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This cross-sectional study, conducted on a population-based representative sample, evaluates the usefulness of reticulocyte haemoglobin content (CHr), serum transferrin receptor (sTfR) and sTfR/log ferritin (sTfR-F index) to recognise iron deficiency (ID) without anaemia, provides specific cut-off points for age and gender, and proposes a new definition of ID. A total of 1239 healthy children and adolescents aged 1–16 years were included. Complete blood count, iron biomarkers, erythropoietin, C-reactive protein, CHr, sTfR, and sTfR-F index were determined. ROC curves were obtained and sensitivity, specificity, predictive values, likelihood ratios, and accuracy for each specific cut-off points were calculated. Seventy-three had ID without anaemia. Area under the curve for sTfR-F index, sTfR and CHr were 0.97 (CI95% 0.95–0.99), 0.87 (CI95% 0.82–0.92) and 0.68 (CI95% 0.61–0.74), respectively. The following cut-off points defined ID: sTfR-F Index > 1.5 (1–5 years and 12–16 years boys) and > 1.4 (6–11 years and 12–16 years girls); sTfR (mg/L) > 1.9 (1–5 years), > 1.8 (6–11 years), > 1.75 (12–16 years girls) and > 1.95 (12–16 years boys); and CHr (pg) < 27 (1–5 years) and < 28.5 (6–16 years).Conclusions: CHr, sTfR and the sTfR-F index are useful parameters to discriminate ID without anaemia in children and adolescents, and specific cut-off values have been established. The combination of these new markers offers an alternative definition of ID with suitable discriminatory power.What is Known:• In adults, reticulocyte haemoglobin content (CHr), serum transferrin receptor (sTfR) and sTfR/log ferritin index (sTfR-F index) have been evaluated and recognised as reliable indicators of iron deficiency (ID).• Clinical manifestations of ID may be present in stages prior to anaemia, and the diagnosis of ID without anaemia continues to pose problems.What is New:• CHr, sTfR and the sTfR-F index are useful parameters in diagnosis of ID in childhood and adolescence when anaemia is not present.• We propose a new strategy for the diagnosis of ID in childhood and adolescence, based on the combination of these measures, which offer greater discriminatory power than the classical parameters.

Iron deficiency (ID) is the most common nutritional deficiency affecting children worldwide. Most traditional laboratory parameters to assess ID can be altered by infections or other inflammatory states, including obesity. The aims of this study were to determine the prevalence of ID in healthy children and to analyse associated factors, avoiding potential confounding factors through the use of serum transferrin receptor (sTfR), reticulocyte haemoglobin content and sTfR/log ferritin index. A cross-sectional population-based study was conducted on 951 children aged 1 to 11 years in Almería (Spain). ID was detected in 7.7% of children and iron deficiency anaemia in 0.9%. Multivariate analysis identified the following as independent risk factors: age under 5 years (OR: 2.2, 95% CI: 1.35–3.6); excessive consumption of cow’s milk and dairy products (OR: 1.87, 95% CI: 1.13–3.1); and insufficient consumption of vegetables (OR: 2.7, 95% CI: 1.2–6.1).Conclusions: Using a combination of iron status parameters with greater discriminatory power than classical measures, this study detected a considerable iron deficiency prevalence in Spanish children. Younger children and specific dietary habits exhibit a particular risk for ID, so special attention should be paid to this population. What is Known:• Iron deficiency remains the most prevalent nutritional deficit worldwide, and children aged under 3 years are the most vulnerable to this condition.• Accurate assessment of iron status, based on a combination of biochemical indicators, can often be complicated.What is New:• Iron deficiency continues to present a health problem in Spanish children aged 1 to 11 years, considering the serum transferrin receptor and reticulocyte haemoglobin content for diagnosis.• Excessive consumption of dairy products and low consumption of vegetables are independent risk factors for iron deficiency.

