Association of body iron stores and anemia in a Ghanaian type-2 diabetes mellitus population: A multicentered cross-sectional study.

Background and Aims: Anemia has been a common comorbidity in most chronic diseases, but has not been well monitored in type 2 diabetes mellitus (T2DM) patients. In this study, we investigated the prevalence of anemia and its nexus with iron stores among T2DM patients in health facilities in the Ashanti Region of Ghana. Methods: This multicenter cross-sectional study recruited 213 T2DM out-patients attending the diabetic clinics at the Kumasi South Hospital and St. Michaels Hospital, Jachie Pramso, Ghana, for routine check-ups. Self-reported questionnaires were used to collect sociodemographic, lifestyle, and clinical data from study participants. Blood samples were collected to estimate hematological parameters and iron stores. Mann-Whitney U test was used to assess the difference in hematological parameters and iron stores between anemic and nonanemic patients. All p < 0.05 were considered statistically significant. Results: Of the 213 T2DM participants, the prevalence of anemia was 31.9%. More females 145 (68.1%) were registered than males 68 (31.9%). Anemic patients had significantly lower levels of mean cell volume [79.30/fL vs. 82.60/fL, p = 0.001], mean cell hemoglobin [26.60/pg vs. 27.90/pg, p < 0.0001], and mean cell hemoglobin concentration [33.10/g/dL) vs. 33.80/g/dL, p < 0.0001] than those without anemia. Serum levels of ferritin (p = 0.1140), transferrin (p = 0.5070), iron (p = 0.7950), and total iron binding capacity (p = 0.4610) did not differ significantly between T2DM patients with or without anemia. Conclusion: Despite the high prevalence of anemia among the T2DM patients in our cohort, patients present with apparently normal iron stores. This unrecognized mild anemia must be frequently monitored among T2DM patients.

Lower serum ferritin levels are associated with worse cognitive performance in aging.

OBJECTIVES: Iron is important for neurogenesis, synaptic development, and neurotransmitter synthesis. Serum ferritin (SF) is a reliable marker for assessing iron stores. Therefore, we evaluated the cognitive function associated with SF levels. We also assessed brain iron content using R2* Magnetic Resonance Imaging (MRI) and its association with SF levels. DESIGN: Data from three cross-sectional observational studies were used. Aging Imageomics (n = 1030) was conducted on aged subjects. Health Imageomics (n = 971) and IR0NMET (n = 175) were conducted in middle-aged subjects. SETTING AND PARTICIPANTS: Participants were enrolled at Dr. Josep Trueta University Hospital facilities. The three cohorts included a total of 2176 subjects (mean age, 52 years; 48% men). MEASUREMENTS: SF levels were measured by standard laboratory methods. Total Digits Span (TDS), and Phonemic Verbal Fluency (PVF) were used to assess executive function. Language function was assessed by semantic verbal fluency (SVF), attention by the Symbol Digit Modalities Test, and memory by the Memory Binding Tests - Total Free Recall and Total Delayed Free Recall. MRI was used to assess the iron content of the brain by R2*. RESULTS: In subjects aged 65 years or older, SF levels were associated with increased TDS (ß = 0.003, p = 0.02), PVF (ß = 0.004, p = 0.01), and SVF (ß = 0.004, p = 0.002) scores. After stratification by sex, these findings were significant only in men, where SF was associated with increased TDS (ß = 0.003, p = 0.01), PVF (ß = 0.004, p = 0.03), and SVF (ß = 0.004, p = 0.009) scores. In middle-aged subjects, SF was also associated with increased SVF scores (ß = 0.005, p = 0.011). Lastly, in men, SF levels were negatively associated with R2*, a surrogate marker of brain iron content, in both the left frontal inferior opercular area (r = -0.41, p = 0.005) and the right frontal inferior opercular area (r = -0.44, p = 0.002). CONCLUSIONS: SF is significantly and positively associated with cognition. In older people with low SF levels, iron supplementation may be a promising therapy to improve cognition.

An 8-Week Vitamin D3-Fortified Fruit Drink Supplementation Increases Serum Ferritin Concentration: A Randomized Controlled Trial in Malaysian Women With Low Iron Stores.

