Measures Of Iron Status Research Articles

Abstract A105: Blood donation in relation to colorectal cancer risk in men

Abstract Background: Excessive iron may increase colorectal cancer risk, as shown in vitro and animal studies. Human observational studies of iron intakes and body iron stores in relation to colorectal cancer risk have been conflicting, which may partly due to non-specific measurement of iron status. We used the lifetime number of blood donation, a validated determinant of serum ferritin, to investigate the iron hypothesis, which has only been examined in one prior study. Serum ferritin is a reliable measure of body iron stores. Thus, the hypothesis of the depletion of body iron stores lowering the colorectal cancer risk can be tested by comparing colorectal cancer risk between regular blood donors and non-donors. Method: We prospectively examined the association between lifetime number of blood donations and colorectal cancer risk in the Health Professionals Follow-up Study. Information on number of blood donation and other colorectal cancer risk factors was obtained in 1992 questionnaire. A Cox proportional hazard regression was used to estimate the multivariable relative risks (RRs, 95%CIs). Results: We documented 659 incident colorectal cancer cases during 16 years of follow-up. The age-adjusted results yielded essentially the same results as the multivariable results. Comparing with the non-donors, the multivariable RRs (95%CIs) were 0.95 (0.79, 1.15) for 1–4 donation, 0.86 (0.65, 1.13) for 5–9 donations, 0.97 (0.73, 1.29) for 10–19 donations, 0.89 (0.60, 1.31) for 20–29 donations, and 1.16 (95%CI: 0.82, 1.63) for at least 30 donations (P-value for test for trend = 0.46). In addition, the null associations did not vary by colorectal cancer sub-sites, or levels of intakes of total iron and heme iron. Conclusion: Lifetime number of blood donation is not associated with risk of developing colorectal cancer risk in men. Our results do not support an important role of body iron stores in colorectal carcinogenesis. Citation Information: Cancer Prev Res 2011;4(10 Suppl):A105.

Iron, Folate, and Vitamin B12 Status in the Elderly by Gender and Ethnicity

ObjectiveNational Health and Nutrition Examination Survey 2001-2002 data were used to examine gender and ethnicity relationships to iron, folate, and vitamin B12 status, and anemia in 1770 elderly persons. MethodsDependent variables included dietary intakes and biochemical measures of iron, folate, and vitamin B12 status, and hemoglobin. t Tests were performed using SUDAAN software (version 9.0; Research Triangle Institute International, Research Triangle Park, North Carolina). The relationships of gender and ethnicity to adequacy of iron, folate, and vitamin B12status, and anemia were investigated using x2 tests. ResultsMales had significantly higher nutrient intakes and better biochemical measures of iron status but lower biochemical measures of folate and vitamin B12. Whites were significantly more likely to have nutrient intakes higher than those recommended by the Food and Nutrition Board. No clear pattern of biochemical measures of iron status was seen among the ethnic groups, and there was no significant relationship between iron status and ethnicity. Biochemical measures of folate status were significantly higher in whites and Mexican Americans than in blacks. No significant relationships were found between folate status and ethnicity. Mean serum vitamin B12 was significantly higher in blacks than in whites and was lowest in other Hispanics who were significantly more likely to be vitamin B12 deficient. Blacks had significantly lower mean hemoglobin values than whites and were significantly more likely to be anemic. ConclusionsBased on biochemical measures, elderly males are at higher risk of folate and vitamin B12 deficiencies. Ethnicity was not significantly related to either iron or folate status. Other Hispanics were significantly more likely to be vitamin B12 deficient.

P2-351 Iron status and cardiovascular disease risk in black South African women: the pure study

ObjectiveTo examine the associations between measures of iron status and cardiovascular disease (CVD) risk factors in South African women.DesignThe study was cross-sectional in design. Demographic information and health history were...

