Lower Ferritin Concentrations Research Articles

Meconium Transferrin and Ferritin as Markers of Homeostasis in the Developing Fetus.

The molecular mechanisms regulating homeostasis in the developing fetus have not been satisfactorily elucidated. Meconium contains substances accumulated in the fetal intestines. Measurements of transferrin and ferritin concentrations in meconium and assessment of transferrin-ferritin relationships could enhance knowledge about specific processes of the intrauterine period involving the two proteins and their effects on the development and growth of the fetus. Transferrin and ferritin concentrations were measured by ELISA in the homogenates of first meconium portions from 125 neonates. Higher birth weight was associated with lower ferritin concentrations in meconium (r = -0.22, p = 0.015). In neonates with a birth weight of more than 3750 g, there was a positive correlation between transferrin and ferritin concentrations (r = 0.51, p = 0.003). With meconium transferrin concentrations above 43.52 µg/g, a negative correlation between transferrin and ferritin was established (r = -0.37, p = 0.036), while with transferrin concentrations below 43.52 µg/g, the correlations between the birth weight and the meconium transferrin and ferritin concentrations were negative (r = -0.61, p < 0.001 and r = -0.43, p = 0.017, respectively). Measurements of transferrin and ferritin in meconium specimens create a new use for these common biomarkers to improve our understanding of the effects of homeostasis in utero on the fetal development and growth. Establishing reference ranges of meconium transferrin and ferritin concentrations and their association with the clinical parameters during pregnancy could aid in the assessment of the impact of intrauterine life on the health status of the neonate and its adaptation to extrauterine life.

Reduced levels of hepcidin associated with lower ferritin concentration and increased number of previous donations in periodic blood donors: a pilot study.

Hepcidin is one of the major negative regulators of iron balance. Periodic blood donors are highly susceptible to have iron deficiency. Our goal was to evaluate the possible association between serum hepcidin levels and iron homeostasis parameters in periodic blood donors. We enrolled a total of n=39 periodic healthy blood donors (n=24 M and n=15 F). A solid phase enzyme-linked immunosorbent assay (ELISA) was used to measure endogenous hepcidin-25 levels in serum biospecimens collected from each study participant. Statistical analysis was performed to evaluate possible associations between hepcidin levels and ferritin, transferrin, total iron binding capacity (TIBC), unsaturated iron binding capacity (UIBC), transferrin saturation (TSAT), and number of previous donations. Reduced serum hepcidin levels significantly correlated with reduced serum ferritin concentration (r = 0.56, IC95%: 0.51-0.60, p < 0.01). A multiple linear regression analysis showed that hepcidin levels were independently and negatively correlated with ferritin (p < 0.01). In addition, the number of previous blood donations was significantly associated with reduced hepcidin levels, independently of the other covariates (p < 0.01). Reduced serum hepcidin levels were significantly associated with reduced levels of ferritin and with increased number of previous donations suggesting its possible clinical role as non-invasive "point-of-care" in predicting iron deficiency among periodic blood donors.

Automated prediction of low ferritin concentrations using a machine learning algorithm.

Computational algorithms for the interpretation of laboratory test results can support physicians and specialists in laboratory medicine. The aim of this study was to develop, implement and evaluate a machine learning algorithm that automatically assesses the risk of low body iron storage, reflected by low ferritin plasma levels, in anemic primary care patients using a minimal set of basic laboratory tests, namely complete blood count and C-reactive protein (CRP). Laboratory measurements of anemic primary care patients were used to develop and validate a machine learning algorithm. The performance of the algorithm was compared to twelve specialists in laboratory medicine from three large teaching hospitals, who predicted if patients with anemia have low ferritin levels based on laboratory test reports (complete blood count and CRP). In a second round of assessments the algorithm outcome was provided to the specialists in laboratory medicine as a decision support tool. Two separate algorithms to predict low ferritin concentrations were developed based on two different chemistry analyzers, with an area under the curve of the ROC of 0.92 (Siemens) and 0.90 (Roche). The specialists in laboratory medicine were less accurate in predicting low ferritin concentrations compared to the algorithms, even when knowing the output of the algorithms as support tool. Implementation of the algorithm in the laboratory system resulted in one new iron deficiency diagnosis on average per day. Low ferritin levels in anemic patients can be accurately predicted using a machine learning algorithm based on routine laboratory test results. Moreover, implementation of the algorithm in the laboratory system reduces the number of otherwise unrecognized iron deficiencies.

