Low Serum Ferritin Concentration Research Articles

Correlation of serum ferritin and thyroid hormone levels: A matched case–control study

Introduction: Hypothyroidism is a common disorder of the endocrine system caused by insufficient biologically active hormones at the tissue level or the inability of the tissue to utilize thyroid hormones. Iron plays a crucial role in the synthesis and metabolism of thyroid hormones, and it is stored in the body as ferritin. We aimed to evaluate the correlation between serum ferritin (SF) levels and thyroid hormone panel levels in both hypothyroid and euthyroid subjects. Methods: In 2022, a matched case–control study was conducted. The study involved participants with hypothyroidism and a control group (n = 53). The levels of thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), and SF were measured using the chemiluminescence immunoassay on a Mindray Cl 900-i analyzer (Shenzhen Mindray Bio-Medical Electronics Co., China). Results: The hypothyroid group had TSH levels that were significantly higher (10.76 [8.54-18.76] vs. 1.76 [1.26-2.58]; p < 0.001) and SF concentrations that were significantly lower (39.08 [21.15-45.70] vs. 54.09 [41.41-71.82]; p < 0.001) compared to the control group. In both male and female subjects of the hypothyroid group, a strong negative correlation was found between SF concentration and TSH levels ([Rho = −0.855,p < 0.01]; [Rho = −0.747; p < 0.01]). In female subjects of the hypothyroid group, a weak positive correlation was found between SF concentration and fT3 (Rho = 0.488; p < 0.05). In the euthyroid group, a correlation of the same strength and direction was found for fT4 (Rho = 0.366; p < 0.05). Conclusion: Research results indicate a correlation between lower SF concentrations and hypothyroidism, which is of particular importance for understanding the etiopathogenesis, diagnosis, monitoring, and treatment modalities of patients with hypothyroidism.

Association between Body Iron Status and Cognitive Task Performance in a Nationally Representative Sample of Older Adults.

Iron is an essential micronutrient that is necessary for proper cognitive function. However, the dose-response relationship between body iron status and cognitive function remains unclear. The objective of this study was to investigate the association between serum ferritin concentrations, an indicator of body iron status, and cognitive function in older adults. Based on the National Health and Nutrition Examination Survey (NHANES) 1999 -2002 in the United States, nationally representative data was collected from 2,567 adults aged 60 years and older who had objectively measured serum ferritin levels and cognitive performance. High ferritin levels were defined as a serum ferritin level >200 ng/mL in women and >300 ng/mL in men. Low ferritin levels were defined as a serum ferritin level <30 ng/mL. The digit symbol substitution test (DSST) was employed to assess cognitive function. Multivariable logistic regression analyses with survey weights were performed after the DSST was dichotomized at the median score. The weighted prevalence of adults with normal, low, and high serum ferritin levels were 73.98%, 9.12%, and 16.91%, respectively. A U-shaped association between serum ferritin concentrations and cognitive task performance was observed. After adjusting for demographic, socioeconomic, lifestyle, and C-reactive protein factors, the odds ratio (95% confidence intervals) for lower cognitive performance was 1.39 (1.11, 1.74) in adults with high ferritin levels and 1.38 (0.86, 2.22) in adults with low ferritin levels, compared with those with normal ferritin levels. The association between serum ferritin levels and lower cognitive performance was stronger in adults aged 60 to 69 years old than those aged 70 years and older. In conclusion, in a nationally representative sample of older adults in the United States, a high serum ferritin level was significantly associated with worse cognitive task performance. Thus, the relationship between low serum ferritin concentrations and cognitive task performance warrants further investigation.

Implication of asymptomatic and clinical Plasmodium falciparum infections on biomarkers of iron status among school-aged children in Malawi

