Overview of Trends in Anemia and Iron Deficiency in the Mexican Population From 1999 to 2018-19.

BACKGROUND: Despite the emergence of diverse programs in Mexico to address anemia and micronutrient deficiencies in disadvantaged groups, progress on reducing their prevalence has stagnated. In Mexico, anemia surveillance at the population level is conducted through the National Health and Nutrition Survey ENSANUT (for its acronym in Spanish). OBJECTIVE: To overview the trends in anemia and iron deficiency (ID) from 1999 to 2018-19 in the Mexican population before COVID-19 pandemic. METHODS: Data from five nationwide surveys in Mexico were used. Where available, data on anemia, ID, and ID anemia (IDA) were extracted from ENSANUTs 1999, 2006, 2012, 2016, and 2018-19 in participants from 1 to 99 years old. Blood sample collection methods were similar across surveys (1999-2018) where capillary drop blood was used to estimate Hb using a HemoCue and serum blood samples to measure ferritin and C-reactive protein concentration. RESULTS: The trend in anemia prevalence shows a U-shape from 1999 to 2018-19 in <60 years old. In older adults (≥60 years), an increasing trend was observed. Anemia declined progressively from 1999 to 2012 but increased from 2016 to 2018-19 in comparison with 2012. In contrast, ID declined from 2006 to 2018-19, mainly in children, while IDA did not change over this period. In older adults, ID prevalence remained constant over time. CONCLUSIONS: The shifting trend in anemia prevalence across ENSANUTs 1999 through 2018-19 did not mimic the decreasing trend of ID over the same period of time. Other noncausal factors seem to play an important role in the variability of hemoglobin measurements.

Plain language titleOverview of Trends in the Prevalence of Anemia and Iron Deficiency in the Mexican Population From 1999 to 2018-19Plain language summaryIn Mexico, anemia surveillance has been monitored through the National Health and Nutrition Survey since 1999. Nonetheless, progress on reducing their prevalence seems to be stagnated despite the emergence of diverse social programs in Mexico to tackle micronutrient deficiencies in children and women. The main cause of anemia in children and women is iron deficiency (ID). Any progress in tackling ID should be reflected in anemia prevalence. To investigate the prevalence trend, we used information about anemia (based on hemoglobin concentration) and ID (based on serum ferritin levels) where available, from 5 nationwide surveys in Mexico among participants from 1 to 99 years old, to discuss some of the potential factors behind anemia and ID trends. From 1999 to 2018-19, we observed an ¨U" shape in the prevalence of anemia in all age groups <60 years old, contrasting with the prevalence of ID, which trend is in decline. No major changes in terms of social programs can explain the trend in anemia. In fact, other nutritional indicators seem to have improved in Mexican children. A major difference in the measurement of anemia and ID is that hemoglobin was measured in situ using drop of capillary blood in HemoCue, a portable photometer, while ferritin was measured in venous blood in the central laboratory. While many external factors might influence the hemoglobin measurement in the field setting, it seems that the technique of finger prick capillary introduces more errors to the measurement of hemoglobin than other techniques (e.g., pool capillary or venous blood using HemoCue). This difference, in turn, affects anemia diagnosis. Since the drop of capillary blood has been widely acceptable, we did not perform any validation of hemoglobin measurement in those past surveys, so we cannot role out the contribution of other factors that affected hemoglobin measurement. Future studies should use venous blood to improve anemia classification; otherwise, validation studies should be carried out to improve hemoglobin measurement when using capillary blood.

Iron-Deficiency Prevalence and Supplementation Practices Among Pregnant Women: A Secondary Data Analysis From a Clinical Trial in Vancouver, Canada.