Iron deficiency anemia among children aged 2-5 years in southern Ethiopia: a community-based cross-sectional study.

BackgroundIron-deficiency anemia (IDA) is a common type of nutritional anemia in low-income countries, including Ethiopia. However, there is limited data on iron deficiency anemia prevalence and associated factors in Ethiopia, particularly for children aged 2 to 5 years.ObjectivesTo establish the prevalence of iron deficiency anemia and associated risk factors, focusing on iron-rich food consumption among children aged 2 to 5 years in southern Ethiopia.MethodsA community-based cross-sectional study was conducted in southern Ethiopia in 2017, involving 331 randomly selected children aged 2 to 5 years old. A structured questionnaire was used to collect information about the children and the households. Venous blood was collected from each child in a test tube to measure hemoglobin, ferritin, and C-reactive protein (CRP). Hemoglobin levels were determined using Hemocue®301 and adjusted for altitude. Anemia was defined as hemoglobin levels <11 g/dl. Ferritin was adjusted for inflammation based on CRP concentration and low ferritin concentration defined as adjusted ferritin concentration <12 µg/L. IDA was considered when a child had both hemoglobin level <11g/dl and low ferritin concentration. Bi-variable and multivariable logistic regression models were performed to identify factors associated with IDA and iron-rich food consumption.ResultsThe prevalence of iron deficiency anemia was 25%, and the total anemia prevalence was 32%. Only 15% of children consumed iron-rich foods in the preceding 24 h, and 30% of children consumed iron-rich foods at least once in the preceding week. IDA decreased as the height for age z-score increased (Adjusted Odds Ratio 0.7; 95% CI [0.5–0.9]). Mothers with increased educational level (AOR 1.1; 1.0–1.2) and households with increased dietary diversity (AOR 1.4; 1.2–1.6) consumed more iron-rich foods.ConclusionsIron deficiency anaemia was a moderate public health problem in southern Ethiopia, and the iron-rich food consumption was low. Interventions should focus on food supplementation and fortification, food diversification and nutritional education, and promoting women’s education.

Menstrual blood losses and body mass index are associated with serum ferritin concentrations among female varsity athletes.

Preventing and treating iron deficiency are important components in the nutritional care of female varsity athletes, as these interventions may improve aerobic endurance and athletic performance. We examined the factors associated with ferritin concentration in 30 female varsity athletes (18-30 years) at the University of British Columbia in Vancouver, Canada. Biochemical indicators of iron and inflammation status, dietary intake, supplementation practices, weight, height, and menstrual blood losses were assessed. Iron deficiency prevalence was 20% (n = 6/30; inflammation-adjusted ferritin <15 μg/L). Multiple linear regression was used to assess the associations of a number of independent explanatory variables with log-transformed serum ferritin (μg/L) as the continuous outcome variable. A 1-unit increase in body mass index (BMI; kg/m2) was associated with 22% (95% CI: 9%-37%) higher mean ferritin concentrations, and a 1-point increase in menstrual loss score was associated with 1% (95% CI: 1%-2%) lower ferritin concentrations. Hemoglobin and hepcidin concentrations, inflammation biomarkers, consumption of iron supplements in any form or dose for ≥3 days/week, and age were not significantly associated with ferritin concentrations in the final adjusted model. Novelty Estimated monthly menstrual losses and BMI were associated with serum ferritin concentrations in female athletes in our study. These are easy-to-measure, noninvasive measurements that should be considered in the assessment of risk of iron deficiency in female athletes.