BackgroundIron status is considered as a continuum from an iron deficiency with anaemia, without anaemia, varying amounts of stored iron to iron overload. The burden of Plasmodium falciparum infections is typically high among school-aged children (SAC). Nonetheless, SAC are often less likely to be covered by malaria interventions, making them a group with an untreated reservoir of parasite transmission. This study aimed to assess the effects of asymptomatic and clinical malaria infections on biochemical markers of iron status among SAC in Malawi.MethodsData from the 2015–2016 Malawi Micronutrient Survey (MNS) was used and multivariable logistic regression models using a generalized estimating equation to account for the complex cluster survey design were constructed. Blood samples of 684 children aged 5 to 14 years old were evaluated for clinical and asymptomatic malaria infections. Furthermore, blood samples were used to estimate haemoglobin (Hb), serum ferritin (SF) and, soluble transferrin receptors (sTfR) concentrations.ResultsOf the 684 SAC analysed, approximately 42% had asymptomatic malaria, while 41.0% had clinical malaria. Anaemia (low Hb levels), iron deficiency (low SF concentration), and functional iron deficiency (high sTfR levels) were found in 20%, 5%, and 30% of the children, respectively. School-aged children with asymptomatic malaria had increased odds of being anaemic (adjusted odds ratio [aOR]: 3.71, 95% confidence interval [CI]: 2.29–5.99) and increased levels of sTfR (aOR: 3.00, 95% CI 2.01–4.47). Similarly, SAC with clinical malaria had increased odds of being anaemic (aOR: 3.54, 95% CI 2.19–5.72) and increased levels of sTfR (aOR: 3.02, 95% CI 2.02–4.52).ConclusionsBoth asymptomatic and clinical malaria were independent risk factors for anaemia and functional iron deficiency (FID). The notion that asymptomatic and clinical malaria were associated with both anaemia and FID underscores the need for public health programmers to consider adding mass screening and treatment for malaria to existing school-based health programmes.

Health status of patients with β-thalassemia in the West Bank: a retrospective study

BackgroundThe management of β-thalassemia in developing countries is challenging due to few treatments being available other than recurrent transfusions. We assessed the haematological, biochemical, and hormonal findings among patients with β-thalassemia in the West Bank, occupied Palestinian territory. MethodsThis retrospective study was done between Jan 1, 2017, and Dec 31, 2018. Data on haematological, biochemical, and hormonal tests were collected from medical files of patients with β-thalassemia in eight primary health-care clinics, nine emergency departments, and eleven Palestinian Ministry of Health hospitals across the West Bank. Additionally, we collected data on demographics and the use of iron chelation. The study was approved by the research ethics committee at Al-Quds University and the Palestinian Ministry of Health (reference 162/1075/2019). The data had no identifying information and, therefore, informed consent from patients was waived for this study. Findings309 patients with β-thalassemia were included in the study (154 men and 155 women), with an average age of 23·4 (SD 10·4) years. 202 (79%) patients had pretransfusion haemoglobin concentrations lower than 9 g/dL (mean 8·4 [SD 1·4]). Additionally, 185 (73%) had iron overload, with the mean ferritin concentration in serum being 3175·8 μg/L (SD 3378·8). Concentrations of alanine aminotransferase and aspartate aminotransferase were high in 91 (38%) and 145 (61%) patients, respectively, and correlated positively with serum ferritin concentrations (r=0·527 and r=0·254, respectively; both p<0·0001). Kidney function tests (serum creatinine and blood urea nitrogen) did not correlate with serum ferritin (p=0·553 and 0·280, respectively). Deferoxamine was used for iron chelation in 63 (27%), and these patients had significantly higher ferritin concentrations in serum than patients receiving deferasirox (175 [74%], p=0·009). A small proportion of patients had endocrine function data that indicated abnormal total tri-iodothyronine, free thyroxine, and thyroid-stimulating hormone levels in 24 (34%), 29 (37%), and 24 (15%) patients, respectively, in addition to abnormal parathyroid hormone levels in 25 (50%) patients. However, these findings were not sufficient to diagnose or interpret endocrinopathies. InterpretationOur findings showed a lack of adherence to international guidelines in the management of β-thalassemia, which was reflected by the low pretransfusion haemoglobin and high serum ferritin concentrations. This study highlights the importance of establishing patient-tailored comprehensive assessment and follow-up protocols for the management of β-thalassemia with an emphasis on blood transfusion and iron chelation practices. FundingNone.

Physiologically based serum ferritin thresholds for iron deficiency in women of reproductive age who are blood donors

