Gestational iron deficiency affects the ratio between interneuron subtypes in the postnatal cerebral cortex in mice.

Gestational iron deficiency (gID) is highly prevalent and associated with an increased risk of intellectual and developmental disabilities in affected individuals that are often defined by a disrupted balance of excitation and inhibition (E/I) in the brain. Using a nutritional mouse model of gID, we previously demonstrated a shift in the E/I balance towards increased inhibition in the brains of gID offspring that was refractory to postnatal iron supplementation. We thus tested whether gID affects embryonic progenitor cells that are fated towards inhibitory interneurons. We quantified relevant cell populations during embryonic inhibitory neuron specification and found an increase in the proliferation of Nkx2.1+ interneuron progenitors in the embryonic medial ganglionic eminence at E14 that was associated with increased Shh signaling in gID animals at E12. When we quantified the number of mature inhibitory interneurons that are known to originate from the MGE, we found a persistent disruption of differentiated interneuron subtypes in early adulthood. Our data identify a cellular target that links gID with a disruption of cortical interneurons which play a major role in the establishment of the E/I balance.

Stable iron (58Fe) isotopic measurements in Kenyan toddlers during 3 months of iron supplementation demonstrate that half of the iron absorbed is lost.

Increased iron loss may reduce the effectiveness of iron supplementation. The objective of this study was to determine if daily oral iron supplementation increases iron loss, measured using a stable isotope of iron (58Fe). We enrolled and dewormed 24 iron-depleted Kenyan children, 24-27 months of age, whose body iron was enriched and equilibrated with 58Fe given at least 1 year earlier. Over 3 months of supplementation (6 mg iron/kg body weight [BW]/day), mean (±SD) iron absorption was 1.10 (±0.28) mg/day. During supplementation, 0.55 (±0.36) mg iron/day was lost, equal to half of the amount of absorbed iron. Supplementation did not increase faecal haem/porphyrin or biomarkers of enterocyte damage and gut or systemic inflammation. Using individual patient data, we examined iron dose, absorption and loss among all available long-term iron isotopic studies of supplementation. Expressed in terms of body weight, daily iron loss was correlated significantly with iron absorption (Pearson's r = 0.66 [95% confidence interval 0.48-0.78]) but not with iron dose (r = 0.16 [95% CI -0.10-0.40]). The results of this study indicate that iron loss is increased with daily oral iron supplementation and may blunt the efficacy of iron supplements in children. This study was registered at ClinicalTrials.gov as NCT04721964.

Oral iron therapy: Current concepts and future prospects for improving efficacy and outcomes.

Iron deficiency (ID) and iron-deficiency anaemia (IDA) are global public health concerns, most commonly afflicting children, pregnant women and women of childbearing age. Pathological outcomes of ID include delayed cognitive development in children, adverse pregnancy outcomes and decreased work capacity in adults. IDA is usually treated by oral iron supplementation, typically using iron salts (e.g. FeSO4 ); however, dosing at several-fold above the RDA may be required due to less efficient absorption. Excess enteral iron causes adverse gastrointestinal side effects, thus reducing compliance, and negatively impacts the gut microbiome. Recent research has sought to identify new iron formulations with better absorption so that lower effective dosing can be utilized. This article outlines emerging research on oral iron supplementation and focuses on molecular mechanisms by which different supplemental forms of iron are transported across the intestinal epithelium and whether these transport pathways are subject to regulation by the iron-regulatory hormone hepcidin.

Iron supplementation: A qualitative study on the perception of blood donors, blood collection staff and donor physicians.