BACKGROUND: North American public health guidelines recommend supplementation with an iron-containing prenatal multivitamin throughout pregnancy to meet the RDA of 27 mg of elemental iron daily. However, whether supplementation with standard prenatal multivitamins is sufficient to prevent maternal iron deficiency is unclear, as needs increase substantially with advancing gestation. OBJECTIVES: This study aimed to assess iron status in early and late pregnancy among 60 pregnant women receiving 27 mg/day of elemental iron as part of a randomized trial in Vancouver, Canada. METHODS: Study visits were conducted at 8-21 (baseline) and 24-38 (endline) weeks of gestation. Venous blood specimens were collected for a complete blood count and measurement of iron and inflammatory biomarkers. Supplementation with any additional iron (beyond 27 mg/day) was reported by participants (treatment with additional iron is recommended if ferritin is <30 µg/L). Quantile regression was used to explore predictors of endline ferritin concentrations, including ethnicity, education, income, and baseline ferritin measurement. RESULTS: Overall, 60 and 54 women participated in baseline and endline visits, respectively. Rates of probable iron deficiency (ferritin <30 µg/L) at baseline and endline were 17 (28%) and 44 (81%), respectively. Less than half (n = 18; 41%) of participants with probable iron deficiency at endline reported supplementation with additional iron. Ethnicity was the only significant modifier of endline ferritin, with higher concentrations in those of South, East, and Southeast Asian ethnicity compared to those of European ethnicity (ß: 10.4 µg/L; 95% CI: 0.3-20.5). CONCLUSIONS: Pregnant individuals may require additional supplemental iron beyond 27 mg to meet requirements in later pregnancy, given the high rates of iron deficiency observed in this clinical trial, despite consumption meeting 100% of the RDA. This trial was registered at clinicaltrials.gov as NCT04022135.

Efficacy and Safety of Ferrous Bisglycinate and Folinic Acid in the Control of Iron Deficiency in Pregnant Women: A Randomized, Controlled Trial.

Iron deficiency in pregnancy is a major public health problem that causes maternal complications. The objective of this randomized, controlled trial was to examine the bioavailability, efficacy, and safety of oral ferrous bisglycinate plus folinic acid supplementation in pregnant women with iron deficiency. Subjects (12−16 weeks of gestation, n = 120) were randomly allocated to receive oral iron as ferrous bisglycinate (equiv. iron 24 mg) in supplement form with folinic acid and multivitamins (test group, n = 60) or as ferrous fumarate (equiv. iron 66 mg iron, control group, n = 60) after breakfast daily. Iron absorption was assessed by measuring fasted serum iron levels at 1 and 2 h immediately after supplementation. Hematological biomarkers and iron status were assessed before intervention, and at 3 and 6 months. Side effects were monitored throughout the intervention. A significant increase in serum iron was seen in both groups (p < 0.001) during the bioavailability assessment; however, the test group increases were comparatively higher than the control values at each timepoint (p < 0.001). Similarly, both test and control groups demonstrated a statistically significant increases in hemoglobin (Hb) (p < 0.001), erythrocytes (p < 0.001), reticulocytes (p < 0.001), mean corpuscular volume (MCV) (p < 0.001), mean corpuscular hemoglobin (MCH) (p < 0.001), mean corpuscular hemoglobin concentration (MCHC) (p < 0.001), % transferrin saturation (p < 0.001), and ferritin (p < 0.001) at 3 and 6 months after supplementation. However, in all cases, the test group increases were numerically larger than the control group increases at each timepoint. The test intervention was also associated with significantly fewer reports of nausea, abdominal pain, bloating, constipation, or metallic taste (p < 0.001). In conclusion, ferrous bisglycinate with folinic acid as a multivitamin nutraceutical format is comparable to standard ferrous fumarate for the clinical management of iron deficiency during pregnancy, with comparatively better absorption, tolerability, and efficacy and with a lower elemental iron dosage.

Zinc protoporphyrin levels in COVID-19 are indicative of iron deficiency and potential predictor of disease severity.