AbstractOur objective is to develop a physiologically based method to determine serum ferritin thresholds for iron deficiency in healthy individuals. The current World Health Organization threshold of <15 µg/L for iron deficiency in women is based on expert opinion. We examined the relationship between serum ferritin and 2 independently measured indicators of iron-deficient erythropoiesis, soluble transferrin receptor (sTfR) and hemoglobin, in baseline data from 286 women, 20 to 49 years, who were first-time or reactivated donors in the Retrovirus Epidemiology Donor Study-II Donor Iron Status Evaluation (REDS-RISE) study. At lower serum ferritin concentrations, median sTfR increased as hemoglobin decreased. Using restricted cubic spline regression analysis to determine thresholds for iron-deficient erythropoiesis, the thresholds identified by sTfR (serum ferritin < 25.4 µg/L) and hemoglobin (serum ferritin < 25.3 µg/L) did not differ significantly. The thresholds found in the REDS-RISE study do not differ from those identified by sTfR (serum ferritin < 25.5 µg/L) and hemoglobin (serum ferritin < 26.6 µg/L) in a previous study of 5442 women, 20 to 49 years, in the US National Health and Nutrition Examination Survey 2003 to 2018 (P = .98 and 0.83, respectively). Although international comparisons are needed, these results with US data provide additional evidence for the potential usefulness of a physiologically based method to identify serum ferritin thresholds for iron deficiency.

Physiologically based serum ferritin thresholds for iron deficiency in children and non-pregnant women: a US National Health and Nutrition Examination Surveys (NHANES) serial cross-sectional study

Serum ferritin concentrations are the most widely used indicator for iron deficiency. WHO determined that insufficient data are available to revise the serum ferritin thresholds of less than 12 μg/L for children and less than 15 μg/L for women, which were developed on the basis of expert opinion, to define iron deficiency. We aimed to derive new physiologically based serum ferritin concentration thresholds for iron deficiency in healthy young children and non-pregnant women using data from the US National Health and Nutrition Examination Survey (NHANES). In this serial cross-sectional study, we examined the relationship of serum ferritin with two independent indicators of iron-deficient erythropoiesis, haemoglobin and soluble transferrin receptor (sTfR), in children (12-59 months) and non-pregnant women (15-49 years) using cross-sectional NHANES data from 2003-06, 2007-10, and 2015-18. NHANES is a US national stratified multistage probability sample that includes a household interview followed by a standardised physical examination in a mobile examination centre. We excluded individuals with missing serum ferritin, sTfR, haemoglobin, or white blood cell counts measurements; non-pregnant women with missing C-reactive protein (CRP), alanine aminotransferase (ALT) or aspartate aminotransferase (AST) data were also excluded. In addition, individuals with infection (white blood cell counts >10·0×109/L) and non-pregnant women with possible liver disease (ALT >70 IU/L or AST >70 IU/L) and inflammation (CRP >5·0 mg/L) were excluded. We examined distributions of haemoglobin and sTfR with serum ferritin and used restricted cubic spline regression models to determine serum ferritin thresholds for iron-deficient erythropoiesis. 5964 children and 10 462 non-pregnant women had physical examinations and were screened for inclusion in the study, of whom 2569 (43·1%) children and 7498 (71·7%) non-pregnant women were included. At lower serum ferritin concentrations, median haemoglobin concentration decreased as sTfR concentration increased, with each varying in a curvilinear manner. Using restricted cubic spline plateau points to determine the onset of iron-deficient erythropoiesis, the serum ferritin thresholds identified by haemoglobin and sTfR concentrations were not different. For children, the haemoglobin identified serum ferritin threshold was 19·9 μg/L (95% CI 18·8-22·6) and the sTfR identified serum ferritin threshold was 20·0 μg/L (19·4-20·9; p=0·89). For women the haemoglobin identified serum ferritin threshold was 25·2 μg/L (24·2-26·2) and the sTfR identified serum ferritin threshold was 24·0 μg/L (23·3-24·6; p=0·05). The association between two independent indicators of iron-deficient erythropoiesis, haemoglobin and sTfR, identified serum ferritin concentration thresholds of about 20 μg/L for children and 25 μg/L for non-pregnant women, providing physiological evidence of potential new thresholds for consideration when determining the prevalence and distribution of iron deficiency in populations. In healthy children and non-pregnant women, physiologically based thresholds for iron deficiency might be more clinically and epidemiologically relevant than those based on expert opinion. Validation of this physiologically based approach in non-US populations might help the international harmonisation of serum ferritin thresholds for iron deficiency. None.

Predictive Value of Serum Ferritin in Combination with Alanine Aminotransferase and Glucose Levels for Noninvasive Assessment of NAFLD: Fatty Liver in Obesity (FLiO) Study.