BACKGROUND AND OBJECTIVES: Iron supplementation is an effective strategy to mitigate donation-induced iron deficiency in blood donors. However, evidence on the perception of individuals involved in blood donation on iron supplementation as a blood service policy is lacking. This study aimed to evaluate the knowledge and perception of whole blood donors (donors), blood collection staff (collection staff) and donor physicians (physicians) regarding donation-induced iron loss and iron supplementation. MATERIALS AND METHODS: Online focus group discussions had four to six participants and followed a structured questioning approach. All participants had to be fluent in Dutch to participate, and donors had donated at least five times. Sixteen donors, eight collection staff members and four physicians participated in this study. Recordings were transcribed, coded and analysed using a grounded theory approach. RESULTS: Awareness of donation-induced iron loss was limited in donors. Donors and physicians were predominantly positive towards iron supplementation; the primary motivator for donors was to prevent deferral and reduce iron-deficiency-related symptoms. Improving donor health was the main argument for physicians to advocate iron supplementation. Staff had a critical view on iron supplementation as a policy, as they perceived it as unethical and possibly ineffective. A knowledge gap might underlie their concerns. CONCLUSION: Most individuals involved in blood donation are positive towards iron supplementation as a blood service policy. If implemented, guidance and monitoring is desired and adequate education of all stakeholders is required.

Donor knowledge and perceptions regarding donation-induced iron depletion and iron supplementation as a blood service policy.

BACKGROUND AND OBJECTIVES: Regular whole blood donations are associated with an increased risk of iron deficiency. Iron supplementation is an effective strategy to prevent donation-induced iron deficiency. However, research on donor perceptions towards such a policy is limited. Therefore, we aim to evaluate donors' knowledge on donation-induced iron depletion and their perceptions regarding iron supplementation as a blood service policy. MATERIALS AND METHODS: Three thousand Dutch whole blood donors were invited to complete a survey assessing their knowledge of donation-induced iron depletion and attitudes and perceptions towards iron supplementation as a policy. Linear regression modelling was used to evaluate associations between explanatory variables and perceptions. RESULTS: In total, 1093 (77.1%) donors were included in the analysis. Donors had poor knowledge of current iron management policies, but a better understanding of iron metabolism and supplementation. Iron supplementation as a policy was perceived mainly positive by donors, and the majority were willing to use iron supplements if provided. Iron supplementation was not perceived as invasive or negatively affecting donors' motivation to continue donating. Additional iron monitoring, information and donor physician involvement were regarded as important conditions for implementation. Male sex, trust in the blood service, prior experience with iron supplements and openness towards dietary supplements were strongly positively associated with willingness to use iron supplementation. CONCLUSION: Donors' knowledge regarding donation-induced iron depletion is limited, but not associated with their perceptions regarding iron supplementation. Donors do not consider iron supplementation as invasive, deterring or demotivating, and a majority are willing to take supplements if offered.

Iron status in Dutch and Finnish blood donor and general populations: A cross-cohort comparison study.

BACKGROUND AND OBJECTIVES: Blood donors are at risk of developing iron deficiency (ID) (ferritin <15 µg/L, World Health Organization definition). Blood services implement different strategies to mitigate this risk. Although in Finland risk group-based iron supplementation is in place, no iron supplementation is provided in the Netherlands. We aim to describe differences in ferritin levels and ID prevalence in donor and general populations in these countries. MATERIALS AND METHODS: Six cohorts, stratified based on sex, and for women age, in the Netherlands and Finland were used to evaluate differences in ferritin levels and ID between donor populations (Donor InSight-III and FinDonor 10,000) and general populations (Prevention of Renal and Vascular End-Stage Disease [PREVEND], FinRisk 1997 and Health 2000) and newly registered Dutch donors. Multivariable logistic regression was used to quantify associations of various explanatory factors with ID. RESULTS: In total, 13,443 Dutch and 13,933 Finnish subjects were included. Donors, except for women aged ≤50 years old in Finland, had lower median ferritin levels compared with the general population and new donors. Dutch regular blood donors had higher or similar prevalence of ID as compared with the Dutch general population, including new donors. In contrast, Finnish donors showed similar prevalence of ID compared with the general population, except for a markedly lower prevalence in ≤50-year-old women who routinely receive iron supplements when donating. CONCLUSION: Iron status in blood donors differs from that in the general population. The Finnish blood service donor management policy, for example, iron supplementation for risk groups, seemingly protects young female blood donors from developing ID.

Iron Supplementation in Management of Neurodevelopmental Disorders: Systematic Review, Meta-Analysis, and Qualitative Synthesis.