BACKGROUND: There is limited randomized controlled trial evidence to support the association between vitamin D deficiency and anemia risk, highlighting the necessity for further investigations into the role of vitamin D in influencing iron status. OBJECTIVE: The aim of this study was to determine the effect of vitamin D3-fortified fruit drink consumption (4,000 IU) on vitamin D and iron status biomarkers among iron-deficient women (serum ferritin of <20 µg/L [to convert µg/L ferritin to ng/mL, multiply by 1]). DESIGN: An 8-week double-blind randomized controlled trial was conducted. SUBJECTS/SETTING: A total of 45 healthy, nonpregnant, nonlactating subjects aged 18 through 40 years (mean [SD] 25.3 [4.6] years) were included in the study, excluding those who donated blood 6 months prior, regularly consumed nutritional supplements, or had gastrointestinal or iron metabolic disorders. INTERVENTION: Subjects were randomly assigned to receive either vitamin D3-fortified fruit drink or a placebo. MAIN OUTCOME MEASURES: Measurements of 25-hydroxyvitamin D (25[OH]D), serum ferritin, high-sensitivity C-reactive protein, and full blood count concentrations were obtained at baseline, interim, and post intervention. STATISTICAL ANALYSES: A mixed model, repeated measures analysis of variance was used to analyze the intervention effect. RESULTS: Attrition rate for the study was 13%, with 6 dropouts, and 39 subjects completed the study. Daily consumption of vitamin D3-fortified fruit drink in the intervention group resulted in significant increases in 25(OH)D and serum ferritin concentrations compared with the placebo group. The intervention group showed significantly higher mean (SD) changes (Δ) in both 25(OH)D (Δ 76.4 [30.2] nmol/L [to convert nmol/L 25(OH)D to ng/mL, multiply by .4] vs Δ -1.3 [10.7] nmol/L; P = .001) and serum ferritin concentrations (Δ 2.2 [4.2] µg/L vs Δ -0.3 [3.4] µg/L; P = .048) between baseline and post intervention. The other iron status biomarkers were not affected by the intervention. CONCLUSIONS: Our study found that daily vitamin D3-fortified fruit drink supplementation for 8 weeks effectively improved 25(OH)D and iron stores, indicated by increased serum ferritin concentrations, in iron-deficient women. Further research is needed to evaluate its safety, efficacy, feasibility, and optimal food fortification in diverse populations.

Risk prediction of iron deficiency for plasmapheresis donors in China: Development and validation of a prediction model.

BACKGROUND AND OBJECTIVES: The present study aims to evaluate the iron stores in plasmapheresis donors and develop and validate an iron deficiency (ID) risk prediction model for plasmapheresis donors with potential or existing ID. MATERIALS AND METHODS: We assessed plasmapheresis donors' serum ferritin (SF) and haemoglobin (Hb) levels. The candidate factors showing significant differences in the multivariate logistic regression analysis were used to establish a risk prediction scoring system. The participants were divided into a training cohort and an internal validation cohort in a 7:3 ratio. Additional plasmapheresis donors from a different station were recruited for external validation. RESULTS: The SF levels in both male and female donors in the high-frequency group were significantly lower than those of new donors (male: p < 0.001; female: p = 0.008). The prevalence of ID in female regular donors with a high frequency was significantly higher than that in new donors (33.1% vs. 24.6%; odds ratio = 1.209 [95% CI: 1.035-1.412]). Donation frequency, age, Hb, body mass index and being pre-menopausal were identified as independent risk factors for ID (p < 0.05). The developed model exhibited good discrimination ability (area under the receiver operating characteristic curve >0.7) and calibration (p > 0.05) in development, internal validation cohorts and external validation cohorts. CONCLUSION: A higher donation frequency has been associated with reduced SF levels and an increased risk of ID in women. The developed ID risk prediction model demonstrates moderate discriminative power and good model fitting, suggesting its potential clinical utility.

Gut microbiota links to serum ferritin and cognition.

Iron is required for the replication and growth of almost all bacterial species and in the production of myelin and neurotransmitters. Increasing clinical studies evidence that the gut microbiota plays a critical role in iron metabolism and cognition. However, the understanding of the complex iron-microbiome-cognition crosstalk remains elusive. In a recent study in the Aging Imageomics cohort (n = 1,030), we identified a positive association of serum ferritin (SF) with executive function (EF) as inferred from the semantic verbal fluency (SVF,) the total digit span (TDS) and the phonemic verbal fluency tests (PVF). Here, we explored the potential mechanisms by analyzing the gut microbiome and plasma metabolome using shotgun metagenomics and HPLC-ESI-MS/MS, respectively. Different bacterial species belonging to the Proteobacteria phylum (Klebsiella pneumoniae, Klebsiella michiganensis, Unclassified Escherichia) were negatively associated both with SF and executive function. At the functional level, an enrichment of microbial pathways involved in phenylalanine, arginine, and proline metabolism was identified. Consistently, phenylacetylglutamine, a metabolite derived from microbial catabolism of phenylalanine, was negatively associated with SF, EF, and semantic memory. Other metabolites such as ureidobutyric acid and 19,20-DiHDPA, a DHA-derived oxylipin, were also consistently and negatively associated with SF, EF, and semantic memory, while plasma eicosapentaenoic acid was positively associated. The associations of SF with cognition could be mediated by the gut microbiome through microbial-derived metabolites.