The identification of affordable noninvasive biomarkers for the diagnosis and characterization of nonalcoholic fatty liver disease (NAFLD) is a major challenge for the research community. This study aimed to explore the usefulness of ferritin as a proxy biomarker of NAFLD condition, alone or in combination with other routine biochemical parameters. Subjects with overweight/obesity and ultrasound-confirmed liver steatosis (n = 112) from the Fatty Liver in Obesity (FLiO) study were assessed. The hepatic evaluation considered magnetic resonance imaging, ultrasonography, and credited routine blood liver biomarkers. Anthropometry and body composition, dietary intake (by means of a validated 137-item food frequency questionnaire), and specific biochemical markers were also determined. Serum ferritin levels were analyzed using a chemiluminescent microparticle immunoassay kit. Lower serum ferritin concentrations were associated with general better liver health and nutritional status. The evaluation of ferritin as a surrogate of liver damage by means of quantile regression analyses showed a positive association with alanine aminotransferase (ALT) (β = 19.21; p ≤ 0.001), liver fat content (β = 8.70; p = 0.008), and hepatic iron (β = 3.76; p ≤ 0.001), after adjusting for potential confounders. In receiver operating characteristic (ROC) analyses, the panel combination of blood ferritin, glucose, and ALT showed the best prediction for liver fat mass (area under the curve (AUC) 0.82). A combination of ferritin and ALT showed the higher predictive ability for estimating liver iron content (AUC 0.73). This investigation demonstrated the association of serum ferritin with liver health as well as with glucose and lipid metabolism markers in subjects with NAFLD. Current findings led to the identification of ferritin as a potential noninvasive predictive biomarker of NAFLD, whose surrogate value increased when combined with other routine biochemical measurements (glucose/ALT).

Serum hepcidin concentrations in relation to iron status in children with type 1 diabetes

Chronic low-grade inflammation in type 1 diabetes (T1D) might increase hepcidin synthesis, possibly resulting in functional iron deficiency (FID). We hypothesized that in T1D children with FID, hepcidin concentrations are increased compared to those with normal iron status and those with absolute iron deficiency (AID). We evaluated hepcidin concentrations in T1D children in relation to iron status, and investigated whether hepcidin is useful in assessing FID. A cross-sectional study was conducted. FID was defined as elevated zinc protoporphyrin/heme ratio and/or red blood cell distribution width, and AID as low serum ferritin concentration. Post-hoc analyses with different definitions of FID were performed, using transferrin saturation and reticulocyte hemoglobin content. Serum hepcidin concentrations were measured using mass-spectrometry. The IRODIAB-study is registered at www.trialregister.nl (NTR4642). This study included 215 T1D children with a median age of 13.7 years (Q1–Q3: 10.1–16.3). The median (Q1–Q3) hepcidin concentration in patients with normal iron status was 1.8 nmol/l (0.9–3.3), in AID-patients, 0.4 nmol/l (0.4–0.4) and in FID-patients, 1.6 nmol/l (0.7–3.5). Hepcidin concentrations in FID-patients were significantly higher than in AID-patients (p < 0.001). Irrespective of FID-definition used, hepcidin concentrations did not differ between FID-patients and patients with normal iron status. This might be explained by the influence of various factors on hepcidin concentrations, and/or by differences in response of iron parameters over time. Single hepcidin measurements do not seem useful in assessing FID in T1D children. Multiple hepcidin measurements over time in future studies, however, might prove to be more useful in assessing FID in children with T1D.

Dietary Iron Bioavailability: A Simple Model That Can Be Used to Derive Country-Specific Values for Adult Men and Women.

Reference intakes for iron are derived from physiological requirements, with an assumed value for dietary iron absorption. A new approach to estimate iron bioavailability, calculated from iron intake, status, and requirements was used to set European dietary reference values, but the values obtained cannot be used for low- and middle-income countries where diets are very different. We aimed to test the feasibility of using the model developed from United Kingdom and Irish data to derive a value for dietary iron bioavailability in an African country, using data collected from women of child-bearing age in Benin. We also compared the effect of using estimates of iron losses made in the 1960s with more recent data for whole body iron losses. Dietary iron intake and serum ferritin (SF), together with physiological requirements of iron, were entered into the predictive model to estimate percentage iron absorption from the diet at different levels of iron status. The results obtained from the 2 different methods for calculating physiological iron requirements were similar, except at low SF concentrations. At a SF value of 30 µg/L predicted iron absorption from the African maize-based diet was 6%, compared with 18% from a Western diet, and it remained low until the SF fell below 25 µg/L. We used the model to estimate percentage dietary iron absorption in 30 Beninese women. The predicted values agreed with results from earlier single meal isotope studies; therefore, we conclude that the model has potential for estimating dietary iron bioavailability in men and nonpregnant women consuming different diets in other countries.