Dynamic iron status after acute heart failure

Iron deficiency (ID) is common in heart failure (HF), and is associated with unfavourable clinical outcomes. Although it is recommended to screen for ID in HF, there is no clear consensus on the optimal timing of its assessment. To analyse changes in iron status during a short-term follow-up in patients admitted for acute HF. Iron status (serum ferritin concentration and transferrin saturation) was determined in 110 consecutive patients (median age: 81 years) admitted to a referral centre for acute HF, at three timepoints (admission, discharge and 1 month after discharge). ID was defined according to the guidelines. The prevalence rates of ID at admission, discharge and 1 month were, respectively, 75% (95% confidence interval [CI] 67-83%), 61% (95% CI: 52-70%), and 70% (95% CI: 61-79%) (P=0.008). Changes in prevalence were significant between admission and discharge (P=0.0018). Despite a similar ID prevalence at admission and 1 month (P=0.34), iron status changed in 25% of patients. Between admission and discharge, variation in C-reactive protein correlated significantly with that of ferritin (ρ=0.30; P=0.001). Advanced age, anaemia, low ferritin concentration and low creatinine clearance were associated with the persistence of ID from admission to 1 month. Iron status is dynamic in patients admitted for acute HF. Although ID was as frequent at admission as at 1 month after discharge, iron status varied in 25% of patients.

Functional iron deficiency markers are absent during pregnancy despite evidence of low iron stores.

Introduction Functional iron deficiency parameters predict iron-restricted erythropoiesis more precisely than ferritin. Ferritin and erythropoiesis can be affected by inflammation and hormonal alterations. We hypothesize that the association between low ferritin concentrations and iron-restricted erythropoiesis is not comparable between pregnant and non-pregnant women. Materials and methods Pregnant women ( n = 926) were included at week 12 of gestation. Ferritin concentrations, %hypochromic erythrocytes (%HYPO), %microcytic erythrocytes (%MICRO), reticulocyte haemoglobin content (MCHr), mean cell volume (MCV) and mean cell haemoglobin (MCH) were analysed. Data were compared with non-pregnant women ( n = 1302). Results Functional iron deficiency parameters (%HYPO, %MICRO, MCHr) were present in, respectively, 3.9%, 14.3% and 2.3% off all pregnant women. Univariate analysis of low ferritin (&lt;20 μg/L) showed significant differences between non-pregnant versus pregnant women; %HYPO (10.92% vs. 0.92%), increased %MICRO (4.33% vs. 1.00%) and decreased MCHr (24.9 pg vs. 29.5 pg), respectively. In the logistic regression analysis, MCHr, %MICRO and MCV were independently associated with low ferritin concentrations in pregnant women, while %HYPO and %MICRO were independently associated variables in non-pregnant women with low ferritin concentrations. Discussion Functional iron deficiency is significantly less frequent in pregnant women compared with iron-deficient non-pregnant women. During pregnancy, iron metabolism might be differentially regulated for optimal fetal growth and development despite low maternal iron stores.

Biochemical effect of low metabolic calories diets on experimentally induced obesity on rats

This study aimed to evaluate the effect of weight loss diets in experimental obesity. Forty –five male albino rats, 6-8 weeks old, were randomly assigned into four groups: Group 1 (Control normal group) : Comprised 10 rats, provided only with regular diet and plenty of fresh. Group 2 ( Control obese group with 75 calories diet) : Included 10 rats ,was received a high fat diet for 4 weeks period then each rat was fed daily with 75 calories diet for 8weeks .Group 3 (Obese group with 60 calories diet): Included 10 rats ,was received a high fat diet for 4 weeks period then each rat was fed daily with 80% calories of the Control obese diet for 8weeks (60 calories diet) .Group 4 (Obese group with 45 calories diet) : Included 10 rats ,was received a high fat diet for 4 weeks period then each rat was fed daily with 60% calories of the Control obese diet for 8weeks (45 calories diet).Blood samples were collected after 8 and 12weeks of supplementation for biochemical analysis. As compared to the control normal group, control obese group exhibited a significant decrease in serum high density lipoprotein-cholesterol (HDL-c), transferrin and total iron bending capacity(TIBC), along with increase in aspartate aminotransferase (AST) activity, total protein, albumin, urea, creatinine, total cholesterol ,plasma triacylglycerol, very low density lipoprotein-cholesterol (VLDL-c), low density lipoprotein-cholesterol (LDL-c),sodium ,calcium , iron concentration and Plasma ferritin concentration. Meanwhile , the obese group provided with 60 calories diet exhibited a significant decrease in AST activity, total protein, albumin , urea, creatinine, total cholesterol , triacylglycerol ,VLDL-c, LDL-c, sodium ,calcium , iron concentration and ferritin along with increase in HDL-c, transferrin and TIBC when compared with obese group. However, the obese group provided with 45 calories diet, exhibited a significant decrease in total protein concentration, albumin, T. cholesterol, triacylglycerol, VLDL-c, LDL-c, sodium, calcium, iron concentration and ferritin along with increase in AST activity, urea, creatinine, HDL, transferrin and TIBC, when compared with obese group. In conclusion, Low calorie diet reduces calorie intake without incurring malnutrition or a reduction in essential nutrients compared with very low-calorie diet.