BACKGROUND: Coronavirus disease (COVID-19) has a severe impact on all aspects of patient care. Among the numerous biomarkers of potential validity for diagnostic and clinical management of COVID-19 are biomarkers at the interface of iron metabolism and inflammation. METHODS: The follow-up study included 54 hospitalized patients with laboratory-confirmed COVID-19 with a moderate and severe/critical form of the disease. Iron deficiency specific biomarkers such as iron, ferritin, transferrin receptor, hepcidin, and zinc protoporphyrin (ZnPP) as well as relevant markers of inflammation were evaluated twice: in the first five days when the patient was admitted to the hospital and during five to 15 days; and their validity to diagnose iron deficiency was further assessed. The regression and Receiver Operating Characteristics (ROC) analyses were performed to evaluate the prognosis and determine the probability for predicting the severity of the disease in the first five days of COVID-19. RESULTS: Based on hemoglobin values, anemia was observed in 21 of 54 patients. Of all iron deficiency anemia-related markers, only ZnPP was significantly elevated (P<0.001) in the anemic group. When patients were grouped according to the severity of disease, slight differences in hemoglobin or other anemia-related parameters could be observed. However, the levels of ZnPP were significantly increased in the severely ill group of patients. The ratio of ZnPP to lymphocyte count (ZnPP/L) had a discrimination power stronger than the neutrophil to lymphocyte count ratio (N/L) to determine disease severity. Additionally, only two markers were independently associated with the severity of COVID-19 in logistic regression analysis; D-dimer (OR (5.606)(95% CI 1.019-30.867)) and ZnPP/L ratio (OR (74.313) (95% CI 1.081-5108.103)). CONCLUSIONS: For the first time ZnPP in COVID-19 patients were reported in this study. Among all iron-related markers tested, ZnPP was the only one that was associated with anemia as based on hemoglobin. The increase in ZnPP might indicate that the underlying cause of anemia in COVID-19 patients is not only due to the inflammation but also of nutritional origin. Additionally, the ZnPP/L ratio might be a valid prognostic marker for the severity of COVID-19.

Characterization of acquired anemia in children by iron metabolism parameters.

Inflammatory states are associated with anemia of chronic disease and acute infection. Hepcidin, a regulator of iron metabolism, is involved in iron pathophysiology during inflammation. We investigated biochemical characteristics in children with anemia from different causes. Four patient groups (n = 38; mean age: 12.44 ± 4.35 years) were studied: (1) inflammatory bowel disease (IBD, 10 patients); (2) iron deficiency anemia (IDA, 12); (3) celiac disease (CD, 8); (4) acute infection (AI, 8). Laboratory measurements were evaluated at diagnosis: blood count, serum iron, transferrin, ferritin, vitamin B12, folic acid, CRP, erythropoietin, hepcidin and soluble transferrin receptor (sTfR). IDA patients had the lowest Hgb (6.9 ± 1.7 g/dL), MCV (63.2 ± 7.2 fL), iron (16.8 ± 13.5 µg/dL), ferritin (4.5 ± 4.5 ng/mL) and hepcidin (3.1 ± 0.8 ng/mL) values, and the highest transferrin and sTfR values. AI patients had the highest ferritin (156.2 ± 124.5 ng/mL), CRP (144.6 ± 94 mg/L) and hepcidin (74.67 ± 12.3 ng/ml) values. Overall, hepcidin levels correlated with CRP and with ferritin (r = 0.83 and 0.85, respectively). Elucidating specific etiology-related biochemical profiles in pediatric patients with anemia from different causes using a combination of laboratory biomarkers, including hepcidin, can help physicians treat the anemia.

Transferrin Saturation/Hepcidin Ratio Discriminates TMPRSS6-Related Iron Refractory Iron Deficiency Anemia from Patients with Multi-Causal Iron Deficiency Anemia.