The Effect of Serum 25-Hydroxyvitamin D on Serum Ferritin Concentrations: A Longitudinal Study of Participants of a Preventive Health Program.

Various studies have suggested a role of vitamin D in inflammation. However, its effect on ferritin, a biomarker of inflammation, has received relatively little attention. Therefore, we aimed to assess the association of serum 25-hydroxyvitamin D (25(OH)D) with serum ferritin (SF) concentrations, and to examine whether temporal increases in serum 25(OH)D concentrations are paralleled by a reduction in SF concentrations. Data from a community sample of Canadian adults who participated in a preventive health program (n = 6812) were analyzed. During the follow-up, serum 25(OH)D concentrations increased from 80.7 to 115.0 nmol/L whereas SF concentrations decreased from 122.0 to 92.0 µg/L (median follow-up time was 11.67 months). Cross-sectional analyses revealed that compared to participants with 25(OH)D concentrations of <50 nmol/L, those with 25(OH)D concentrations of 75 to <100, 100 to <125, and ≥125 nmol/L had SF concentrations that were 13.00, 23.15, and 27.59 µg/L lower respectively (p < 0.001). Compared to those without temporal improvements in 25(OH)D concentrations between baseline and follow-up, participants who improved their 25(OH)D concentrations with ≥50 nmol/L decreased their SF concentrations with 5.71 µg/L. For participants for whom the increase in 25(OH)D concentrations was less than 50 nmol/L, decreases in SF concentrations were less pronounced and not statistically significant. These observations suggest that despite strong associations between 25(OH)D and SF concentrations, interventions aiming to lower SF concentrations through sun-exposure and vitamin D supplementation should target substantial increases in 25(OH)D concentrations.

Effect of Oral Iron Administration on Mental State in Children With Low Serum Ferritin Concentration.

Serum ferritin is an iron-binding protein and is the target of the most sensitive and specific tests used for the identification of iron deficiency.1,2 In recent years, serum ferritin levels <30 ng/mL were considered to indicate iron deficiency even if the hemoglobin (Hb) content was within the reference range. In clinical practice, it is recommended that individuals with serum ferritin levels <40 ng/mL are considered iron deficient.1 In the field of pediatrics and child psychiatry, reduced serum ferritin is known to be associated with sleep disorder due to restless legs syndrome (RLS),3 attention-deficit/hyperactivity disorder,4 and tic severity.5 For RLS, iron administration is recommended when serum ferritin is <50 ng/mL.3 However, few studies have focused on serum ferritin itself to investigate the effect of reduced serum ferritin on psychological and physical symptoms of children. This study evaluated psychiatric features of children with reduced serum ferritin concentration and elucidated the effect of iron administration on the psychological and physical symptoms of the children who visited outpatient clinic.

Effects of deferasirox dose and decreasing serum ferritin concentrations on kidney function in paediatric patients: an analysis of clinical laboratory data from pooled clinical studies

Serious and fatal deferasirox-induced kidney injury has been reported in paediatric patients. This study aimed to investigate the effects of deferasirox dose and serum ferritin concentrations on kidney function and the effect of impaired kidney function on dose-normalised deferasirox minimum plasma concentration (Cmin). We did a case-control analysis using pooled data from ten clinical studies. We identified transfusion-dependent patients with thalassaemia, aged 2-15 years, who were receiving deferasirox and had available baseline and follow-up serum creatinine and ferritin measurements. Cases of acute kidney injury (AKI) were defined according to an estimated glomerular filtration rate (eGFR) threshold of 90 mL/min per 1·73 m2 or less (if baseline eGFR was ≥100 mL/min per 1·73 m2), an eGFR of 60 mL/min per 1·73 m2 or less (if baseline eGFR was <100 mL/min per 1·73 m2), or an eGFR decrease from baseline of at least 25%. Cases were matched to control visits (eGFR ≥120 mL/min per 1·73 m2) on age, sex, study site, and time since drug initiation. We calculated rate ratios for AKI using conditional logistic regression, and evaluated the effect of eGFR changes on Cmin. Among 1213 deferasirox-treated paediatric patients, 162 cases of AKI and 621 matched control visits were identified. Patients with AKI had a mean 50·2% (SD 15·5) decrease in eGFR from baseline, compared with a 6·9% (29·8) decrease in controls. A significantly increased risk for AKI (rate ratio 1·26, 95% CI 1·08-1·48, p=0·00418) was observed per 5 mg/kg per day increase in deferasirox dispersible tablet dose (equivalent to a 3·5 mg/kg per day dose of film-coated tablets or granules), above the typical starting dose (20 mg/kg per day). An increased risk (1·25, 1·01-1·56, p=0·0400) for AKI was also observed per 250 μg/L decrease in serum ferritin, starting from 1250 μg/L. High-dose deferasirox (dispersible tablet dose >30 mg/kg per day) resulted in an increased risk (4·47, 1·25-15·95, p=0·0209) for AKI when serum ferritin was less than 1000 μg/L. Decreases in eGFR were associated with increased Cmin. Deferasirox can cause AKI in a dose-dependent manner. The increased AKI risk with high-dose deferasirox and lower serum ferritin concentration is consistent with overchelation as a causative factor. Small decreases in eGFR correlate with increased deferasirox Cmin, especially in younger patients. Physicians should closely monitor renal function and serum ferritin, use the lowest effective dose to maintain acceptable body iron burden, and interrupt deferasirox treatment when AKI or volume depletion are suspected. None.