Alcoholic Hepatitis Mimicking Iron Overload Disorders With Hyperferritinemia and Severely Elevated Transferrin Saturation: A Case Report.

Iron overload disorders can present as non-specific symptoms and develop gradually but, if untreated, can be very fatal. The common causes include multiple blood transfusions for chronic anemia and increased iron absorption, including hereditary hemochromatosis (HH). HH is one of the common causes of iron overload disorders and usually presents with liver cirrhosis in a setting of significantly elevated ferritin and elevated transferrin saturation. Alcoholic hepatitis is a clinical syndrome of progressive inflammatory liver injury associated with long-term heavy intake of ethanol. However, in patients with alcohol abuse, excessive alcohol consumption can disrupt iron metabolism releasing large amounts of iron into circulation. This can cause severely elevated ferritin due to disruption of iron metabolism, simulating iron overload disorders such as HH, especially if the patient also has liver cirrhosis. Even though a high transferrin saturation of greater than 45% is recommended as a cutoff transferrin value as high sensitivity for detecting iron overload disorders, it has a low specificity and positive predictive value and often identifies people with other causes of acutely elevated ferritin levels such as alcohol liver disease and hepatitis. Recognizing this feature and timely management can spare the patient from unnecessary phlebotomies and prompt treatment for alcoholic hepatitis. We present an interesting case of severe alcoholic hepatitis mimicking HH with severely elevated ferritin levels and transferrin saturation with underlying liver cirrhosis.

Serum ferritin and the risk of short-term mortality in critically ill patients with chronic heart failure: a retrospective cohort study.

Background: Serum ferritin levels are associated with a higher risk of incident heart failure (HF). Whether serum ferritin levels, either increased or decreased, predict the risk of mortality in individuals with chronic heart failure (CHF) remains unknown. Objectives: This study aimed to clarify the potential predictive significance of serum ferritin levels in assessing the short-term mortality in critically ill patients with chronic heart failure (CHF). Methods: Critically ill patients with CHF were identified from the Multiparameter Intelligent Monitoring in Intensive Care III and IV (MIMIC III and IV) databases. Linear and logistic regression models and Cox proportional hazards models were applied to assess the associations between serum ferritin and survival. Results: A total of 1,739 and 2,322 patients with CHF identified from the MIMIC III and IV databases, respectively, fulfilled the inclusion criteria. In the MIMIC III group, compared with the reference group (serum ferritin ≥70 and <500 ng/mL), serum ferritin ≥1000 ng/mL was a significant predictor of 28-day (odds ratio [OR], 1.76; 95% confidence interval [CI], 1.14-2.72) and 90-day mortality (OR, 1.64; 95% CI, 1.13-2.39). The results from the Cox regression and Kaplan-Meier curves revealed similar results. In the MIMIC IV group, serum ferritin ≥1000 ng/mL was a significant predictor of in-hospital (OR, 1.70; 95% CI, 1.18-2.46), 28-day (OR, 1.83; 95% CI, 1.24-2.69), and 90-day mortality (OR, 1.57; 95% CI, 1.11-2.22) after adjusting for confounding factors. Conclusion: High ferritin levels (≥1000 ng/mL) were associated with increased short-term mortality in critically ill patients with CHF, indicating that serum ferritin may serve as a useful prognostic marker for CHF.

Body Iron Store and its Association with Risk of First Episode of Spontaneous Lower Extremity Deep Vein Thrombosis/ Pulmonary Embolism: A Case-Control Study.