Intermittent iron supplementation for reducing anaemia and its associated impairments in adolescent and adult menstruating women.

Intermittent iron supplementation for reducing anaemia and its associated impairments in adolescent and adult menstruating women.

SERUM FERRITIN CONCENTRATION IS NOT A RELIABLE BIOMARKER OF IRON OVERLOAD DISORDER PROGRESSION OR HEMOCHROMATOSIS IN THE SUMATRAN RHINOCEROS (DICERORHINUS SUMATRENSIS).

The aim of this study was to determine if ferritin is a reliable biomarker of iron overload disorder (IOD) progression and hemochromatosis in the Sumatran rhinoceros (Dicerorhinus sumatrensis) by developing a species-specific ferritin assay and testing historically banked samples collected from rhinos that did and did not die of hemochromatosis. Ferritin extracted from Sumatran rhino liver tissue was used to generate antibodies for the Enzyme Immunoassay. Historically banked Sumatran rhino serum samples (n = 298) obtained from six rhinos in US zoos (n = 290); five rhinos at the Sumatran Rhino Conservation Centre in Sungai Dusun, Malaysia (n = 5); and two rhinos in Sabah, Malaysia (n = 3) were analyzed for ferritin concentrations. Across all US zoo samples, serum ferritin concentrations ranged from 348 to 7,071 ng/ml, with individual means ranging from 1,267 (n = 25) to 2,604 ng/ml (n = 36). The ferritin profiles were dynamic, and all rhinos exhibited spikes in ferritin above baseline during the sampling period. The rhino with the highest mean ferritin concentration did not die of hemochromatosis and exhibited only mild hemosiderosis postmortem. A reproductive female exhibited decreases and increases in serum ferritin concurrent with pregnant and nonpregnant states, respectively. Mean (±SD) serum ferritin concentration for Sumatran rhinos in Malaysia was high (4,904 ± 4,828 ng/ml) compared to that for US zoo rhinos (1,835 ± 495 ng/ml). However, those in Sabah had lower ferritin concentrations (1,025 ± 52.7 ng/ml) compared to those in Sungai Dusun (6,456 ± 4,941 ng/ml). In conclusion, Sumatran rhino serum ferritin concentrations are dynamic, and increases often are not associated with illness or hemochromatosis. Neither a specific pattern nor the individual's overall mean ferritin concentration can be used to accurately assess IOD progression or diagnose hemochromatosis in this rhino species.

Iron monitoring of male and female rugby sevens players over an international season.