Correction: Iron deficiency associates with deterioration in several symptoms independently from hemoglobin level among chronic hemodialysis patients.

[This corrects the article DOI: 10.1371/journal.pone.0201662.].

Iron deficiency associates with deterioration in several symptoms independently from hemoglobin level among chronic hemodialysis patients

BackgroundWhile iron deficiency (ID) is a frequent cause of anemia in hemodialysis patients, the clinical impact of ID without anemic level of hemoglobin remains unclear. As such, this study was designed to clarify the manifestations of ID itself in subjects on hemodialysis.MethodsMaintenance hemodialysis patients achieving target hemoglobin levels (≥ 10.0g/dL) under treatment in our clinic were stratified for comparison from three perspectives: ID (transferrin saturation [TSAT] < 20% or ferritin < 100ng/mL) vs non-ID, level of TSAT (< or ≥ 20%), and level of serum ferritin concentration (< or ≥ 100ng/mL). The severity of frequent symptoms was determined by a self-rating symptom score questionnaire, and the rate of those with severe manifestations was calculated for each symptom. Significant difference was examined between groups; univariate and adjusted multivariate odds ratios and 95% confidence intervals were obtained by logistic regression.ResultsAmong 154 subjects selected for analysis, the ratio of severe arthralgia and fatigue was significantly higher in the ID group (n = 94) compared to the non-ID group (n = 60), in both univariate and adjusted multivariate analyses. Moreover, in multivariate analysis, low TSAT was significantly associated with exacerbation of pain during vascular access puncture and intradialytic leg cramps, while low serum ferritin concentration was related to significant increase in severe arthralgia, fatigue, intradialytic headache and leg cramps.ConclusionsID was identified as a risk factor regarding severity of several symptoms even without low hemoglobin level among chronic hemodialysis patients, and supplementation of iron was considered efficacious for improving critical symptoms affecting those undergoing maintenance dialysis.

Serum ferritin as an indicator of iron status: what do we need to know?

Determination of iron status in pregnancy and in young children is essential for both clinical and public health practice. Clinical diagnosis of iron deficiency (ID) through sampling of bone marrow to identify the absence of body iron stores is impractical in most cases. Serum ferritin (SF) concentrations are the most commonly deployed indicator for determining ID, and low SF concentrations reflect a state of iron depletion. However, there is considerable variation in SF cutoffs recommended by different expert groups to diagnose ID. Moreover, the cutoffs used in different clinical laboratories are heterogeneous. There are few studies of diagnostic test accuracy to establish the sensitivity and specificity of SF compared with key gold standards (such as absent bone marrow iron stores, increased intestinal iron absorption, and hemoglobin response to SF) among noninflamed, outpatient populations. The limited data available suggest the commonly recommended SF cutoff of <15 μg/L is a specific but not sensitive cutoff, although evidence is limited. Data from women during pregnancy or from young children are especially uncommon. Most data are from studies conducted >30 y ago, do not reflect ethnic or geographic diversity, and were performed in an era for which laboratory methods no longer reflect present practice. Future studies to define the appropriate SF cutoffs are urgently needed and would also provide an opportunity to compare this indicator with other established and emerging iron indexes. In addition, future work would benefit from a focus on elucidating cutoffs and indexes relevant to iron adequacy.