Maternal infections, nutrient deficiencies, and inflammation (MINDI) co-exist in lactating indigenous women in Panama, but their impact on maternal iron status and infant growth is unknown. For this secondary analysis of cross-sectional data of lactating mothers from our MINDI cohort, we investigated associations of MINDI variables with maternal anemia, elevated serum transferrin receptor (sTfR), low serum iron, hepcidin, ferritin, and infant weight-for-age (WAZ), length-for-age (LAZ), and head-circumference-for-age (HCAZ) Z-scores in 99 mother-infant dyads. A bootstrapping resampling procedure preselected covariates for inclusion in multivariable regressions models from chronic maternal infections and nutritional status [folate, vitamins A, D, retinol-binding protein (RBP), insulin-growth factor-1 (IGF-1)] and inflammation [C-reactive protein (CRP), cytokines, platelet indices] indicators. Anemia was prevalent (53.5%) but underestimated due to widespread low plasma volume (<2.2 L, 79.9%) and was associated with indicators of malnutrition [lower IGF-1, body mass index (BMI), vitamin D, and intake of green/leafy vegetables], but not inflammation. Higher CRP was associated with lower serum iron, and higher hepcidin and ferritin, whereas maternal platelets were associated with lower HCAZ (β = −0.22), WAZ (β = −0.17), and LAZ (β = −0.17). Higher LAZ was also associated with maternal serum vitamin D (β = 0.23), whereas maternal iron supplementation lowered LAZ (β = −0.22). Assessment of iron status in this MINDI cohort is complex and supplementation strategies must consider consequences for both the mother and the infant.

Background: Overweight is increasing in transition countries, while iron deficiency remains common. In industrialized countries, greater adiposity increases risk of iron deficiency. Higher hepcidin levels in obesity may reduce dietary iron absorption. Therefore, we investigated the association between body mass index (BMI) and iron absorption, iron status and the response to iron fortification in populations from three transition countries (Thailand, Morocco and India). Methods: In Thai women (n=92), we examined the relationship between BMI and iron absorption from a reference meal containing 4 mg of isotopically labeled fortification iron. We analyzed data from baseline (n=1688) and intervention (n=727) studies in children in Morocco and India to look for associations between BMI Z-scores and baseline hemoglobin, serum ferritin and transferrin receptor, whole blood zinc protoporphyrin and body iron stores, and changes in these measures after provision of iron. Results: In the Thai women, 20% were iron deficient and 22% were overweight. Independent of iron status, a higher BMI Z-score was associated with decreased iron absorption (P=0.030). In the Indian and Moroccan children, 42% were iron deficient and 6.3% were overweight. A higher BMI Z-score predicted poorer iron status at baseline (P<0.001) and less improvement in iron status during the interventions (P<0.001). Conclusions: Adiposity in young women predicts lower iron absorption, and pediatric adiposity predicts iron deficiency and a reduced response to iron fortification. These data suggest the current surge in overweight in transition countries may impair efforts to control iron deficiency in these target groups. Interactions of the 'double burden' of malnutrition during the nutrition transition may have adverse consequences.

Iron deficiency anaemia continues to be the world’s most important cause of years lived with disability in children and adolescents. Assessment of iron deficiency traditionally depended on laboratory parameters that may be modified by inflammation states, including obesity, which is nowadays a current condition in adolescent population of high-income countries. The present study ascertains the prevalence of iron deficiency and its related factors in adolescents, using the serum transferrin receptor and the reticulocyte haemoglobin content, in order to avoid this confusing effect of classical parameters. A cross-sectional study was conducted on a population-based representative sample for teenagers in Almería (Spain), of 405 subjects aged 12 to 16 years. Iron deficiency was present in 13.3% of adolescents, but iron deficiency anaemia only in 1.2%. Multivariate logistic regression analyses showed that being part of an immigrant family, a low iron bioavailability diet, meat consumption below four times a week and fish consumption below twice a week, were independent risk factors for iron deficiency.Conclusion: This study provides an estimate iron deficiency prevalence of 13.3% in Spanish healthy adolescents, avoiding potential confounding factors through the use of new iron status parameters, based on a wide representative sample of adolescents from the city of Almería.What is Known:• For children and adolescents, iron deficiency anaemia continues to be the world’s most important cause of years lived with disability.• Assessment of iron deficiency has traditionally depended on laboratory parameters that may be modified by inflammatory states, including obesity.What is New:• Iron deficiency prevalence and their related factors were analysed in Spanish adolescents, avoiding potential confounding factors through the use of sTfR and CHr.• Being part of an immigrant family and consuming a low iron bioavailability diet are independent risk factors for iron deficiency.