OBJECTIVE: The authors sought to explore the role of iron supplementation in the management of neurodevelopmental disorders among children and youths. METHODS: A systematic review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was undertaken. A subset of results was suitable for meta-analysis. The quality of the evidence and strength of the clinical recommendations were assessed by using the Grading of Recommendations, Assessment, Development, and Evaluation method, and critical appraisal was conducted with the Joanna Briggs Institute critical appraisal tools. RESULTS: Nine articles met inclusion criteria. These articles included studies of attention-deficit hyperactivity disorder (ADHD) (N=7), autism spectrum disorder (N=1), and Tourette's syndrome (N=1). Three randomized controlled trials evaluating iron supplementation for ADHD hyperactivity symptom severity (124 participants: placebo, N=56; supplement, N=68) met inclusion criteria for a meta-analysis. Effect sizes for the placebo and supplement groups were moderate (Cohen's d=0.76) and large (Cohen's d=1.70), respectively, although these differences were not significant. The impact of iron supplementation on inattentive ADHD symptom severity was examined in two trials (75 participants: placebo, N=31; supplement, N=44). Large, nonsignificant effect sizes were demonstrated for the placebo (Cohen's d=1.66) and supplementation (Cohen's d=3.19) groups. The quality of the evidence and strength of the clinical recommendations were considered very low. CONCLUSIONS: Further research is needed to examine the role of iron supplementation in the management of ADHD and neurodevelopmental disorders more generally. Additionally, iron supplementation comes with risks, including death in the case of overdose.

Ferritin and iron supplements in gestational diabetes mellitus: less or more?

Iron metabolism has been found to be closely related to gestational diabetes mellitus (GDM). Excessive ferritin levels were shown to be related to an increased risk of GDM because of iron overload which may lead to insulin resistance and ß-cell injury by enhancing oxidative stress and inflammatory responses. On the contrary, insufficient ferritin levels can cause a number of obstetric complications, such as high incidence rates of anaemia and gestational hypertension. Therefore, high or low ferritin levels may have adverse effects on the mother and the foetus, putting clinicians in a dilemma when giving pregnant women iron supplements. This also explains why there have been more conflicting findings in the studies on dietary or oral iron supplementation during pregnancy. Hence, there is an urgent need for more evidence and strategies for appropriate recommendations for ferritin levels and iron supplementation during pregnancy to prevent iron insufficiency without causing iron overload and increasing the risk of GDM. Therefore, we gave an updated review on the association of GDM with ferritin metabolism, ferritin levels and iron supplementation based on the summary of the latest research.

A review of the effect of iron supplementation on the gut microbiota of children in developing countries and the impact of prebiotics.

Iron is essential for many physiological functions of the body, and it is required for normal growth and development. Iron deficiency (ID) is the most common form of micronutrient malnutrition and is particularly prevalent in infants and young children in developing countries. Iron supplementation is considered the most effective strategy to combat the risk of ID and ID anaemia (IDA) in infants, although iron supplements cause a range of deleterious gut-related problems in malnourished children. The purpose of this review is to assess the available evidence on the effect of iron supplementation on the gut microbiota during childhood ID and to further assess whether prebiotics offer any benefits for iron supplementation. Prebiotics are well known to improve gut-microbial health in children, and recent reports indicate that prebiotics can mitigate the adverse gut-related effects of iron supplementation in children with ID and IDA. Thus, provision of prebiotics alongside iron supplements has the potential for an enhanced strategy for combatting ID and IDA among children in the developing world. However, further understanding is required before the benefit of such combined treatments of ID in nutritionally deprived children across populations can be fully confirmed. Such enhanced understanding is of high relevance in resource-poor countries where ID, poor sanitation and hygiene, alongside inadequate access to good drinking water and poor health systems, are serious public health concerns.

Iron supplementation in the diets of hybrid catfish (Ictalurus punctatus × I. furcatus) juveniles affected haematocrit levels and potentially decreased disease resistance to Edwardsiella ictaluri.