Randomized controlled trial assessing the efficacy of a reusable fish-shaped iron ingot to increase hemoglobin concentration in anemic, rural Cambodian women

Background: Anemia affects 45% of women of childbearing age in Cambodia. Iron supplementation is recommended in populations in which anemia prevalence is high. However, there are issues of cost, distribution, and adherence. A potential alternative is a reusable fish-shaped iron ingot, which, when added to the cooking pot, leaches iron into the fluid in which it is prepared.Objective: We sought to determine whether there was a difference in hemoglobin concentrations in rural Cambodian anemic women (aged 18-49 y) who cooked with the iron ingot or consumed a daily iron supplement compared with a control after 1 y.Design: In Preah Vihear, 340 women with mild or moderate anemia were randomly assigned to 1) an iron-ingot group, 2) an iron-supplement (18 mg/d) group, or 3) a nonplacebo control group. A venous blood sample was taken at baseline and at 6 and 12 mo. Blood was analyzed for hemoglobin, serum ferritin, and serum transferrin receptor. Hemoglobin electrophoresis was used to detect structural hemoglobin variants.Results: Anemia prevalence was 44% with the use of a portable hemoglobinometer during screening. At baseline, prevalence of iron deficiency was 9% on the basis of a low serum ferritin concentration. There was no significant difference in mean hemoglobin concentrations between the iron-ingot group (115 g/L; 95% CI: 113, 118 g/L; P = 0.850) or iron-supplement group (115 g/L; 95% CI: 113, 117 g/L; P = 0.998) compared with the control group (115 g/L; 95% CI: 113, 117 g/L) at 12 mo. Serum ferritin was significantly higher in the iron-supplement group (73 μg/L; 95% CI: 64, 82 μg/L; P = 0.002) than in the control group at 6 mo; however, this significance was not maintained at 12 mo (73 μg/L; 95% CI: 58, 91 μg/L; P = 0.176).Conclusions: Neither the iron ingot nor iron supplements increased hemoglobin concentrations in this population at 6 or 12 mo. We do not recommend the use of the fish-shaped iron ingot in Cambodia or in countries where the prevalence of iron deficiency is low and genetic hemoglobin disorders are high. This trial was registered at clinicaltrials.gov as NCT02341586.

Modeling tool for calculating dietary iron bioavailability in iron-sufficient adults1–3

Background: Values for dietary iron bioavailability are required for setting dietary reference values. These are estimated from predictive algorithms, nonheme iron absorption from meals, and models of iron intake, serum ferritin concentration, and iron requirements.Objective: We developed a new interactive tool to predict dietary iron bioavailability.Design: Iron intake and serum ferritin, a quantitative marker of body iron stores, from 2 nationally representative studies of adults in the United Kingdom and Ireland and a trial in elderly people in Norfolk, United Kingdom, were used to develop a model to predict dietary iron absorption at different serum ferritin concentrations. Individuals who had raised inflammatory markers or were taking iron-containing supplements were excluded.Results: Mean iron intakes were 13.6, 10.3, and 10.9 mg/d and mean serum ferritin concentrations were 140.7, 49.4, and 96.7 mg/L in men, premenopausal women, and postmenopausal women, respectively. The model predicted that at serum ferritin concentrations of 15, 30, and 60 mg/L, mean dietary iron absorption would be 22.3%, 16.3%, and 11.6%, respectively, in men; 27.2%, 17.2%, and 10.6%, respectively, in premenopausal women; and 18.4%, 12.7%, and 10.5%, respectively, in postmenopausal women.Conclusions: An interactive program for calculating dietary iron absorption at any concentration of serum ferritin is presented. Differences in iron status are partly explained by age but also by diet, with meat being a key determinant. The effect of the diet is more marked at lower serum ferritin concentrations. The model can be applied to any adult population in whom representative, good-quality data on iron intake and iron status have been collected. Values for dietary iron bioavailability can be derived for any target concentration of serum ferritin, thereby giving risk managers and public health professionals a flexible and transparent basis on which to base their dietary recommendations. This trial was registered at clinicaltrials.gov as NCT01754012.

Iron status among Australian adults: findings of a population based study in Queensland, Australia.

