mean cell volume > 100 fL) with vitamin B₁₂ deficiency. The profile of anemia over 48 mo of follow-up was analyzed. One hundred sixty-one patients with gastrectomy for early gastric cancer were analyzed. The incidence of anemia was 24.5% at 3 mo after surgery and increased up to 37.1% at 48 mo after surgery. The incidence of iron deficiency anemia increased during the follow up and became the major cause of anemia at 48 mo after surgery. Anemia of chronic disease and megaloblastic anemia were uncommon. The incidence of anemia in female patients was significantly higher than in male patients at 12 (40.0% vs 22.0%, P = 0.033), 24 (45.0% vs 25.0%, P = 0.023), 36 (55.0% vs 28.0%, P = 0.004), and 48 mo (52.0% vs 31.0%, P = 0.022) after surgery. Patients with total gastrectomy showed significantly higher incidence of anemia than patients with subtotal gastrectomy at 48 mo after surgery (60.7% vs 31.3%, P = 0.008). The incidence of iron deficiency was significantly higher in female patients than in male patients at 6 (35.4% vs 13.3%, P = 0.002), 12 (45.8% vs 16.8%, P < 0.001), 18 (52.1% vs 22.3%, P < 0.001), 24 (60.4% vs 20.9%, P < 0.001), 36 (62.5% vs 29.2%, P < 0.001), and 48 mo (66.7% vs 34.7%, P = 0.001) after surgery. Anemia was frequent after gastrectomy for early gastric cancer, with iron deficiency being the major cause. Evaluation for anemia including iron status should be performed after gastrectomy and appropriate iron replacement should be considered.

Iron studies and red cell transfusion in cardiothoracic and orthopaedic surgical patients: a retrospective audit at a tertiary hospital

Preoperative diagnosis and treatment of anaemia are important to minimize adverse postoperative outcomes. This audit reviewed red cell transfusion practice, degree of anaemia, iron deficiency anaemia (IDA) and chronic disease or anaemia of inflammation (AI) in cardiothoracic and orthopaedic surgical patients who had available iron studies. A total of 178 consecutive cardiothoracic and orthopaedic surgical patients with available iron studies were retrospectively reviewed. Of patients, 36·5% had preoperative iron studies. However, 63·2% males and 45·3% females with postoperative iron studies presented with anaemia; 38·5% patients with preoperative iron studies had AI; 21·5% IDA; 23·1% normal. For patients with iron studies requested within the first two postoperative intervals (≤ 5 days and 6 ≤ 10 days) 73·8% and 63·6%, respectively, had AI; few had classical IDA or were normal, and 51·5% patients transfused postsurgery had a discharge Hb ≥ 110 g/l. Restricting the discharge Hb to 90 or 100 g/l may have eliminated postsurgical transfusion in 14·8-42·6% patients. Iron studies were more commonly requested postoperatively despite many being anaemic at admission. A higher proportion of patients with postoperative iron studies had AI, and few had classical IDA or normal iron parameters, suggesting a transient inflammatory effect of surgery. This may mask underlying IDA or normal iron parameters and affect treatment. Preadmission assessment, including iron status, should be emphasized allowing diagnosis and correction of presurgical anaemia with treatment modalities other than red cell transfusion. In the postsurgical setting, consideration of a restrictive transfusion regimen sufficient to alleviate a patient's clinical symptoms would ensure that this valuable resource is appropriately used.