To prevent catfish idiopathic anaemia, diets fortified with iron have been adopted as a regular practice on commercial catfish farms to promote erythropoiesis. However, the effects of prolonged exposure of excess dietary iron on production performance and disease resistance for hybrid catfish (Ictalurus punctatus × I. furcatus) remains unknown. Four experimental diets were supplemented with ferrous monosulphate to provide 0, 500, 1000, and 1500 mg of iron per kg of diet. Groups of 16 hybrid catfish juveniles (~22.4 g) were stocked in each of 20, 110-L aquaria (n = 5), and experimental diets were offered to the fish to apparent satiation for 12 weeks. At the end of the study, production performance, survival, condition indices, as well as protein and iron retention were unaffected by the dietary treatments. Blood haematocrit and the iron concentration in the whole-body presented a linear increase with the increasing the dietary iron. The remaining fish from the feeding trial was challenged with Edwardsiella ictaluri. Mortality was mainly observed for the dietary groups treated with iron supplemented diets. The results for this study suggest that iron supplementation beyond the required levels does affect the blood production, and it may increase their susceptibility to E. ictaluri infection.

Does oral iron and folate supplementation during pregnancy protect against adverse birth outcomes and reduced neonatal and infant mortality in Africa: A protocol for a systematic review and meta-analysis?

BACKGROUND: Globally, one-third of pregnant women are at risk of iron deficiency, particularly in the African region. While recent findings show that iron and folate supplementation can lower the risk of adverse birth outcomes and childhood mortality, our understanding of its impact in Africa remains incomplete due to insufficient evidence. This protocol outlines the systematic review steps to investigate the impact of oral iron and folate supplementation during pregnancy on adverse birth outcomes, neonatal mortality and infant mortality in Africa. METHODS AND ANALYSIS: MEDLINE, PsycINFO, Embase, Scopus, CINAHL, Web of Science, and Cochrane databases were searched for published articles. Google Scholar and Advanced Google Search were used for gray literature and nonindexed articles. Oral iron and/or folate supplementation during pregnancy is the primary exposure. The review will focus on adverse birth outcomes, neonatal mortality and infant mortality. Both Cochrane Effective Practice and Organization of Care and Newcastle-Ottawa Scale risk of bias assessment tools will be used. Meta-analysis will be conducted if design and data analysis methodologies permit. This systematic review and meta-analysis will provide up-to-date evidence about iron and folate supplementation's role in adverse birth outcomes, neonatal mortality and infant mortality in the African region. ETHICS AND DISSEMINATION: This review will provide insights that help policymakers, program planners, researchers, and public health practitioners interested in working in the region. PROSPERO REGISTRATION NUMBER: CRD42023452588.

Iron Metabolism in the Recovery Phase of Critical Illness with a Focus on Sepsis.

Iron is an essential nutrient for humans and microbes, such as bacteria. Iron deficiency commonly occurs in critically ill patients, but supplementary iron therapy is not considered during the acute phase of critical illness since it increases iron availability for invading microbes and oxidative stress. However, persistent iron deficiency in the recovery phase is harmful and has potential adverse outcomes such as cognitive dysfunction, fatigue, and cardiopulmonary dysfunction. Therefore, it is important to treat iron deficiency quickly and efficiently. This article reviews current knowledge about iron-related biomarkers in critical illness with a focus on patients with sepsis, and provides possible criteria to guide decision-making for iron supplementation in the recovery phase of those patients.

Iron Supplementation of Pregnant Sows to Prevent Iron Deficiency Anemia in Piglets: A Procedure of Questionable Effectiveness.

In pigs, iron deficiency anemia (IDA) is a common disorder that occurs during the early postnatal period, leading to the stunted growth and increased mortality of piglets. The main cause of IDA is low iron stores in the liver of newborn piglets; these stores constitute the main source of iron needed to satisfy the erythropoietic requirements of the piglets in their first weeks of life. Insufficient iron stores in piglets are usually due to the inadequate placental iron transfer from the sow to the fetuses. Therefore, iron supplementation in pregnant sows has been implemented to enhance placental iron transfer and increase iron accumulation in the liver of the fetuses. Over the years, several oral and parenteral approaches have been attempted to supplement sows with various iron preparations, and consequently, to improve piglets' red blood cell indices. However, there is debate with regard to the effectiveness of iron supplementation in pregnant sows for preventing IDA in newborn piglets. Importantly, this procedure should be carried out with caution to avoid iron over-supplementation, which can lead to iron toxicity. This article aims to critically review and evaluate the use of iron supplementation in pregnant sows as a procedure for preventing IDA in piglets.