Pathogenic TMPRSS6 variants impairing matriptase-2 function result in inappropriately high hepcidin levels relative to body iron status, leading to iron refractory iron deficiency anemia (IRIDA). As diagnosing IRIDA can be challenging due to its genotypical and phenotypical heterogeneity, we assessed the transferrin saturation (TSAT)/hepcidin ratio to distinguish IRIDA from multi-causal iron deficiency anemia (IDA). We included 20 IRIDA patients from a registry for rare inherited iron disorders and then enrolled 39 controls with IDA due to other causes. Plasma hepcidin-25 levels were measured by standardized isotope dilution mass spectrometry. IDA controls had not received iron therapy in the last 3 months and C-reactive protein levels were <10.0 mg/L. IRIDA patients had significantly lower TSAT/hepcidin ratios compared to IDA controls, median 0.6%/nM (interquartile range, IQR, 0.4-1.1%/nM) and 16.7%/nM (IQR, 12.0-24.0%/nM), respectively. The area under the curve for the TSAT/hepcidin ratio was 1.000 with 100% sensitivity and specificity (95% confidence intervals 84-100% and 91-100%, respectively) at an optimal cut-off point of 5.6%/nM. The TSAT/hepcidin ratio shows excellent performance in discriminating IRIDA from TMPRSS6-unrelated IDA early in the diagnostic work-up of IDA provided that recent iron therapy and moderate-to-severe inflammation are absent. These observations warrant further exploration in a broader IDA population.

Iron deficiency as promoter of heavy metals-induced acute myeloid leukemia.

Iron deficiency (ID) and iron deficiency anemia (IDA) have many adverse effects on human health. Also, iron deficiency anemia and anemia in general are linked with an increased risk of various cancers, particularly blood cancers. It is known that subjects with IDA as well as smokers have elevated blood levels of toxic divalent cations, particularly cadmium (Cd2+) and lead (Pb2+). Cadmium is a proven carcinogen. Most of the circulating cadmium is bound to transferrin and apart from the target organs of cadmium accumulation, kidney and liver, tissues (cells) which highly express transferrin receptor 1 (TfR1) may also accumulate high levels of circulating cadmium. Density of TfR1, glycoprotein that is expressed on cell surface, is not uniform in bone marrow cells. Namely, megakaryocyte/erythrocyte progenitors and pro-erythroblasts express TfR1 incomparably more than other cell lines within the bone marrow and we hypothesize that the mentioned cell lines will uptake most of the circulating cadmium and lead, and will consequently be most suitable for malignant transformation. In this review, we discuss in detail the mechanisms involved in accumulation of cadmium in particular cell lines of the bone marrow and the consequent occurrence of acute myeloid leukemia (AML).

Hypochromic red cells as predictors of anemia in patients undergoing hemodialysis: an observational retrospective study.

The percentage of hypochromic red blood cells (%HRC) estimates the availability of iron by evaluating the degree of hemoglobinization. We investigated whether %HRC was a predictor of anemia in patients undergoing hemodialysis. We recruited 142 patients undergoing routine hemodialysis between 2017 and 2019. Delta hemoglobin level (ΔHb)1mo-baseline was calculated as the difference between the hemoglobin level at 1 month after study enrollment and that at the time of study enrollment. Development of anemia was defined as hemoglobin level ≤ 15% of baseline. The median %HRC was 3.1%. There was a significant negative correlation between (ΔHb)1mo- baseline and %HRC (r = - 0.63, P < 0.001). The incidence of anemia was significantly higher in patients with %HRC > 3.1% than in those with %HRC ≤ 3.1%. In the multivariate logistic regression analysis, %HRC was significantly related to the development of anemia (odds ratio 2.57, 95% confidence interval [CI] 1.72-3.85, P < 0.001). The best cutoff value for %HRC to predict the development of anemia was 4.3%, with a sensitivity and specificity of 67.74 (95% CI, 54.7-79.1) and 97.50 (95% CI, 91.3- 99.7), respectively. %HRC is an independent predictor of anemia in patients undergoing hemodialysis. %HRC ≤ 4.3% is an early marker to consider changing the anemia treatment.

Iron Deficiency Caused by Intestinal Iron Loss-Novel Candidate Genes for Severe Anemia.