Hemoglobin (Hb), mean cell volume (MCV), and erythrocyte protoporphyrin (EP) are commonly used to screen for iron deficiency (ID), but systematic evaluation of the sensitivity and specificity of these tests is limited. The objective of this study is to determine the sensitivity and specificity of Hb, MCV, and EP measurements in screening for ID in preschool children, non-pregnant women 15–49 years of age, and pregnant women. Data from the National Health and Nutrition Examination Surveys (NHANES) (NHANES 2003–2006: n = 861, children three to five years of age; n = 3112, non-pregnant women 15 to 49 years of age. NHANES 1999–2006: n = 1150, pregnant women) were examined for this purpose. Children or women with blood lead ≥10 µg/dL or C-reactive protein (CRP) >5.0 mg/L were excluded. ID was defined as total body iron stores <0 mg/kg body weight, calculated from the ratio of soluble transferrin receptor (sTfR) to serum ferritin (SF). The receiver operating characteristic (ROC) curve was used to characterize the sensitivity and specificity of Hb, MCV, and EP measurements in screening for ID. In detecting ID in children three to five years of age, EP (Area under the Curve (AUC) 0.80) was superior to Hb (AUC 0.62) (p < 0.01) but not statistically different from MCV (AUC 0.73). In women, EP and Hb were comparable (non-pregnant AUC 0.86 and 0.84, respectively; pregnant 0.77 and 0.74, respectively), and both were better than MCV (non-pregnant AUC 0.80; pregnant 0.70) (p < 0.01). We concluded that the sensitivity and specificity of EP in screening for ID were consistently superior to or at least as effective as those of Hb and MCV in each population examined. For children three to five years of age, EP screening for ID was significantly better than Hb and similar to MCV. For both non-pregnant and pregnant women, the performance of EP and Hb were comparable; both were significantly superior to MCV.

Background Non-transfusion-dependent thalassemia (NTDT) is a significant global health issue that affects nearly 90 million individuals worldwide. NTDT is a form of chronic anemia that can lead to bone pain, deformities, and hepatosplenomegaly. Soluble transferrin receptor-1 (sTfR) is proposed as a biomarker to assess NTDT severity and predict blood transfusion requirements, yet its diagnostic value remains unclear. This study aimed to evaluate the role of sTfR as a diagnostic and predictive marker for NTDT severity and blood transfusion requirements. This case–control study included 34 NTDT and 33 healthy controls matched for age and sex. Diagnosis was made based on clinical examination, hemoglobin (Hb) electrophoresis, high-performance liquid chromatography (HPLC), and genetic testing. sTfR and serum transferrin were measured; also, sTfR/ferritin ratio was reported. Results NTDT patients showed a significantly higher levels of sTfR (1201.56 ± 892.43 nmol/L) and serum ferritin (171.04 ± 17.92 ng/mL) compared to the healthy control group ( p  < 0.001). The sTfR/ferritin ratio was significantly lower in NTDT patients (0.26 ± 0.27) compared to the healthy control group (0.46 ± 0.14) ( p  < 0.001). Additionally, a strong positive correlation was found between sTfR levels and blood transfusion frequency, with a sensitivity and specificity of 100% at a cutoff of ≥ 196.2 nmol/L ( AUC  = 1.00). Serum ferritin also showed diagnostic value but with lower sensitivity and specificity (62.96% and 57.14%, respectively). Conclusion This study suggests that sTfR may assist in evaluating NTDT severity and transfusion needs, potentially supporting clinical decision-making if validated in future studies.