Given the likely influence that high training loads, contact-induced hemolysis and female-specific requirements have on the incidence of iron deficiency, characterizing the direction and magnitude of fluctuations in iron status over an international season is important for managing player health and physical performance in rugby sevens. Australian national male (N.=27) and female (N.=23) rugby sevens players undertook blood tests at pre-season, mid-season, and end-season. Hemoglobin (Hb), hematocrit (Hct), ferritin, transferrin and transferrin saturation were quantified. Female athletes also reported oral contraceptive use and a subset (N.=7) provided 7-day food diaries to quantify iron intake. Male players typically had a three-fold higher ferritin concentration than females. Pre-season ferritin concentrations in male (151±66 µg/L) and female (51±24 µg/L) players declined substantially (~20%) by mid-season but recovered by end-season. Over the season 23% of female players were classified as iron deficient (ferritin <30 µg/L) and prescribed supplementation. The greatest incidence of iron deficiency in female players occurred mid-season (30%). Oral contraception and dietary iron intake had an unclear influence on female players' ferritin concentration, while age was largely positively correlated (r=0.66±~0.33). Given the relatively low ferritin concentrations evident in female rugby sevens players, and the potential for a further decline midway through a season when physical load may be at its highest, 6-monthly hematological reviews are suggested in combination with dietary management. Annual screening may be beneficial for male players, with further monitoring only when clinically indicated.

Conflicting effects of BMI and waist circumference on iron status

The association between obesity and iron status has a long history and is still receiving attention. However comparative analysis of the association between general obesity (BMI) and visceral obesity (waist circumference) with iron status has not been extensively researched. The aim of the present study is thus to determine if body mass index and waist circumference have the same correlation with iron status. One thousand one hundred and thirty people (225 men and 905 women) aged 30 years and above participated in this study. Anthropometric parameters, haemoglobin, iron and total iron binding capacity concentrations were measured using standard methods. Percentage transferrin saturation was calculated and ferritin concentrations were measured using an enzyme linked immunosorbent assay. Obese or overweight women had significantly lower iron and transferrin saturation concentration when compared to non-obese women. In contrast, women with high waist circumference had comparable plasma iron and transferrin saturation to women with normal waist circumference. Partial correlation analysis and linear regression analysis showed that BMI is negatively and significantly associated with plasma iron, transferrin saturation, Hb and ferritin concentration, whilst waist circumference is positively but insignificantly associated with plasma iron, transferrin saturation, Hb and ferritin concentration. Binary regression analysis showed that obese or overweight people are more likely to have iron deficiency, whilst those with raised waist circumference are more likely to have iron overload. Multivariate analysis showed that body mass index is negatively and significantly associated with low iron status, while waist circumference is positively and insignificantly associated with iron status. This is supported by a comparison of plasma iron, transferrin saturation and ferritin concentrations in participants with high body mass index and normal waist circumference and participants with normal body mass index and high waist circumference to those participants having normal body mass index and normal waist circumference. The present study suggests that in women body mass index is associated with low plasma iron, transferrin saturation and ferritin concentrations, while waist circumference is associated with high plasma iron, transferrin saturation and ferritin concentrations.

Influence of blood donation time intervals on ferritin and hemoglobin concentration

ObjectiveIdentify possible significant hemoglobin level variations between blood donations, and observe the effect of periodic donations on iron store. MethodsSeventy-seven subjects were monitored in the course of 1 year to evaluate if repetitive blood donations had an effect on hemoglobin and ferritin concentrations. Furthermore, we determined if hemoglobin concentration variation, detected by the cyanmethemoglobin method, could be used as an early marker for decreased ferritin concentration, quantified by ELISA. ResultsNo association between hemoglobin and ferritin variations was observed, as evidenced from our results. Ferritin variations were greater than 50% between donations; in contrast, hemoglobin remained unchanged within intra-individual biological fluctuations. We observed decreased ferritin values during the first blood donation in 15% of the men and 14% of the women evaluated. During the second blood donation 22% of men and 23% of women had decreased ferritin levels. During the third blood donation 43% of men and 50% of women had decreased ferritin values. Only men donated blood four times during the course of the year with all men having decreased ferritin levels. Decrease in ferritin was conditioned both by the number of blood donations as well as the periodicity between them. Spans greater than 6 months between blood donations reduced the risk of iron store reduction. ConclusionWe determined hemoglobin is not a sensitive marker for monitoring repetitive blood donor follow-up, since hemoglobin did not vary significantly between donations despite having very low or nil ferritin concentration values.

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.