The adult human body contains about 4 g of iron. About 1-2 mg of iron is absorbed every day, and in healthy individuals, the same amount is excreted. We describe a patient who presents with severe iron deficiency anemia with hemoglobin levels below 6 g/dL and ferritin levels below 30 ng/mL. Although red blood cell concentrates and intravenous iron have been substituted every month for years, body iron stores remain depleted. Diagnostics have included several esophago-gastro-duodenoscopies, colonoscopies, MRI of the liver, repetitive bone marrow biopsies, psychological analysis, application of radioactive iron to determine intact erythropoiesis, and measurement of iron excretion in urine and feces. Typically, gastrointestinal bleeding is a major cause of iron loss. Surprisingly, intestinal iron excretion in stool in the patient was repetitively increased, without gastrointestinal bleeding. Furthermore, whole exome sequencing was performed in the patient and additional family members to identify potential causative genetic variants that may cause intestinal iron loss. Under different inheritance models, several rare mutations were identified, two of which (in CISD1 and KRI1) are likely to be functionally relevant. Intestinal iron loss in the current form has not yet been described and is, with high probability, the cause of the severe iron deficiency anemia in this patient.

Application of Bayesian Decision Tree in Hematology Research: Differential Diagnosis of ß-Thalassemia Trait from Iron Deficiency Anemia.

OBJECTIVE: Several discriminating techniques have been proposed to discriminate between ß-thalassemia trait (ßTT) and iron deficiency anemia (IDA). These discrimination techniques are essential clinically, but they are challenging and typically difficult. This study is the first application of the Bayesian tree-based method for differential diagnosis of ßTT from IDA. METHOD: This cross-sectional study included 907 patients with ages over 18 years old and a mean (±SD) age of 25 ± 16.1 with either ßTT or IDA. Hematological parameters were measured using a Sysmex KX-21 automated hematology analyzer. Bayesian Logit Treed (BLTREED) and Classification and Regression Trees (CART) were implemented to discriminate ßTT from IDA based on the hematological parameters. RESULTS: This study proposes an automatic detection model of beta-thalassemia carriers based on a Bayesian tree-based method. The BLTREED model and CART showed that mean corpuscular volume (MCV) was the main predictor in diagnostic discrimination. According to the test dataset, CART indicated higher sensitivity and negative predictive value than BLTREED for differential diagnosis of ßTT from IDA. However, the CART algorithm had a high false-positive rate. Overall, the BLTREED model showed better performance concerning the area under the curve (AUC). CONCLUSIONS: The BLTREED model showed excellent diagnostic accuracy for differentiating ßTT from IDA. In addition, understanding tree-based methods are easy and do not need statistical experience. Thus, it can help physicians in making the right clinical decision. So, the proposed model could support medical decisions in the differential diagnosis of ßTT from IDA to avoid much more expensive, time-consuming laboratory tests, especially in countries with limited recourses or poor health services.

Iron Deficiency Anemia in Inflammatory Bowel Diseases-A Narrative Review.

Inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis, is characterized by chronic inflammation of the gastrointestinal tract. IBD has been associated with numerous symptoms and complications, with the most common being iron deficiency anemia (IDA). Iron deficiency in IBD is caused by inadequate intake, malabsorption (including duodenal involvement and surgical removal), and chronic blood loss by mucosal ulcerations. Therefore, an appropriate diet should be enforced. Iron deficiency and iron supplementation have been associated with alterations to gut microbiota. IBD-associated anemia, in particular iron deficiency anemia, is associated with a significant decrease in quality of life and with clinical symptoms such as chronic fatigue, headaches and dizziness, reduced exercise tolerance, pale skin, nails, conjunctiva, and fainting. However, despite these numerous adverse symptoms, IDA remains undertreated. The European Crohn's and Colitis Organisation (ECCO) guidelines state that patients should be monitored for anemia. Adequate treatment, whether oral or intravenous, should be implemented while taking into consideration C-reactive protein values (CRP), hemoglobin levels, and therapeutic response. It should be stressed that every case of anemia in IBD patients should be treated. Intravenous iron formulations, which are more superior compared to the oral form, should be used. There is a need to increase awareness and implementation of international guidelines on iron supplementation in patients with IBD.