Background and objectives: The association between body iron stores and risk of deep vein thrombosis/ pulmonary embolism (DVT/ PE) has not been studied among Indian subjects. This study aimed to evaluate the same and also study the association between iron stores and recanalization of affected veins at week-12. Methods: This Case-Control with follow-up study enrolled 85 consecutive adult (≥ 18 years) cases presenting with first episode of spontaneous, proximal lower extremity DVT/ PE and 170 age (± 3 years) and sex matched adult controls without DVT/ PE. Those with haemoglobin(Hb) < 9 g/dl, malignancies, serum creatinine ≥ 2 mg/dL, heart failure and concurrent infections/ inflammatory disorders were excluded. All participants underwent iron profile, serum ferritin light-chain (FtL) and hepcidin testing. Results: Anaemia [OR = 2.3 (95% CI = 1.3-4.0), p = 0.001] and elevated RDW (RDW-CV > 15%) [OR = 2.3 (95% CI = 1.2-4.3), p = 0.012] were significantly associated with increased risk of DVT/ PE. Iron deficiency (ID, defined as serum ferritin < 30 µg/L, along with TSAT < 20%) was not associated with DVT/ PE risk [OR = 0.8 (95% CI = 0.4-1.7), p > 0.05]. Serum FtL in the highest quartile (> 75th centile) was associated with higher risk of DVT/ PE (OR = 5, 95% CI = 2.6-9.6) and levels < 25th centile with protection against DVT/ PE (OR = 0.1, 95% CI = 0.01-0.32), compared to levels between 25th and 75th centiles (referent range). Highest DVT/ PE risk was associated with FtL > 90th centile [OR≈12 (95% CI = 3.9-37.2)]. No associations were noted between serum hepcidin and DVT/ PE risk and ID and DVT recanalization at week-12. Conclusion: Higher iron stores, rather than ID, were associated with increased risk of DVT/ PE among those with Hb ≥ 9 g/dL. Anaemia and elevated RDW were also associated with risk of DVT/ PE. ID was not associated with poorer DVT recanalization at week-12.

Association Between Ferritin Levels and Altitude-Dependent Cardiorespiratory Fitness in Mountain Guides.

Pühringer, Reinhard, Martina Muckenthaler, and Martin Burtscher. Association between ferritin levels and altitude-dependent cardiorespiratory fitness in mountain guides. High Alt Med Biol. 24:139-143, 2023. Background: Higher ferritin levels may be associated with lower cardiorespiratory fitness (CRF; i.e., maximal oxygen uptake, VO2max) and may represent early markers of cardiovascular risk but may also support high-altitude acclimatization. To evaluate these potential associations, data recordings from a large sample of male mountain guides have been analyzed. Methods: A total of 154 data sets (including anthropometric data, VO2max, blood lipids, hemoglobin, ferritin, and transferrin levels) of regularly physically active and well-acclimatized mountain guides were available for analyses. Participants performed equal incremental cycle ergometer tests to exhaustion at low (600 m) and (∼1 week later) at moderate altitude (2,000 m). Results: Ferritin levels were positively correlated with levels of hemoglobin (r = 0.29, p < 0.01), total cholesterol (r = 0.18, p < 0.05), triglycerides (r = 0.23, p < 0.01), and low-density lipoprotein (r = 0.22, p < 0.01), and negatively with high-density lipoprotein levels (r = -0.16, p < 0.05) and also with baseline (taken at low altitude) VO2max values (r = -0.19, p < 0.05). In contrast, higher ferritin levels were associated with less VO2max decline from low-to-moderate altitude (r = 0.26, p < 0.01). Conclusion: Higher ferritin levels in male mountain guides are weakly associated with lower CRF and higher prevalence of cardiovascular risk factors but with slightly less reduction in VO2max when acutely exposed to moderate altitude. The clinical relevance of these observations needs further investigation.

Iron Status and Associated Factors among Canadian Women: Results from the Canadian Health Measures Survey.

BACKGROUND: Iron deficiency and overload may negatively impact women's health. There has been limited assessment of iron status and its associated factors among Canadian women. OBJECTIVES: This study investigated associations of various sociodemographic, lifestyle, medication, and dietary factors with body iron stores among pre- and postmenopausal women in Canada. METHODS: Analyses were conducted using cross-sectional, nationally representative survey and biomarker data from women aged 20-79 y (n = 6362) in the Canadian Health Measures Survey (2009-2017). Body iron stores were assessed by measuring serum concentrations of ferritin (SF). Information on potential correlates was collected during an in-home interview. Multivariable linear regression analyses were performed to evaluate associations with SF concentration, and logistic regression was used to estimate associations with iron deficiency (SF <15 µg/L) or elevated iron stores (SF >150 µg/L). RESULTS: Geometric mean SF concentrations were significantly higher in postmenopausal than in premenopausal women (73.2 versus 33.8 µg/L; P < 0.001). The prevalence of iron deficiency among pre- and postmenopausal women was 16.0% and 4.0%, respectively, whereas that of elevated iron stores was 2.7% and 21.0%, respectively. After simultaneous adjustment for multiple factors, including high-sensitivity CRP (inflammation marker), we found that age, East/Southeast Asian (versus White) race/ethnicity, alcohol, and red meat consumption were positively associated with SF concentration among pre- and postmenopausal women. In addition, aspirin use and dairy consumption were inversely associated with SF concentration among postmenopausal women only. Similar patterns were observed for associations with elevated iron stores among postmenopausal women, whereas higher grain consumption was associated with an increased prevalence of iron deficiency among premenopausal women. CONCLUSIONS: Sociodemographic, lifestyle, medication, and dietary factors are correlated with iron status determined by SF concentration among Canadian women. The findings may have implications for intervention strategies aimed at optimizing body iron stores in pre- and postmenopausal women.