Ferrotoxic Disease: The Next Great Public Health Challenge

In this issue of Clinical Chemistry , Ellervik et al. (1) report relationships between baseline ferritin concentrations and risk of all-cause and cause-specific mortality in 8988 individuals enrolled in the Copenhagen City Heart Study. Median follow-up was 23 years, during which 6364 individuals died. Multifactorially adjusted hazard ratios for total mortality in individuals with ferritin values below vs above 200 μg/L showed significantly lower mortality overall ( P = 0.0008) and separately for men ( P = 0.02) and women ( P = 0.03) with lower ferritin concentrations. Cause-specific mortality below vs above the 200 μg/L threshold was significantly lower for cancer ( P = 0.005), metabolic disease ( P = 0.002) and cardiovascular disease ( P = 0.00006). A highly significant progressive decrease in median survival occurred with increasing ferritin concentrations. The hazard ratio for total mortality increased by 13% for each 100 μg/L increase in ferritin concentration. The median survival was 79 years with concentrations <200 μg/L, 76 years with ferritin concentrations between 200 and 399 μg/L, 72 years with ferritin concentrations between 400 and 599 μg/L, and 55 years with ferritin concentrations in excess of 600 μg/L. A stepwise increase in mortality with increasing ferritin concentrations was found for each disease category. Adjusted hazard ratios for increased disease-specific mortality for ferritin concentrations above 600 μg/L vs below 200 μg/L were significant for malignant ( P = 0.01), endocrine ( P = 0.0001), and cardiovascular ( P = 0.01) disease. The conclusion was that “increased ferritin concentrations represent a biological biomarker predictive of early death in a dose-dependent linear manner in the general population.” Increased ferritin concentrations were interpreted by the authors “as a biological marker of pathogenic processes that reflects severity and presence of a variety of disease states leading to premature death.” They stated that “causality may be …

Iron deficiency in the first 6 months of age in infants born between 32 and 37 weeks of gestational age.

Preterm infants are at risk of iron deficiency (ID). In the Netherlands, preterm infants born after 32 weeks of gestational age (GA) do not receive iron supplementation on a routine basis. We hypothesized that dietary iron intake in these infants might not be sufficient to meet the high iron requirements during the first 6 months of life. In a prospective cohort study, we analyzed the prevalence and risk factors of ID in 143 infants born between 32+0 and 36+6 weeks GA who did not receive iron supplementation. ID at the age of 4 and 6 months was present in 27 (18.9%) and 7 (4.9%) infants. Results of a multivariable logistic regression analysis showed that ID was associated with lower birth weight, a shorter duration of formula feeding, more weight gain in the first 6 months of life and lower ferritin concentrations at the age of 1 week. Preterm infants born after 32 weeks GA have an increased risk of ID compared with those born at term, supporting the need of iron supplementation. Our results suggests that measurement of ferritin at the age of 1 week might be useful to identify those infants at particular risk and could be used in populations without general supplementation programs. However, the efficacy and safety of individualized iron supplementation, based on ferritin concentrations at the age of 1 week, together with other predictors of ID, needs to be further investigated, preferably in a randomized controlled trial.

Sex-specific Profiles of Blood Metal Levels Associated with Metal-Iron Interactions.

The mechanisms by which iron is absorbed are similar to those of divalent metals, particularly manganese, lead, and cadmium. These metals, however, show different toxicokinetics in relation to menarche or menopause, although their interaction with iron is the same. This review focuses on the kinetics of these three toxic metals (manganese, lead, and cadmium) in relation to menarche, pregnancy, and menopause. The iron–manganese interaction is the major factor determining sex-specific differences in blood manganese levels throughout the whole life cycle. The effects of estrogen overshadow the association between iron deficiency and increased blood lead concentrations, explaining why women, despite having lower ferritin concentrations, have lower blood lead concentrations than men. Iron deficiency is associated with elevated cadmium levels in premenopausal women, but not in postmenopausal women or men; these findings indicate that sex-specific differences in cadmium levels at older ages are not due to iron–cadmium interactions, and that further studies are required to identify the source of these differences. In summary, the potential causes of sex-specific differences in the blood levels of manganese, lead, and cadmium differ from each other, although all these three metals are associated with iron deficiency. Therefore, other factors such as estrogen effects, or absorption rate as well as iron deficiency, should be considered when addressing environmental exposure to toxic metals and sex-specific differences in the blood levels of these metals.