The effect of consuming biofortified beans on the iron status of Mexican school children

Advances in plant breeding have resulted in a 73% increase in the iron content of black bean varieties similar to those consumed in Mexico. The efficacy of consuming these biofortified beans was tested in 587 primary school children in the Mexican state of Oaxaca. We randomized 20 schools to consume either biofortified (95mg/kg Fe) or control beans (55mg/kg Fe) for 110 days. At baseline 137 children (24%) were iron depleted with serum ferritin <20μg/L, and 18% were anemic (Hb<110g/L). Children consumed an average of 11 kg beans during the trial and the high iron bean group consumed an estimated additional 18% of their RI for iron. Children in the high iron bean group had significantly greater reduction in transferrin receptor (TfR) from baseline to end line compared to the low iron group (p<.001). The more iron deficient subjects (high baseline TfR) experience the greatest group difference in change of TfR (p=.05) compared to subjects with lower baseline TfR (interaction of baseline TfR by bean group, p=.011). The greatest group difference in improvement in TfR was also seen in children who consumed the most beans throughout the feeding trial. Interpretation of change in ferritin values appears to be complicated by differential rates of infections in the 2 groups. We conclude that consuming beans that are bred for enhanced iron content improves selected measures of iron status in school children. Supported by HarvestPlus

Assessment of iron deficiency in Kenyan children from capillary blood

In absence of a non-invasive gold standard, iron deficiency anemia (IDA) stages are best characterized by multi-indices. However, choice of an appropriate single iron biomarker to replace multi-criteria model for ID screening in resource poor settings is of critical need. We compared ID defined as ¡Ý2 of 3 abnormal values in ferritin (SF), transferrin receptor (sTfR), or zinc protoporphyrin (ZP) concentrations (i.e. multi-criteria model) to ID defined by abnormal levels in any of iron biomarkers (SF alone, or sTfR alone, or ZP alone). This was a cross-sectional survey. Capillary blood was obtained from 680 children (aged 6C35 mo) for measurement of iron status using SF, sTfR, and ZP. Based on multi-criteria model, ID prevalence (¡ÀSE) was 62.1¡À1.9%, whilst those based on abnormal values in SF, sTfR, and ZP, were 40.0¡À1.9%, 57.7¡À1.9%, and 77.3¡À1.6%, respectively. The қ statistics for agreement between multi-criteria model and other iron indicators were 0.5 to 0.8; with sTfR having the best agreement (қ=0.84). Receiver-operating characteristic (ROC) curve analysis showed sTfR (area-under-the-curve (AUC) = 0.69) to be superior to both SF (AUC=0.61) and ZP (AUC=0.63) in predicting IDA (p<0.001). sTfR, compared to SF and ZP, accurately estimates the prevalence of ID in children based on multi-indices and least affected by inflammation. Funded by CDC and Nevin Scrimshaw International Nutrition Foundation. Grant Funding Source: NUTRITION (ASN)

Haptoglobin genotype and the iron hypothesis of atherosclerosis

Jerome Sullivan first proposed 30 years ago that iron deficiency may be protective against the development of ischemic heart disease [ [1] Sullivan J.L. Iron and the sex difference in heart disease risk. Lancet. 1981; 1: 1293-1294 Abstract PubMed Scopus (646) Google Scholar ]. Enthusiasm for this hypothesis was dampened by a series of studies which failed to show that conventional measurements of total body iron status were associated with increased atherosclerosis in man. However, one potential reason for the failure to demonstrate an association between iron and atherosclerosis in these studies may have been due to a failure to focus on the molecular form of iron which is most likely responsible for inducing atherosclerosis. Iron is a reasonable candidate for carrying out the oxidative modifications which are believed to be paramount in the atherosclerotic process [ [2] Sullivan J.L. Iron in arterial plaque: a modifiable risk factor for atherosclerosis. Biochem Biophys Acta. 2009; 1790: 718-723 Crossref PubMed Scopus (136) Google Scholar ]. Iron is capable of generating highly reactive label oxygen free radicals such as superoxide radical and hydroxyl radical under physiological conditions. However, most of the iron in our bodies is stored bound to professional iron binding proteins – transferrin or ferritin – in which the iron is redox inactive and not capable of inducing oxidation of substrates. Over the past 10 years it has become appreciated that there exists a small but tightly regulated pool of iron which is not bound to transferrin or ferritin and which is redox active (referred to as labile plasma non-transferrin bound iron or NTBI) [ 3 Breuer W. Hersko C. Cabantchik Z.I. The importance of non transferring bound iron in disorders of iron and metabolism. Transfus Sci. 2000; 23: 185-192 Abstract Full Text Full Text PDF PubMed Scopus (215) Google Scholar , 4 Breuer W. Shvartsman M. Cabantchik Z.I. Intracellular labile iron. Int J Biochem Cell Biol. 2008; 40: 350-354 Crossref PubMed Scopus (141) Google Scholar ]. NTBI represents a number of molecular species very few of which have been identified. One type of NTBI which has been identified is the iron contained within the haptoglobin–hemoglobin complex [ [5] Asleh R. Guetta J. Kalet-Litman S. Miller-Lotan R. Levy A.P. Haptoglobin genotype and diabetes dependent differences in iron mediated oxidative stress in vitro and in vivo. Circ Res. 2005; 96: 435-441 Crossref PubMed Scopus (175) Google Scholar ].