Iron stores in steady-state sickle cell disease children accessing care at a sickle cell disease clinic in Kumasi, Ghana: A cross-sectional study.

Background and Aims: Children with sickle cell disease (SCD) have an increased risk of multiple hemotransfusions and this can predispose them to elevated iron stores. The objectives of the study were to determine the extent of elevated iron stores and the associated risk factors in a population of steady-state SCD children in Ghana. Methods: This cross-sectional study was conducted at the pediatric sickle cell clinic at the Komfo Anokye Teaching Hospital. Complete blood count and serum ferritin assay were performed for (n = 178) steady-state SCD children. Descriptive and multivariate logistic regression analysis were performed. Elevated iron stores were defined as serum ferritin levels >300 ng/ml. Statistical significance was considered at p < 0.05. Results: The mean (standard deviation) age of the participants was 9.61 (±4.34) years, and 51% of them were males. About 17% of SCD children had elevated iron stores and receiving at least three hemotransfusions during the last 12 months was strongly associated with elevated iron stores (p < 0.001). History of chronic hemotransfusion increased the odds of having elevated iron store (adjusted odds ratio [aOR] = 11.41; 95% confidence interval [CI] = 3.11-30.85; p < 0.001) but SCD patients on hydroxyurea treatment had reduced-odds of having elevated iron stores (aOR = 0.18; 95% CI = 0.06-0.602; p = 0.006). Moreover, red blood cell (Coef. = -0.84; 95% CI = -0.37, -1.32; p = 0.001), hemoglobin (Coef. = -0.83; 95% CI = -0.05, -1.61; p = 0.04), hematocrit (Coef. = -0.85; 95% CI = -0.08, -1.63; p = 0.03), mean cell volume (Coef. = 0.02; 95% CI = 0.01, 0.03; p = 0.001) and mean cell hemoglobin (Coef. = 0.04; 95% CI = 0.01, 0.07; p = 0.002) could significantly predict serum ferritin levels. Conclusion: The magnitude of elevated iron stores was high among children with SCD in steady-state. Red cell indices could provide invaluable information regarding the risk of elevated iron stores. SCD children who have a history of chronic hemotransfusion or had received at least three hemotransfusions in a year should be monitored for elevated iron stores.

Assessment of serum iron stores in regular plateletpheresis donors.

BACKGROUND: Iron deficiency anaemia is the most common nutritional deficiency disorder in the world. Iron deficiency is a potential complication in repeated apheresis donation. The present study was aimed to evaluate serum iron stores in regular plateletpheresis donors. MATERIALS AND METHODS: A total of 60 donors were included in this study, which included 30 regular plateletpheresis donors as cases and controls were 30 first time donors. The donor samples were collected before donation for complete hemogram, transfusion transmissible infections screening and serum iron, total iron binding capacity, percentage saturation of transferrin and serum ferritin. RESULTS: Out of 60 donors, more than half of the donors (56.6 %) had serum ferritin less than 30 ng/mL. Out of these 34 donors, 25 were from the case group and 9 donors in the control group. The median serum ferritin level in cases and controls was 11.86 ng/mL (Interquartile range 4.18-17.34 ng/mL) and 37.92 ng/mL (Interquartile range 27.87-86.20 ng/mL) respectively (p < 0.001). The mean serum iron in cases and controls was 71.23 ± 31.32 µg/dL and 93.53 ± 33.53 µg/dL respectively (p = 0.016). The mean percentage saturation in cases and controls was 20.09 ± 9.31 % and 26.26 ± 9.03 % respectively (p = 0.012). A significant decline in mean serum ferritin with increase in number of annual donations and decrease in donation interval was observed. DISCUSSION: Regular plateletpheresis donation may lead to depletion of iron stores and subclinical iron deficiency. Donors with high platelet count are more likely to exhibit iron deficiency. Periodic serum ferritin estimation in donors participating in regular plateletpheresis donation is warranted.