Iron Status and Helicobacter pylori Infection in Symptomatic Children: An International Multi-Centered Study

ObjectiveIron deficiency (ID) and iron deficiency anaemia (IDA) are global major public health problems, particularly in developing countries. Whilst an association between H. pylori infection and ID/IDA has been proposed in the literature, currently there is no consensus. We studied the effects of H. pylori infection on ID/IDA in a cohort of children undergoing upper gastrointestinal endoscopy for upper abdominal pain in two developing and one developed country.MethodsIn total 311 children (mean age 10.7±3.2 years) from Latin America - Belo Horizonte/Brazil (n = 125), Santiago/Chile (n = 105) - and London/UK (n = 81), were studied. Gastric and duodenal biopsies were obtained for evaluation of histology and H. pylori status and blood samples for parameters of ID/IDA.ResultsThe prevalence of H. pylori infection was 27.7% being significantly higher (p<0.001) in Latin America (35%) than in UK (7%). Multiple linear regression models revealed H. pylori infection as a significant predictor of low ferritin and haemoglobin concentrations in children from Latin-America. A negative correlation was observed between MCV (r = −0.26; p = 0.01) and MCH (r = −0.27; p = 0.01) values and the degree of antral chronic inflammation, and between MCH and the degree of corpus chronic (r = −0.29, p = 0.008) and active (r = −0.27, p = 0.002) inflammation.ConclusionsThis study demonstrates that H. pylori infection in children influences the serum ferritin and haemoglobin concentrations, markers of early depletion of iron stores and anaemia respectively.

No cross-sectional and longitudinal association of ferritin and symptoms of attention-deficit-/hyperactivity disorder in a large population-based sample of children: results from the GINIplus and LISAplus studies

Attention-deficit/hyperactivity disorder (ADHD) has been associated with alterations in iron metabolism, and low ferritin concentrations in peripheral blood have inconsistently been reported in clinically referred samples of children with ADHD. This study examined whether higher peripheral concentrations of ferritin, the major iron storage protein, are associated with decreased symptoms of ADHD in 2,805 children aged 10 years participating in two large population-based birth cohorts (GINIplus and LISAplus). Whether high ferritin concentrations at age 4 months predict lower ADHD symptoms at age 10 years was also investigated using a longitudinal approach in a subsample of 193 children. No indications for an association between peripheral ferritin concentrations and ADHD symptoms were found in this large population-based study. Re-evaluating iron substitution as a therapeutic measure for ADHD may be warranted.

Increased gastric IL-1β concentration and iron deficiency parameters in H. pylori infected children.

Association between H. pylori infection, iron deficiency and iron deficiency anaemia has been described, but the mechanisms involved have not been established. We hypothesized that in H. pylori infected children increased gastric concentrations of IL-1β and/or TNF-α, both potent inhibitors of gastric acid secretion that is essential for iron absorption, are predictors for low blood concentrations of ferritin and haemoglobin, markers of early depletion of iron stores and anaemia, respectively. We evaluated 125 children undergoing endoscopy to clarify the origin of gastrointestinal symptoms. Gastric specimens were obtained for H. pylori status and cytokine evaluation and blood samples for determination of iron deficiency/iron deficiency anaemia parameters and IL1 cluster and TNFA polymorphisms that are associated with increased cytokine secretions. Higher IL-1β and TNF-α gastric concentrations were observed in H. pylori-positive (n = 47) than in -negative (n = 78) children. Multiple linear regression models revealed gastric IL-1β, but not TNF-α, as a significant predictor of low ferritin and haemoglobin concentrations; results were reproduced in young children in whom IL1RN polymorphic genotypes associated with higher gastric IL-1β expression and lower blood ferritin and haemoglobin concentrations. In conclusion, high gastric levels of IL-1β can be the link between H. pylori infection and iron deficiency/iron deficiency anaemia in childhood.