Incidence and predictors of iron deficiency anaemia in parturients undergoing elective caesarean section at a tertiary hospital in New Zealand: a retrospective, observational cohort study.

BACKGROUND: Worldwide, iron deficiency anaemia in pregnancy is a significant problem which can be especially problematic when delivery is by caesarean section, a procedure associated with significant blood loss. Optimising iron stores pre-delivery remains an overarching goal. We aim to measure the incidence of iron deficiency anaemia in patients undergoing elective caesarean section at our institution and determine any associated predictors, as well as adverse outcomes. METHODS: A retrospective, observational cohort study of patients presenting for elective caesarean section over a two-year period. Patient data was collected from hospital electronic records. Iron deficiency anaemia was defined a haemoglobin < 110 g/L and a ferritin < 30 µg/L in the three-month period prior to delivery. The primary aim was to establish the incidence of iron deficiency anaemia at the time of delivery and any associated predictors. Secondary outcomes included any association between the primary outcome and complications defined by the hospital discharge complication coding system, as well as an evaluation of the number of blood tests carried out antenatally per trimester. RESULTS: One thousand and ninety-three women underwent caesarean section over the study period and 16.2% had iron deficiency anaemia. Patients with iron deficiency anaemia were more likely to be of Maori and Pacific Island ethnicity, have a greater booking body mass index, be younger and have a greater parity. Pre-operative anaemia was associated with a greater likelihood of post-operative blood transfusion. CONCLUSIONS: There remains potential for optimisation of iron deficiency anaemia in our local population undergoing elective caesarean section.

Comparative Evaluation of Sucrosomial Iron and Iron Oxide Nanoparticles as Oral Supplements in Iron Deficiency Anemia in Piglets.

Iron deficiency is the most common mammalian nutritional disorder. However, among mammalian species iron deficiency anemia (IDA), occurs regularly only in pigs. To cure IDA, piglets are routinely injected with high amounts of iron dextran (FeDex), which can lead to perturbations in iron homeostasis. Here, we evaluate the therapeutic efficacy of non-invasive supplementation with Sucrosomial iron (SI), a highly bioavailable iron supplement preventing IDA in humans and mice and various iron oxide nanoparticles (IONPs). Analysis of red blood cell indices and plasma iron parameters shows that not all iron preparations used in the study efficiently counteracted IDA comparable to FeDex-based supplementation. We found no signs of iron toxicity of any tested iron compounds, as evaluated based on the measurement of several toxicological markers that could indicate the occurrence of oxidative stress or inflammation. Neither SI nor IONPs increased hepcidin expression with alterations in ferroportin (FPN) protein level. Finally, the analysis of the piglet gut microbiota indicates the individual pattern of bacterial diversity across taxonomic levels, independent of the type of supplementation. In light of our results, SI but not IONPs used in the experiment emerges as a promising nutritional iron supplement, with a high potential to correct IDA in piglets.