Effects of repeated blood donation on iron status of blood donors in Zimbabwe: A cross-sectional study.

INTRODUCTION: Iron deficiency is a major complication of repeated blood donation. However, most of the blood screening methods employed by blood collection agents do not include iron status markers, leading to possible subclinical iron deficiency. The aim of this study was to evaluate the effects of repeated blood donation on the iron status of this vulnerable population in Zimbabwe. METHODS: All donors were categorized into groups based on number of donations made in the previous 2-year period prior to enrolment into the study. Serum iron, total iron-binding capacity (TIBC), and ferritin were analyzed on automated chemistry analyzers while transferrin saturation (TSAT) was calculated. The Wilcoxon rank-sum and ANOVA tests were used to assess the variation of iron profiles by gender and frequency of donations. All data analysis was performed using Stata software v13. RESULTS: Study participants included 170 repeat donors and 20 first-time blood donors. The median (IQR) age was 23 (19-27) years, while the majority were males 57% (n = 109/190). The overall prevalence of iron deficiency and reduced iron stores was 12.6% and 38.9%, respectively. There were statistically significant differences between males and females in all the iron status parameters (P < .05). TIBC increased with number of donations, while iron, ferritin, and TSAT decreased with increased number of donations. CONCLUSION: A high proportion of blood donors had iron deficiency despite being eligible to donate. Repeated blood donation may lead to substantial reduction in iron stores among blood donors. Inclusion of iron biochemical markers may enhance proper screening and monitoring of blood donors in Zimbabwe to prevent development of iron deficiency anemia.

The relationship between markers of antenatal iron stores and birth outcomes differs by malaria prevention regimen-a prospective cohort study.

BACKGROUND: Iron deficiency (ID) has been associated with adverse pregnancy outcomes, maternal anaemia, and altered susceptibility to infection. In Papua New Guinea (PNG), monthly treatment with sulphadoxine-pyrimethamine plus azithromycin (SPAZ) prevented low birthweight (LBW; <2500 g) through a combination of anti-malarial and non-malarial effects when compared to a single treatment with SP plus chloroquine (SPCQ) at first antenatal visit. We assessed the relationship between ID and adverse birth outcomes in women receiving SPAZ or SPCQ, and the mediating effects of malaria infection and haemoglobin levels during pregnancy. METHODS: Plasma ferritin levels measured at antenatal enrolment in a cohort of 1892 women were adjusted for concomitant inflammation using C-reactive protein and α-1-acid glycoprotein. Associations of ID (defined as ferritin <15 µg/L) or ferritin levels with birth outcomes (birthweight, LBW, preterm birth, small-for-gestational-age birthweight [SGA]) were determined using linear or logistic regression analysis, as appropriate. Mediation analysis assessed the degree of mediation of ID-birth outcome relationships by malaria infection or haemoglobin levels. RESULTS: At first antenatal visit (median gestational age, 22 weeks), 1256 women (66.4%) had ID. Overall, ID or ferritin levels at first antenatal visit were not associated with birth outcomes. There was effect modification by treatment arm. Amongst SPCQ recipients, ID was associated with a 81-g higher mean birthweight (95% confidence interval [CI] 10, 152; P = 0.025), and a twofold increase in ferritin levels was associated with increased odds of SGA (adjusted odds ratio [aOR] 1.25; 95% CI 1.06, 1.46; P = 0.007). By contrast, amongst SPAZ recipients, a twofold increase in ferritin was associated with reduced odds of LBW (aOR 0.80; 95% CI 0.67, 0.94; P = 0.009). Mediation analyses suggested that malaria infection or haemoglobin levels during pregnancy do not substantially mediate the association of ID with birth outcomes amongst SPCQ recipients. CONCLUSIONS: Improved antenatal iron stores do not confer a benefit for the prevention of adverse birth outcomes in the context of malaria chemoprevention strategies that lack the non-malarial properties of monthly SPAZ. Research to determine the mechanisms by which ID protects from suboptimal foetal growth is needed to guide the design of new malaria prevention strategies and to inform iron supplementation policy in malaria-endemic settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT01136850 .

Cut-off points for serum ferritin to identify low iron stores during the first year of life in a cohort of Mexican infants.