A high-performance liquid immunoaffinity chromatography method for determining transferrin-bound iron in serum

BackgroundThe analyzed values in the ICSH reference method for serum iron analysis are affected by non-transferrin(Tf)-bound iron such as ferritin. Also, non-Tf-bound plasma iron (iron citrate) is present in iron-overloaded specimens from patients with hemochromatosis, which was measured as serum iron in previous methods. We developed a specific determination method for serum transferrin-bound iron (serum t Fe) by high-performance liquid immunoaffinity chromatography (HPLAC), and compared it with the ICSH method and a fully automated (FA) method. MethodsTf and t Fe were isolated from interferents in serum by HPLC using an immunoaffinity column. The concentration of t Fe isolated was determined by a colorimetric reaction using a highly sensitive chromogen. ResultsInterferents, except iron saccharate (detected at 5%), do not affect t Fe determination. Within-run and between-run imprecisions were in the ranges of 0.2–0.4% and 0.4–1.0% CV. The results of the HPLAC method correlated well with those of the ICSH method (r=0.9993) and FA method (r=0.9984). ConclusionsIn contrast to the ICSH and FA methods for determining serum iron, the HPLAC method is simple, highly precise and specific for serum t Fe, which can contribute to the measurement of iron status.

Iron status and cardiovascular disease risk in black South African women: the PURE study

Objective: To examine the associations between measures of iron status and cardiovascular disease (CVD) risk factors in South African women.Method: In a cross-sectional study, demographic information and health history were obtained during individual interviews using validated questionnaires in the North West Province, South Africa. Anthropometric indices, iron indices, blood pressure, blood glucose and lipid profiles were measured using standard procedures in 1 262 apparently healthy black South African women aged 35 years or older. Iron status was assessed using serum concentrations of ferritin, transferrin receptor (TfR) and TfR:ferritin ratio.Results: Associations between iron status parameters and CVD risk factors were generally weak (r < 0.3, p < 0.01) and were not retained when adjustment was made for age, body mass index, smoking, alcohol consumption and C-reactive protein in the analysis. Waist circumference (WC) and waist:hip ratio (WHR) were higher in the fourth quartile of serum ferritin than in the third quartile, and also in the third quartile compared to the second quartile (P < 0.05). Based on WC and WHR respectively, 31% and 52% of the women had excess abdominal obesity. The mean (95% confidence interval) serum TfR concentration was high, at 9.09 µg/ml (8.77, 9.44), indicating risk of iron deficiency. The mean (95% confidence interval) concentrations of lipids [total cholesterol 4.78 mmol/l (4.64, 4.93), high-density lipoprotein cholesterol 1.45 mmol/l (1.39, 1.52), low-density lipoprotein cholesterol 1.65 mmol/l (1.53, 1.78), triglyceride 1.12 mmol/l (1.07, 1.18)] were within reference ranges.Conclusion: No significant association was found between iron status parameters and established CVD risk factors. However, excessive abdominal adiposity indicated by high WC and WHR contributes significantly to increased serum ferritin concentration in this population.

Analytical and Biological Variation in Measures of Anemia and Iron Status in Patients Treated With Maintenance Hemodialysis