To describe the concentrations of serum ferritin among Australian adults by age and sex. Further, the relationships of various social, lifestyle and health factors with serum ferritin concentrations were explored. A total of 1634 adults aged<or=25 years from six randomly selected urban centres in Queensland, Australia participated in the study that was conducted between October and December 2000. Prevalence of depleted iron stores, based on low serum ferritin concentration, was 10.6% among females aged<50 years, 2.8% among females aged<or=50 years and virtually nil among males. In contrast, 16% of the males and 20% of the females aged<or=50 years had elevated se-rum ferritin concentrations. Significantly higher serum ferritin concentrations were found among females of both age groups who consumed alcohol at a rate of >60 drinks/month, and females aged<50 years who were obese. Lower serum ferritin concentrations were found only among females aged<50 years, with higher education attainment. In multivariable analysis, only the association between higher serum ferritin and obesity was consistent across age-sex groups and statistically significant. Iron deficiency may be a problem among Australian females of reproductive age. Further research is needed to identify the determinants of low iron concentrations in younger females and elevated concentrations of serum ferritin in males and older females in order to develop preventive measures.

Impact of maternal, antenatal and birth-associated factors on iron stores at birth: data from a prospective maternal-infant birth cohort.

Low serum ferritin concentrations at birth, which reflect neonatal iron stores, track through to early childhood and have been associated with poorer neurodevelopmental outcomes. We aimed to identify maternal, antenatal and birth-associated factors that influence iron stores at birth in a prospective maternal-infant birth cohort. In a population-based, longitudinal, birth cohort in Ireland, 413 maternal-infant dyads with prospectively collected lifestyle and clinical data from 15 weeks' gestation had umbilical cord serum ferritin concentrations measured. Regression models were developed to identify independent factors associated with cord ferritin concentrations. Median (IQR) cord ferritin concentrations were 185.7 (131.7, 385.5) μg/l, and 8% (n=33) of infants had low iron stores (ferritin <76 μg/l) at birth. Maternal obesity (BMI ⩾30 kg/m2) at 15 weeks' gestation (adj. estimate (95% confidence interval (CI)): -66.4 (-106.9, -25.9) μg/l, P<0.0001) and delivery by caesarean section (-38.8 (-70.2, -7.4) μg/l, P=0.016) were inversely associated with cord ferritin concentrations. In addition, maternal smoking at 15 weeks' gestation (adj. odds ratio (95% CI): 2.9 (1.2, 7), P=0.020) and being born small-for-gestational age (3.4 (1.3, 8.9), P=0.012) were associated with an increased risk of low iron stores (ferritin <76 μg/l) at birth. We have identified a number of potentially modifiable lifestyle factors that influence iron stores at birth, with the important role of overall maternal health and lifestyle during pregnancy highlighted. Public health policies targeting women of child-bearing age to improve nutrition and health outcomes should be prioritised for the health of the next generation.

Effect of Nitrates, Thiocyanates and Selenium on the Iron and Iodine Status of Postpartum Women.

To find correlations between high thiocyanate and nitrate levels and low selenium levels and the indicators of the iodine and iron status of postpartum women. The study included 41 mothers aged 26.4±5.9 yrs from Asenovgrad and nearby villages. Urinary iodine was determined by the Sandell-Kolthoff reaction and thiocyanate - by the interaction of these ions with acidic solution of KMnO4; for serum nitrates we used the colorimetric method; serum selenium was assessed by electro-thermal atomic-absorption spectrophotometry; thyroxin (FT4), the thyroid stimulating hormone (TSH), serum ferritin (SF), and serum transferrin receptor (sTfR) were determined using ELISA; Hb levels were determined by hematology analyzer. Assessing the iodine status, we found a negative correlation between the levels of iodine and thiocyanates in urine (R=-0.717, р<0.0001), a positive correlation between nitrates and TSH (R=0.487, р=0.003) and a negative correlation between nitrates and FT4 (R=-0.312, р=0.06). For the iron status, we found a negative correlation between nitrates and SF (R=-0.429, р=0.009) and between nitrates and Hb (R=-0.383, р=0.021). The Mann-Whitney U-test showed that in women with nitrate levels higher than the mean value there was low FT4 level (р=0.06), high TSH level (р=0.013), low Hb concentration (р=0.061) and low SF concentration (р=0.005). The combined effects of environmental factors (elevated nitrate levels and low selenium level) on the iodine and iron status are manifested by low concentrations of FT4 (р=0.033), Hb (р=0.06) and SF (р=0.05) and high level of TSH (р=0.05). In conclusion, we found that environmental factors, especially when combined, have a negative impact on the iron and iodine status of females.