The aim of this study was to identify serum ferritin (SF) cut-off points (COPs) in a cohort of healthy full-term normal birth weight infants who had repeated measurements of SF and haemoglobin every 3 months during the first year of life. The study included 746 full-term infants with birth weight ≥2,500 g, having uncomplicated gestations and births. Participants received prophylactic iron supplementation (1 mg/day of iron element) from the first to the 12th month of life and did not develop anaemia during the first year of life. Two statistical methods were considered to identify COPs for low iron stores at 3, 6, 9 and 12 months of age: deviation from mean and cluster analysis. According to the K-means cluster analysis results by age and sex, COPs at 3 and 6 months for girls were 39 and 21 µg/L and for boys 23 and 11 µg/L, respectively. A single COP of 10 µg/L was identified, for girls and boys, at both 9 and 12 months. Given the physiological changes in SF concentration during the first year of life, our study identified dynamic COPs, which differed by sex in the first semester. Adequate SF COPs are necessary to identify low iron stores at an early stage of iron deficiency, which represents one of the most widespread public health problems around the world, particularly in low- and middle-income countries.

Association between maternal plasma ferritin concentration, iron supplement use, and the risk of gestational diabetes: a prospective cohort study.

BACKGROUND: The association between iron supplementation and gestational diabetes mellitus (GDM) is still inconclusive, and this association has not been extensively studied in relation to plasma ferritin in the early second trimester. OBJECTIVES: We aimed to prospectively examine the independent and combined associations of plasma ferritin concentrations and iron supplement use with GDM. METHODS: We studied 2117 women from the Tongji Maternal and Child Health Cohort in Wuhan, China. Plasma ferritin around 16 weeks' gestation was measured by ELISA kits and information on iron supplement use was collected by questionnaires. GDM was diagnosed by a 75-g oral-glucose-tolerance test (OGTT) at 24-28 weeks' gestation. A log-Poisson regression model was used to estimate the RR of GDM associated with plasma ferritin and iron supplementation. RESULTS: The median and IQR of plasma ferritin was 52.1 (29.6-89.9) ng/mL, and 863 (40.8%) participants reported use of iron supplements during the second trimester. A total of 219 (10.3%) participants developed GDM. Adjusted RRs (95% CIs) for GDM across increasing quartiles of plasma ferritin were 1.00 (reference), 2.14 (1.37, 3.34), 2.03 (1.30, 3.19), and 2.72 (1.76, 4.21), respectively. After adjustment, supplemental iron ≥60 mg/d during the second trimester was associated with an increased risk of GDM compared with nonusers (RR: 1.37; 95% CI: 1.02, 1.84). CONCLUSIONS: Both elevated plasma ferritin concentrations in the early second trimester and use of ≥60 mg/d of supplemental iron during pregnancy are independently associated with increased risk of GDM. Further clinical trials with precision nutrition approaches considering both baseline iron status and supplement use are needed to evaluate the benefits and risks of iron supplementation during pregnancy.

Baseline Hemoglobin, Hepcidin, Ferritin, and Total Body Iron Stores are Equally Strong Diagnostic Predictors of a Hemoglobin Response to 12 Weeks of Daily Iron Supplementation in Cambodian Women.

BACKGROUND: The WHO recommends daily iron supplementation for all women in areas where the population-level anemia prevalence is ≥40%, despite the fact that hemoglobin (Hb) concentration is generally considered to be a poor prognostic indicator of iron status. OBJECTIVES: In this secondary analysis, we investigated the predictive power of ten baseline hematological biomarkers towards a 12-week Hb response to iron supplementation. METHODS: Data were obtained from a randomized controlled trial of daily iron supplementation in 407 nonpregnant Cambodian women (18-45 years) who received 60 mg elemental iron as ferrous sulfate for 12 weeks. Ten baseline biomarkers were included: Hb, measured with both a hematology analyzer and a HemoCue; inflammation-adjusted ferritin; soluble transferrin receptor; reticulocyte Hb; hepcidin; mean corpuscular volume; inflammation-adjusted total body iron stores (TBIS); total iron binding capacity; and transferrin saturation. Receiver operating characteristic (ROC) curves from fitted logistic regression models were used to make discrimination comparisons and variable selection methods were used to construct a multibiomarker prognostic model. RESULTS: Only 25% (n = 95/383) of women who completed the trial experienced a 12-week Hb response ≥10 g/L. The strongest univariate predictors of a Hb response were Hb as measured with a hematology analyzer, inflammation-adjusted ferritin, hepcidin, and inflammation-adjusted TBIS (AUCROC = 0.81, 0.83, 0.82, and 0.82, respectively), and the optimal cutoffs to identify women who were likely to experience a Hb response were 117 g/L, 17.3 µg/L, 1.98 nmol/L, and 1.95 mg/kg, respectively. Hb as measured with a hematology analyzer, inflammation-adjusted ferritin, and hepcidin had the best combined predictive ability (AUCROC=0.86). Hb measured with the HemoCue had poor discrimination ability (AUCROC = 0.65). CONCLUSIONS: Baseline Hb as measured with a hematology analyzer was as strong a predictor of Hb response to iron supplementation as inflammation-adjusted ferritin, hepcidin, and inflammation-adjusted TBIS. This is positive given that the WHO currently uses the population-level anemia prevalence to guide recommendations for untargeted iron supplementation.