To make informed decisions in dosing erythropoiesis-stimulating agents and intravenous iron therapy, clinicians must determine whether differences between current and previous test results for anemia and iron status markers reflect expected variation, a significant change, or an actual trend. Prospective observational cohort study. 30 patients undergoing thrice-weekly in-center hemodialysis. Within-patient biological variations in hemoglobin (Hb) level, hematocrit (Hct), reticulocyte Hb content, transferrin saturation (TSAT), and ferritin level were determined over 12 consecutive treatment days. We separately measured same-sample analytical variation and within-patient biological variation (coefficient of variation), then calculated the number of sampling days needed to determine the true or homeostatic value for each analyte with 95% probability. We also evaluated whether results differed among the first, second, and third dialysis days of the week. Biological variation differed by analyte. Hb level (4.0%), Hct (4.0%), and reticulocyte Hb content (4.8%) showed much lower variation than TSAT (38.2%) or ferritin level (15.1%). Analytical variation ranged from 2.0%-6.9% for all analytes. We found that one sample day would be sufficient to establish the true mean Hb level or Hct within a level of closeness+/-20% and 95% probability. For the same levels of closeness and probability, one sample day would be needed for reticulocyte Hb content, 15 for TSAT, and 3 for ferritin level. No pairwise comparison for any of the 5 analytes yielded a significant difference between results obtained on the first, second, or third dialysis day of the week. These findings may not apply to other patient populations. Low biological variation renders Hb level, Hct, and reticulocyte Hb content, but not TSAT and ferritin level, suitable for trend analysis using results from 2 successive samples. TSAT and ferritin test results, unlike reticulocyte Hb content, have limited value in evaluating changes in iron status within individual hemodialysis patients.

Complete blood count, measures of iron status and inflammatory markers in inner-city African Americans with undiagnosed hepatitis C seropositivity

Background Hepatitis C virus (HCV) infection may be associated with thrombocytopenia and increased iron stores in patients receiving medical care. We aimed to determine how often changes in hematologic, iron metabolic and inflammatory markers occur in individuals with undiagnosed HCV in the community. Methods Inner-city African Americans ( n = 143) were recruited from the community according to reported ingestion of alcohol. They were divided broadly into those who drank more or less than 56 g alcohol/day as assessed by dietary questionnaire. HCV serology was determined and laboratory values were compared according to HCV seropositivity in analyses that adjusted for alcohol consumption. Results The prevalence of HCV seropositivity was 23% among men and 29% among women. Levels of hepatocellular enzymes were higher with HCV seropositivity ( P < 0.0001) but hemoglobin concentrations, white blood cell and platelet counts and serum ferritin concentrations did not differ. The globulin fraction of the serum protein concentration ( P = 0.002) was increased with HCV seropositivity as expected with chronic inflammation. However, erythrocyte sedimentation rate and serum iron and haptoglobin levels did not differ significantly according to HCV status. Furthermore, multivariate analysis revealed that C-reactive protein was decreased and transferrin concentration was increased with both HCV and alcohol consumption ( P < 0.014). Conclusions Previously undiagnosed HCV seropositivity has little effect on the complete blood count and body iron stores but appears to perturb the response to an inflammatory stimulus, causing reduced rather than increased circulating CRP concentrations and increased rather than decreased transferrin concentrations.

The transplant iron score as a predictor of stem cell transplant survival

Recent studies have suggested that the presence of iron overload prior to stem cell transplantation is associated with decreased survival. Within these studies, the criteria used to define iron overload have varied considerably. Given the lack of consensus regarding the definition of iron overload in the transplant setting, we sought to methodically examine iron status among transplant patients. We studied 78 consecutive patients at risk for transfusion-related iron overload (diagnoses included AML, ALL, MDS, and aplastic anemia) who received either autologous or allogeneic stem cell transplant. Multiple measures of iron status were collected prior to transplantation and examined for their association with survival. Using this data, three potentially prognostic iron measures were identified and incorporated into a rational and unified scoring system. The resulting Transplant Iron Score assigns a point for each of the following variables: (1) greater than 25 red cell units transfused prior to transplantation; (2) serum ferritin > 1000 ng/ml; and (3) a semi-quantitative bone marrow iron stain of 6+. In our cohort, the score (range 0 to 3) was more closely associated with survival than any available single iron parameter. In multivariate analysis, we observed an independent effect of iron overload on transplant survival (p = 0.01) primarily attributable to an increase in early treatment-related deaths (p = 0.02) and lethal infections. In subgroup analysis, the predictive power of the iron score was most pronounced among allogeneic transplant patients, where a high score (≥ 2) was associated with a 50% absolute decrease in survival at one year. In summary, our results lend further credence to the notion that iron overload prior to transplant is detrimental and suggest iron overload may predispose to a higher rate of lethal infections.