The glycaemic potency of breakfast and cognitive function in school children

The aim of this study was to assess how the glycaemic potency (blood glucose (BG)-raising potential) of breakfast is associated with cognitive function (CF) in school children, taking into account important confounders, including iron status, underlying physiological adaptations and socio-economic status. Sixty children aged 11-14 years were selected on the basis of having breakfast habitually. Their breakfast and any snacks eaten on the morning of the study were recorded. They were categorized into four groups according to the glycaemic index (GI) and glycaemic load (GL) of the breakfast: low-GI, high-GL; high-GI, high-GL; low-GI, low-GL and high-GI, low-GL above or below the median for GI=61 and GL=27. BG levels were measured in finger-prick blood samples immediately before and immediately after the CF tests. A low-GI, high-GL breakfast was associated with better performance on a speed of information processing (P<0.01) and a serial sevens (P<0.001) task 90 min later; a high-GI breakfast with better performance on an immediate word recall task (P<0.01); and a high-GL breakfast with better performance on a Matrices task (P<0.01). GI, GL or both were associated with performance on the majority of the CF tests (4 of 7) used. This study describes the macronutrient composition of breakfast that could have a positive influence on the cognition of school children, proposes the use of both GI and GL to estimate exposure, and discusses future directions in this area of research.

Association between iron status and neurodevelopmental outcomes among VLBW infants

Objective: Our purpose was to evaluate iron status and neurodevelopmental outcomes in infants with and without extrauterine growth restriction (EUGR). Methods: This observational study evaluated 38 medically stable premature infants, with birth weights below 1500 g. Iron status was determined by measuring venous levels of Hb, Fe, and serum ferritin. The infants were divided into EUGR and non-EUGR groups. At a corrected age of 18 months, neurodevelopmental outcomes were checked using the Bayley scales, and body weight, body length, and head circumference were measured. Results: Hb levels at corrected ages of 1 and 3 months and iron at a corrected age of 1 and 9 months were significantly lower in the EUGR group compared with those of the non-EUGR group. There was no significant difference in the MDI score between the groups, but the PDI score at a corrected age of 18 months was significantly lower in the EUGR group. We found a positive correlation between the serum level of Fe at 1 month of age and PDI score at 18 months of age. Head circumference at a corrected age of 18 months did not differ between two groups, although body weight and length were lower in the EUGR group. Conclusions: Developmental outcome in preterm infants at a corrected age of 18 months may be influenced by nutritional factors, including iron status, during their early life.

Iron absorption and metabolism

Intestinal iron absorption is an essential physiological process that is regulated by the liver-derived peptide hepcidin. This review will describe recent advances in hepcidin biology and enterocyte iron transport. Hepcidin acts as a repressor of iron absorption and its expression in turn reflects a range of systemic cues, including iron status, hypoxia, erythropoiesis and inflammation. These act through proteins on the hepatocyte plasma membrane such as HFE, hemojuvelin and transferrin receptor 2 to alter transcription of the hepcidin gene. Bone morphogenetic protein-SMAD signaling provides a key pathway of hepcidin activation, whereas the membrane-bound serine protease matriptase-2 and the erythroid factor growth differentiation factor 15 have emerged as important negative regulators of hepcidin expression. At the enterocyte itself, the recent demonstration of a chaperone for delivering iron to ferritin and new data on iron release from the hepcidin target ferroportin are helping to define the pathway of iron movement across the intestinal epithelium. Disturbances in the hepcidin regulatory pathway underlie a range of iron metabolism disorders, from iron deficiency to iron loading, and there is considerable promise that the exciting recent advances in understanding hepcidin action will be translated into improved diagnostic and therapeutic modalities in the near future.

Iron status at 1 and 6 years versus developmental scores at 6 years in a well‐nourished affluent population