Iron status in athletic females, a shift in perspective on an old paradigm.

Iron deficiency is a common nutrient deficiency within athletes, with sport scientists and medical professionals recognizing that athletes require regular monitoring of their iron status during intense training periods. Revised considerations for athlete iron screening and monitoring have suggested that males get screened biannually during heavy training periods and females require screening biannually or quarterly, depending on their previous history of iron deficiency. The prevalence of iron deficiency in female athletes is higher than their male counterparts and is often cited as being a result of the presence of a menstrual cycle in the premenopausal years. This review has sought to revise our current understanding of female physiology and the interaction between primary reproductive hormones (oestrogen and progesterone) and iron homoeostasis in females. The review highlights an apparent symbiotic relationship between iron metabolism and the menstrual cycle that requires additional research as well as identifying areas of the menstrual cycle that may be primed for nutritional iron supplementation.

Iron stores at birth in a full-term normal birth weight birth cohort with a low level of inflammation.

Iron stores at birth are essential to meet iron needs during the first 4-6 months of life. The present study aimed to investigate iron stores in normal birth weight, healthy, term neonates. Umbilical cord blood samples were collected from apparently normal singleton vaginal deliveries (n=854). Subjects were screened and excluded if C-reactive protein (CRP) > 5 mg/l or α1-acid glycoprotein (AGP) > 1 g/l, preterm (<37 complete weeks), term < 2500g or term > 4000g. In total, 762 samples were included in the study. Serum ferritin, soluble transferrin receptor (sTfR), hepcidin, and erythropoietin (EPO) were measured in umbilical cord blood samples; total body iron (TBI) (mg/kg) was calculated using sTfR and ferritin concentrations. A total of 19.8% newborns were iron deficient (ferritin 35 µg/l) and an additional 46.6% had insufficient iron stores (ferritin < 76 µg/l). There was a positive association between serum ferritin and sTfR, hepcidin, and EPO. Gestational age was positively associated with ferritin, sTfR, EPO, and hepcidin. In conclusion, we demonstrate a high prevalence of insufficient iron stores in a Chinese birth cohort. The value of cord sTfR and TBI in the assessment of iron status in the newborn is questionable, and reference ranges need to be established.

Marathon Run-induced Changes in the Erythropoietin-Erythroferrone-Hepcidin Axis are Iron Dependent.

Alterations in iron metabolism after physical activity are manifested through the rise of blood hepcidin (Hpc) levels. However, in many athletes, no changes in Hpc levels are observed after exercise despite the presence of inflammation. The missing links could be erythropoietin (EPO) and erythroferrone (ERFE), which down-regulate Hpc biosynthesis. EPO, ERFE and Hpc biosynthesis is modified by serum iron through transferrin receptor 2. Consequently, we investigated whether marathon-induced changes in EPO, ERFE and Hpc levels are blood iron-dependent. Twenty-nine healthy male marathon runners were analyzed. Serum iron, ferritin, transferrin, EPO, ERFE and Hpc levels were assessed before, immediately after, and 9 ± 2 days after the marathon. The runners whose serum Hpc decreased after the marathon (n = 15), showed a significant increase in ERFE levels. In athletes whose serum iron levels were below 105 µg/day (n = 15), serum EPO (p = 0.00) and ERFE levels (p = 0.00) increased with no changes in Hpc concentration. However, in athletes with low serum iron, no changes in EPO levels were observed when serum ferritin exceeded 70 ng/mL (n = 7). Conversely, an increase in ERFE levels was observed in marathoners with low serum iron, independently of serum ferritin (n = 7). This indicates modulation of blood iron may affect exercise-induced changes in the EPO/ERFE/Hpc axis. Further study is needed to fully understand the physiological meaning of the interdependence between iron and the EPO/ERFE/Hpc axis.