Maternal pro-hepcidin at term correlates with cord blood pro-hepcidin at birth

Objective Hepcidin, a small 25 amino-acid antimicrobial peptide, has a significant role in the regulation of iron homeostasis. Pro-hepcidin, an 84 amino-acid peptide, is a precursor of the active hepcidin. The main aim of this study was to examine the association of maternal serum pro-hepcidin with cord blood pro-hepcidin levels in term pregnancies, and whether maternal and newborn iron status measurements correlate with the pro-hepcidin level. Study design The population consisted of 193 pregnant women admitted to the Kuopio University Hospital (Finland) for delivery, and their full-term newborn infants (cord blood). The main outcome measures were serum pro-hepcidin (ELISA), blood count including red cell indices, serum iron status markers (including iron, transferrin, transferrin saturation (TfSat), transferrin receptor (TfR) and ferritin), birth weight and placental weight and relative placental size. A Mann–Whitney U-test and Spearman's correlation were used to test the associations between the parameters. Results Pregnant women had higher pro-hepcidin level than their newborns (325 μg/L vs. 235 μg/L, p < 0.001). The Spearman's correlation between the maternal and cord blood serum pro-hepcidin level was highly significant (correlation coefficient 0.600, p < 0.001). Additionally, both maternal and cord blood pro-hepcidin levels correlated weakly but significantly with placental weight and relative placental size. However, pro-hepcidin level did not correlate with iron status measurements in pregnant women or in their newborns. Conclusions The present results suggest that pro-hepcidin is not associated with maternal or newborn iron homeostasis at term and birth, but may act in concert with the placenta, as evidenced by the correlation between maternal and fetal pro-hepcidin levels and their slight correlation with placental weight.

Assessment of iron deficiency in US preschool children and nonpregnant females of childbearing age: National Health and Nutrition Examination Survey 2003–2006

BackgroundA new index to determine body iron promises a simpler approach to monitoring iron deficiency (ID) prevalence. Objective:Our objective was to compare ID defined as body iron <0 mg/kg and calculated from the log ratio of transferrin receptor to ferritin (the body iron model) to ID defined as ≥2 of 3 abnormal concentrations in ferritin, transferrin saturation, or erythrocyte protoporphyrin (the ferritin model). Design:We used measures of iron status and inflammation from 486 children aged 1–2 y, 848 children aged 3–5 y, and 3742 nonpregnant females aged 12–49 y from the National Health and Nutrition Examination Survey 2003–2006. Results:ID prevalences (±SE) based on the body iron model in children (1–2 and 3–5 y) and in females (12–19 and 20–49 y) were 14.4 ± 1.9%, 3.7 ± 0.8%, 9.3 ± 1.0%, and 9.2 ± 1.6%, respectively. ID prevalences based on the ferritin model in children (3–5 y) and females (12–19 and 20–49 y) were 4.5 ± 0.9%, 15.6 ± 1.2%, and 15.7 ± 0.8%, respectively. The κ statistics for agreement between the 2 models were 0.5–0.7. Among females (12–49 y) the positive predictive values of ID based on the body iron model and the ferritin model for identifying anemia were 43 ± 3% and 30 ± 2%, respectively, whereas negative predictive values did not differ. C-reactive protein was elevated in 28.8 ± 3.1% of females with ID by the ferritin model but not by the body iron model and in 0% of persons with ID by the body iron model but not by the ferritin model. Conclusions:The agreement between the 2 indexes was fair to good. Among females, the body iron model produced lower estimates of ID prevalence, better predicted anemia, and appeared to be less affected by inflammation than the ferritin model.

Methods to assess iron status in various NHANES surveys.

This paper summarizes iron status measurements included in the three cross-sectional National Health and Nutrition Examination Surveys (NHANES) completed to date, as well as a special study of Hispanics, known as the Hispanic Health and Nutrition Examination Survey (HHANES). Approaches for defining iron status in the population based on these measurements are also described as well as issues in comparing iron status data between surveys, using NHANES II and III data as an example.