Comparison of Iron Dosing Strategies in Patients Undergoing Long-Term Hemodialysis: A Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: Whether iron supplementation in patients on hemodialysis could be delivered by less frequent but higher single doses compared with the currently more common higher-frequency schedules of lower single iron doses is unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We carried out an open-label, randomized, controlled noninferiority trial over 40 weeks in patients on prevalent hemodialysis (n=142). We administered in total 2 g iron as 100 mg iron sucrose biweekly in a continuous (20 × 100 mg) fashion or 500 mg ferric carboxymaltose every 10 weeks in a periodic (4 × 500 mg) fashion. The primary end point was the change in hemoglobin at week 40 from baseline with a noninferiority margin of -0.8 g/dl. Secondary end points were changes in ferritin, transferrin, transferrin saturation, and erythropoiesis-stimulating agent use. RESULTS: In total, 108 patients completed the study. At 40 weeks, hemoglobin changed by -0.27 g/dl (95% confidence interval, -0.64 to 0.09) in the iron sucrose arm and by -0.74 g/dl (95% confidence interval, -1.1 to -0.39) in the ferric carboxymaltose arm compared with baseline. Noninferiority was not established in the per-protocol population as hemoglobin changes compared with baseline differed by -0.47 g/dl (95% confidence interval, -0.95 to 0.01) in the ferric carboxymaltose arm compared with the iron sucrose arm. Proportional changes from baseline to week 40 differed by -31% (98.3% confidence interval, -52 to -0.1) for ferritin, by 1% (98.3% confidence interval, -7 to 10) for transferrin, and by -27% (98.3% confidence interval, -39 to -13) for transferrin saturation in the ferric carboxymaltose arm compared with the iron sucrose arm. Erythropoiesis-stimulating agent dosing did not differ between groups. The overall number of adverse events was similar; however, more infections were observed in the iron sucrose arm. CONCLUSIONS: An equal cumulative dose of ferric carboxymaltose administered less frequently did not meet noninferiority for maintaining hemoglobin levels compared with iron sucrose administered more frequently. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Comparison Study of Two Iron Compounds for Treatment of Anemia in Hemodialysis Patients (COPEFER), NCT02198495.

Iron Deficiency in Vegetarian and Omnivorous Individuals: Analysis of 1340 Individuals.

The objective of this study was to evaluate the serum levels of ferritin and the prevalence of iron deficiency in vegan and omnivorous individuals by taking into account the presence of elements that cause an elevation of ferritin levels, such as increased homeostatic model assessment of insulin resistance (HOMA-IR), body mass index (BMI), and high-sensitivity C-reactive protein (hs-CRP) values. The parameters were evaluated in 1340 individuals, i.e., 422 men and 225 women who do not menstruate and 693 women who do menstruate, based on omnivorous or vegetarian eating habits. The progressive increase in BMI, HOMA-IR, and inflammation caused an elevation in ferritin concentration, regardless of the eating habits in the groups studied. In the overall sample, omnivores had a higher prevalence of obesity, higher ferritin levels, and a lower prevalence of iron deficiency (ferritin < 30 ng/mL). However, after the exclusion of individuals with inflammation (with overweight/obesity and elevated hs-CRP levels), the actual iron deficiency was assessed and was not higher among vegetarians, except in women with regular menstrual cycles. Our data show that nutritional status and inflammation levels affect ferritin levels and may interfere with the correct diagnosis of iron deficiency in both vegetarian and omnivorous individuals. Compared to vegetarians, women who do not menstruate and men had the same prevalence of iron deficiency when following an omnivorous diet.

Baseline iron status and presence of anaemia determine the course of systemic Salmonella infection following oral iron supplementation in mice.

BACKGROUND: Iron deficiency anaemia (IDA) is a major health concern. However, preventive iron supplementation in regions with high burden of infectious diseases resulted in an increase of infection related morbidity and mortality. METHODS: We fed male C57BL/6N mice with either an iron deficient or an iron adequate diet. Next, they received oral iron supplementation or placebo followed by intraperitoneal infection with Salmonella Typhimurium (S.Tm). FINDINGS: We found that mice with IDA had a poorer clinical outcome than mice on an iron adequate diet. Interestingly, iron supplementation of IDA mice resulted in higher bacterial burden in organs and shortened survival. Increased transferrin saturation and non-transferrin bound iron in the circulation together with low expression of ferroportin facilitated the access of the pathogen to iron and promoted bacterial growth. Anaemia, independent of iron supplementation, was correlated with reduced neutrophil counts and cytotoxic T cells. With iron supplementation, anaemia additionally correlated with increased splenic levels of the cytokine IL-10, which is suggestive for a weakened immune control to S.Tm infection. INTERPRETATION: Supplementing iron to anaemic mice worsens the clinical course of bacterial infection. This can be traced back to increased iron delivery to bacteria along with an impaired anti-microbial immune response. Our findings may have important implications for iron supplementation strategies in areas with high endemic burden of infections, putting those individuals, who potentially profit most from iron supplementation for anaemia, at the highest risk for infections. FUNDING: Financial support by the Christian Doppler Laboratory for Iron Metabolism and Anemia Research.