The aim of this study was to analyze the relationship between the serum levels of soluble transferrin receptor (sTfR) and interleukin 4 (IL-4), and the disease activity and organ manifestations in SLE patients. We studied 200 SLE patients and 50 controls. We analyzed disease activity, organ involvement, serum sTfR, IL-4 and interleukin-6 (IL-6) levels, and antinuclear and antiphospholipid antibody profiles. The median serum levels of sTfR (p > 0.000001) and IL-4 (p < 0.00001) were higher in the study group than in the controls. SLE patients, compared to the controls, had significantly lower HGB levels (p < 0.0001), a lower iron concentration (p = 0.008), a lower value of total iron-binding capacity (TIBC) (p = 0.03), and lower counts of RBC (p = 0.004), HCT (p = 0.0004), PLT (p = 0.04), neutrophil (p = 0.04), and lymphocyte (p < 0.0001). Serum sTfR levels were negatively correlated with lymphocyte (p = 0.0005), HGB (p = 0.0001) and HCT (p = 0.008), and positively correlated with IL-4 (p = 0.01). Elevated serum sTfR > 2.14 mg/dL was associated with an increased risk of myocardial infarction (OR: 10.6 95 CI 2.71–464.78; p = 0.001), ischemic heart disease (OR: 3.25 95 CI 1.02–10.40; p = 0.04), lung manifestations (OR: 4.48 95 CI 1.44–13.94; p = 0.01), and hematological manifestations (OR: 2.07 95 CI 1.13–3.79; p = 0.01), and with a reduced risk of neuropsychiatric manifestations (OR: 0.42 95 CI 0.22–0.80; p = 0.008). Serum IL-4 was negatively correlated with CRP (p = 0.003), and elevated serum IL-4 levels > 0.17 mg/L were associated with a reduced risk of mucocutaneous manifestations (OR: 0.48 95 CI 0.26–0.90; p = 0.02). In SLE patients, elevated serum levels of sTfR were associated with an increased risk of cardiovascular, pulmonary, and hematological manifestations, and with a decreased risk of neuropsychiatric manifestations. In contrast, elevated serum IL-4 levels were associated with a decreased risk of mucocutaneous manifestations.

Anaemia is still a public health problem in Indonesia. The iron supplement program, known as Tablet Tambah Darah (Blood Add Tablet) has not yet produced optimal results. This study aimed to identify the cause of anaemia and the factors that influence it. Biochemical indicator data are haemoglobin (Hb), C-reactive protein (CRP), ferritin and serum transferrin receptor (sTfR) from 9,463 women of reproduction age. Data from the Basic Health Research (Riskesdas) project of 2013 were used for the study. ANOVA as well as global and local regression approaches (classical regression and geo-weighted regression) were used to compare the mean Hb and CRP values between provinces and to determine the factors that influence Hb concentrations. The results showed that the distribution of anaemia in Indonesia is uneven and not always caused by iron deficiency. The lowest Hb mean coupled with the highest iron deficiency was found in Papua, where there are high rates of parasitic infections. In contrast, the highest mean Hb coupled with low iron deficiency, and also low infection rates, was found in North Sulawesi. The Hb concentrations were significantly associated by ferritin, CRP and sTfR and there were varying magnitudes between provinces. Although anaemia is mainly influenced by the iron concentration, CRP, ferritin and sTfR can also affect it through their association with inflammatory reactions. Identification of all causes of anaemia in each province needs to be done in the future, while blanket iron supplementation should be reviewed.

Background Anaemia is one of the world’s most prevalent child health problems. Its control in Africa and other developing nations has been hindered by uncertainty regarding its cause. Anaemia control has been particularly problematic in regions where the non-iron deficiency causes of anaemia, are projected to be substantial. The implementation of effective interventions to reduce the anaemia prevalence, requires improved documentation on iron status and other causes of anaemia for target populations. Methods This cross-sectional study enrolled n = 184 children, aged 6–8 years from Kwazulu-Natal, South Africa. Tests of haemoglobin, serum ferritin, soluble transferrin receptor and C-reactive protein were performed. These conventional measures of iron status were used to calculate body iron and to categorize the children into different groups of anaemia profiles. Results Anaemia prevalence was high, 43/184 (23.4%). Iron deficiency anaemia contributed 7/43 (16.3%) to the anaemia prevalence compared to non-iron deficiency anaemia 34/43 (79.1%) and mixed anaemia 2/43 (4.7%). In total 47/184 (25.5%) of the sampled children had either iron deficiency or anaemia. Information about the presence of inflammation was used to adjust serum ferritin concentrations, resulting in improved diagnosis of iron deficiency. Conclusion Appropriate investigations for iron status and inflammation/infection screening, need to be integral in the evaluation of anaemia and its causes before anaemia control interventions are implemented. Interventions that target the multifactorial nature of anaemia in school-aged children need to be strengthened. Additionally, regular screening of anaemia in school-aged children from disadvantaged communities is recommended.