Neuronal functionality assessed by magnetoencephalography is related to oxidative stress system in acute ischemic stroke

The hypoxic brain damage induced by stroke is followed by an ischemia–reperfusion injury modulated by oxidative stress. Magnetoencephalographic (MEG) recording of rest and evoked cortical activities is a sensitive method to analyse functional changes following the acute ischemic damage. We aimed at investigating whether MEG signals are related to oxidative stress compounds in acute stroke. Eighteen stroke patients and 20 controls were enrolled. All subjects underwent MEG assessment to record background activity and somatosensory evoked responses (M20 and M30) of rolandic regions, neurological examination assessed by National Institute of Health Stroke Scale (NIHSS) and plasmatic measurement of copper, iron, zinc, ceruloplasmin, transferrin, total peroxides and Total Anti-Oxidant Status. Magnetic Resonance was performed to estimate the lesion site and volume. Delta power and M20 equivalent current dipole (ECD) strength in the affected hemisphere (AH) correlated with NIHSS scores (respectively, rho = .692, p = .006 and rho = − .627, p = .012) and taken together explained 67% of NIHSS variability ( p = .004). Higher transferrin and lower peroxides levels correlated with better clinical status (respectively, rho = − .600, p = .014 and rho = .599, p = .011). Transferrin also correlated with AH M20 ECD strength (rho = .638 p = .014) and inversely with AH delta power (rho = − .646 p = .023) and the lesion volume, especially in cortico-subcortical stroke ( p = .037). Our findings strengthen MEG reliability in honing the evaluation of neuronal damage in acute ischemic stroke also demonstrating an association between the MEG parameters most representing the clinical status and the oxidative stress compounds. Our results meet at a possible protective role of transferrin in limiting the oxidative damage in acute stroke.

Altered Iron Metabolism in Lymphocytes from Subjects with Restless Legs Syndrome

Studies using cerebrospinal fluid, magnetic resonance imaging, and autopsy tissue have implicated a primary role for brain iron insufficiency in restless legs syndrome (RLS). If the abnormalities of brain iron regulation reflect a basic disturbance of iron metabolism, then this might be expressed at least partially in some peripheral systems. Thus the study aim was to determine whether patients with RLS and control subjects show differences in lymphocyte iron regulator proteins. Fasting morning blood samples were used to obtain common serum measures of iron status and to determine lymphocyte iron management proteins. Twenty-four women with early-onset RLS and 25 control women without RLS symptoms were studied. RLS and control subjects were matched for age, hemoglobin, and serum iron profile. However, transferrin receptor (TfR) and DMT1 (divalent metal transporter 1 protein) levels in lymphocytes were significantly higher for RLS patients than for controls. No significant differences in ferritin subtypes or transferrin levels were found. No significant correlations were found between lymphocyte and serum indices of iron status. RLS lymphocytes showed an increase in ferroportin, implying increased cellular iron excretion, in the face of increased iron need (increased TfR and DMT1). In the absence of changes in H-ferritin, the findings indicate a balance between input and output with no net iron change but probable overall increase in iron turnover. The lack of any significant correlation between serum and lymphocyte iron indices indicates that iron management proteins from lymphocytes are at a minimum an alternative and independent marker of cellular iron metabolism.

Risk of severe depressive mood decreases with improving hemoglobin levels, but only when daytime salivary cortisol concentration is low

Previous research indicates that stressor exposure increases risk of severe depressive mood in iron deficient Hispanic women (Rahn 2007). Iron status, severity of depressive mood (Beck depression inventory, BDI), and salivary cortisol concentration were assessed in 48 female Mexican factory workers from the state of Morelos. Iron status measures were hemoglobin, ferritin, protoporphyrin, MCV and transferrin saturation. Salivary cortisol was sampled as a biological marker of stress for 2 successive days. The area under the cortisol concentration curve (AUC) over 7 daytime hours was estimated. Fatigue was assessed with the Fatigue Severity Scale. Mean age was 29 years; mean hemoglobin was 131 g/L (SD=18) and ranged from 8.8 to 16.1 g/L. Anemia with iron depletion occurred in 25% of subjects, while severe depressive mood (BDI score≥29) was found in 31%. The outcome of the logistic regression analysis was risk of severe depressive mood (BDI ≥29) compared to the reference group (BDI&lt;29). Hemoglobin (continuous) and AUC (&lt;median, ≥median) were combined in an interaction term; additional covariates were fatigue, and household crowding and SES. Women with AUC&lt;median had a 6% decrease (p‐value of subgroup=0.04) in odds of severe depressive mood with every one g/L increase of hemoglobin (p‐value of interaction=0.08); no significant slope was found with AUC≥median.This research was supported by the NIH predoctoral nutrition training grant 3 T32 DK007158‐29, the Einaudi Center for International Studies and the N.S. Meinig Professorship, Cornell University.