TMPRSS6 rs855791 Polymorphism Status in Children with Celiac Disease and Anemia.

Celiac disease (CD) is an autoimmune chronic inflammatory disease occurring in genetically predisposed individuals in response to the intake of gluten. Clinical presentation can be heterogeneous. Iron-deficient anemia (IDA) is one of the most common extra-intestinal manifestations of CD. Although IDA usually reverts with a gluten-free diet (GFD), some patients show persistent IDA, the mechanisms of which are poorly understood. Recent studies suggest an association between the rs855791 polymorphism in the TMPRSS6 gene and persistent IDA in adults with CD. The current study aimed to assess the potential link between rs855791 and persistent IDA in pediatric patients with CD. The study included 106 children diagnosed with CD between 2015 and 2019. Clinical and blood parameters (including blood count, serum iron) were collected at diagnosis and after ≥12 months of GFD, and the rs855791 genotype was assessed for each patient. IDA was present at diagnosis in 25 patients (23.6%); only three (3%) had persistent IDA after GFD. The prevalence of rs855791 genotypes was 9% (n = 10) for TT, 53% (n = 56) for CT, and 38% (n = 40) for CC. There was a tendency toward a higher proportion of the T allele in patients with IDA and lower hemoglobin in the TT genotype but without statistical significance. An association between rs855791 and persistent IDA was not observed. These findings suggest that persistent IDA is uncommon in pediatric patients with CD. The prevalence of rs855791 in children with CD is reported for the first time.

Clinical utility of Abbott Alinity hq extended red blood cell parameters in differentiating ß-thalassemia trait and iron deficiency anemia.

INTRODUCTION: The objective of the study was to evaluate the performance of the Abbott Alinity hq advanced multi angle polarized scatter separation (MAPSSTM )-based optical RBC technology, for the differentiation between iron deficiency anemia (IDA) and ß-thalassemia carrier status. METHODS: Four hundred and sixty-four samples were analyzed. 228 were healthy controls, 30 were ß-thalassemia carriers, and 40 were IDA. Receiver operating characteristics analysis evaluated the performance of red cell parameters and mathematical formulas. RESULTS: RBC concentration was the most efficient discriminant (area under the curve; AUC of 0.963, Youden Index of 0.88) followed by red blood cell distribution width in size distribution (AUC of 0.960 and YI of 0.86), and red blood cell distribution width coefficient of variation (AUC of 0.924, and YI of 0.74). The absolute reticulocyte concentration showed good diagnostic efficiency, with AUC of 0.808. Hemoglobin distribution width, the %CV of directly measured cellular hemoglobin concentration, and CHCr, the average hemoglobin concentration of reticulocytes have emerged as novel discriminating parameters, with AUC of 0.749 and 0.785, respectively. The England and Fraser index was the best discriminating mathematical formula based on Youden Index of 0.91. The Ricerca, red blood cell distribution width index, Green and King, and Mentzner Index formulas also showed strong discriminative power. The Shine and Lal index, together with the recent mathematical formula M/H, (ratio of percent microcytic and hypochromic red blood cells) demonstrated moderate performance with AUC of 0.796 and 0.740, respectively. CONCLUSION: Extended red cell analysis delivered by the advanced optical technology on the Alinity hq hematology analyzer has efficient diagnostic utility in the initial discrimination of the two most common microcytic anemias: IDA and ß-thalassemia trait.