To examine the association between iron status at 1 and 6 years with development at 6 years. In a longitudinal study of children (n = 77), iron status was measured at 1 and 6 years and the Icelandic Developmental Inventory, which evaluates children's motor and verbal development, was filled in by mothers near the children's sixth birthday. Children, iron-deficient at 1 year (n = 10), had lower fine motor development scores at 6 years than non-iron-deficient (n = 56) (46.7 +/- 4.1 vs. 49.3 +/- 2.0; p = 0.011). Fine motor scores were also lower in children with depleted iron stores at 1 year (n = 26) than non-iron-depleted children (n = 40) (48.0 +/- 3.3 vs. 49.5 +/- 1.8; p = 0.045). Multiple regression analyses, with iron status indices at 6 years, showed that mean corpuscular volume along with male gender predicted significantly positively for expression (adj. R(2)= 0.15; p = 0.018; n = 73), while regression analyses, including iron status at 1 and 6 years, showed that haemoglobin at 6 years was positively associated with gross motor (adj. R(2)= 0.05; p = 0.038; n = 63). In an affluent society, iron deficiency and depleted iron stores at 1 year may contribute to worse fine motor developmental scores at 6 years, while low mean corpuscular volume and haemoglobin at 6 years might affect subsequent expression and gross motor scores negatively.

Iron therapy, advanced oxidation protein products, and carotid artery intima-media thickness in end-stage renal disease.

Increased common carotid artery intima-media thickness (CCA-IMT) is a marker of early atherosclerosis. Low-grade inflammation is associated with the pathogenesis of atherosclerosis. Low-grade inflammation and increased CCA-IMT are observed in end-stage renal disease (ESRD). Oxidative stress is involved in uremia-related inflammation. Advanced oxidation protein products (AOPP) are markers of oxidant-mediated protein damage in ESRD. Intravenous iron given to patients on hemodialysis (HD) might induce oxidative stress. We investigated the relationships between AOPP, iron therapy, and CCA-IMT in stable HD patients. Plasma AOPP and blood chemistry, including iron status, were analyzed in a cohort of 79 ESRD patients on HD. Measurements of CCA-IMT and CCA diameter, as assessed by B-mode ultrasonography, were obtained in 60 patients. AOPP levels were elevated in ESRD patients, and in univariate (r=0.42, P<0.0001) and multivariate analyses (r=0.38, P<0.001), they correlated with serum ferritin and with the intravenous iron dose received during the 12 months preceding the study (ferritin, P<0001; AOPP, P<0.01). Univariate and multivariate analyses identified the AOPP concentration as being significantly associated with CCA-IMT (P=0.0197) and CCA wall-to-lumen ratio (r=0.560, P<0.0001). Independently of AOPP concentration, cumulative iron dose was positively related to CCA-IMT (P=0.015) in patients <60 years. In ESRD patients, CCA-IMT and CCA wall-to-lumen ratio were associated with plasma AOPP, serum ferritin, and the annual intravenous iron dose administered. These findings support the concept of a role of oxidative stress in the early atherosclerosis of ESRD patients, which may be increased by the usually recommended doses of intravenous iron.

Serum ferritin: a predictor of early spontaneous preterm delivery

To identify biochemical indices for iron and protein nutriture as well as acute-phase reactants as predictors of preterm delivery. In this nested case-control study, serum samples were obtained at about 24 weeks' gestation from 94 indigent multiparas. These cases were defined based on having a spontaneous delivery of 32 weeks or less (n = 31) with two control groups, one delivering spontaneously at 33-36 weeks (n = 32) and the other delivering spontaneously at 37 weeks or more (n = 31). The concentrations of iron, ferritin, transferrin, transferrin saturation, and transferrin receptor were measured as indices of iron status. The concentrations of acute-phase reactants, including C-reactive protein, alpha-2-macroglobulin, beta-2-microglobulin and ceruloplasmin, were also measured, along with albumin, prealbumin, retinol-binding protein, copper, and zinc. Serum ferritin concentrations were negatively correlated with gestational age at birth (P = .034). For subjects having serum ferritin levels above the median compared with those below, the odds ratio of having an early spontaneous preterm delivery was 2.99 (95% confidence interval 1.13-7.89). The other indices, including iron status and the acute-phase reactants, were not significantly associated with gestational age at birth. Elevated serum ferritin levels during the second trimester are predictive of early spontaneous preterm delivery, possibly because these reflect an acute-phase reaction to subclinical infections that are closely associated with premature delivery.