A randomized, double-blind, placebo-controlled trial of intravenous iron sucrose in restless legs syndrome

Objective The aim of this study was to ascertain whether high-dose intravenous (IV) iron sucrose could improve symptoms and change brain iron concentrations in idiopathic RLS. Methods The study was a randomized, parallel-group double-blind study of 1000 mg iron sucrose given IV versus placebo. Primary measures of the clinical status were global rating scale (GRS) and periodic leg movements of sleep (PLMS). Primary measures of brain iron status were CSF ferritin and MRI-determined iron in the substantia nigra. Results At the time of the interim analysis there were 7 placebo and 11 iron-treated subjects. At 2-weeks post-treatment, iron treatment resulted in a small but significant increase in CSF ferritin and a decrease in RLS severity (GRS) but did not change PLMS or MRI iron index. None of the secondary outcomes changed with treatment. There was no single case of clear treatment benefit in any of the patients. This interim analysis revealed an effect size that was too small to allow for adequate power to find significant differences with the planed 36-subject enrollment for either the primary objective outcome of PLMS or any of the secondary outcomes. The study was stopped at this planned break-point given the lack of both adequate power and any indication for clinically significant benefit. Conclusions High-dose IV iron failed to demonstrate the robust changes reported in three prior open-label studies. Differences in iron formulation, dosing regiment, and peripheral iron status may explain some of the discrepancies between this and previous IV iron treatment studies.

Iron Metabolism in Children: Confounding Factors

Characterization of iron metabolism in infants and children may be confounded by the diverse effects of developmental, genetic, and acquired influences on iron metabolism and laboratory measurements of iron status, especially in areas with intense perennial transmission of Plasmodium falciparum malaria. In the Pemba iron and folic acid supplementation trial, the coadministration of folic acid with iron is a further confounding factor. Because the design of the Pemba iron and folic acid supplementation study did not include a group that received iron supplementation without folic acid, the observed increase in serious adverse events cannot be ascribed unequivocally to iron alone, to folic acid alone, or to the combination of the two. In interpreting the results from the Pemba iron and folic acid supplementation trial, additional analyses of existing data from the trial and from earlier studies in the area could help clarify the roles of iron and folic acid.

Iron Deficiency in Early Childhood in the United States: Risk Factors and Racial/Ethnic Disparities

Iron deficiency affects 2.4 million US children, and childhood iron-deficiency anemia is associated with behavioral and cognitive delays. Given the detrimental long-term effects and high prevalence of iron deficiency, its prevention in early childhood is an important public health issue. The study objectives were to (1) identify risk factors for iron deficiency in US children 1 to 3 years old, using data from the most recent waves of the National Health and Nutrition Examination Survey IV (1999-2002) and (2) examine risk factors for iron deficiency among Hispanic toddlers, the largest minority group of US children. Analyses of the National Health and Nutrition Examination Survey IV were performed for a nationally representative sample of US children 1 to 3 years old. Iron-status measures were transferrin saturation, free erythrocyte protoporphyrin, and serum ferritin. Bivariate and multivariable analyses were performed to identify factors associated with iron deficiency. Among 1641 toddlers, 42% were Hispanic, 28% were white, and 25% were black. The iron deficiency prevalence was 12% among Hispanics versus 6% in whites and 6% in blacks. Iron deficiency prevalence was 20% among those with overweight, 8% for those at risk for overweight, and 7% for normal-weight toddlers. Fourteen percent of toddlers with parents interviewed in a non-English language had iron deficiency versus 7% of toddlers with parents interviewed in English. Five percent of toddlers in day care and 10% of the toddlers not in day care had iron deficiency. Hispanic toddlers were significantly more likely than white and black toddlers to be overweight (16% vs 5% vs 4%) and not in day care (70% vs 50% vs 43%). In multivariable analyses, overweight toddlers and those not in day care had higher odds of iron deficiency. Toddlers who are overweight and not in day care are at high risk for iron deficiency. Hispanic toddlers are more likely than white and black toddlers to be overweight and not in day care. The higher prevalence of these risk factors among Hispanic toddlers may account for their increased prevalence of iron deficiency.