Iron Deficiency in Pulmonary Hypertension.

Pulmonary hypertension (PH) is a complex cardiovascular condition that is characterized by elevated pulmonary arterial pressure, which leads to significant morbidity and mortality. Among the various factors that influence the pathophysiology and progression of PH, iron deficiency has become a critical, yet often overlooked, element. In this review, the prevalence, implications, and therapeutic potential of addressing iron deficiency in patients with PH are elucidated.Iron deficiency, which is prevalent in a significant proportion of patients with PH, has been associated with worsened clinical outcomes, including diminished exercise capacity, impaired oxygen transport and utilization, and compromised right ventricular function. The pathophysiological linkages between iron deficiency and PH are multifaceted and involve alterations in oxygen sensing, endothelial function, and metabolic disturbances.In this review, the evidence from recent clinical trials and studies that assess the impact of iron supplementation, both oral and intravenous, on PH outcomes is critically analyzed. Although some studies suggest improvements in exercise capacity and hemodynamic parameters following iron repletion, the responses appear variable and are not universally beneficial. This review highlights the complexities of iron metabolism in PH and the challenges in effectively diagnosing and treating iron deficiency in this patient population.Furthermore, the potential mechanisms through which iron supplementation might influence pulmonary vascular and right ventricular function, emphasizing the need for personalized treatment approaches are discussed. In this review, the importance of recognizing iron deficiency in the management of patients with PH is highlighted, and further research is warranted to establish comprehensive, evidence-based guidelines for iron supplementation in this unique patient cohort. The ultimate goal of this review is to improve clinical outcomes and quality of life for patients suffering from this debilitating condition.

Prenatal iron supplementation adjusted to maternal iron stores reduces behavioural problems in 4-year-old children.

Prenatal iron supplementation improves children's health and cognitive performance, but few studies explore behavioural development. This study assessed the effects of adjusting prenatal iron supplementation to maternal iron stores during early pregnancy on children's behavioural problems. Randomized controlled trial conducted in Tarragona (Spain) involving 230 nonanaemic pregnant women and their children after a 4-year follow-up. Based on haemoglobin (Hb) levels before gestational week (GW) 12, women receive different iron doses: those with Hb = 110-130 g/L were randomized to receive 80 or 40 mg/day and those with Hb > 130 g/L were randomized to receive 20 or 40 mg/day. Maternal iron stores at GW12 were classified using serum ferritin (SF) as low (SF < 15 µg/L), normal (SF = 15-65 µg/L), and normal-high (SF > 65 µg/L). Children's behaviour was assessed by parents using the Child Behaviour Checklist for ages 1.5-5 years and the Behaviour Rating Inventory of Executive Function-Preschool Version, and by teachers using the Teacher's Report Form for ages 1.5-5 years. Multivariable regression models were performed. Taking 80 mg/day of iron improved child behaviour when women had low iron stores but worsened it when mothers had normal-high iron stores, except for depressive and attention/hyperactivity problems. Taking 20 mg/day of iron improved behaviour only in those children whose mothers had SF > 65 µg/L in early pregnancy. Additionally, executive functioning improved at high doses of prenatal iron when maternal baseline SF < 15 µg/L. Adjusting prenatal iron supplementation to both maternal baseline Hb levels and iron stores reduces behavioural problems in 4-year-old children.

The Effects of Iron Administration on Anemia Development during the 7th and 21st Day of Life in Premature Newborns: A Prospective Cohort Study.

Background and Objectives: The administration of iron to premature newborns is a common intervention aimed at preventing iron deficiency (ID). However, there is no consensus on the optimal timing and dosage for iron supplementation in this population. This study evaluates the effects and potential adverse outcomes of administering iron on the 7th and 21st days of life in premature infants. Materials and Methods: This research was conducted on 108 premature neonates at the "Louis Turcanu" Children's Emergency Clinical Hospital in Timisoara, Romania. The study population was divided into a control group of 48 newborns who did not receive iron supplementation and an intervention group of 60 newborns who did. The analysis utilized univariate and multivariate regression to examine binary outcomes. Results: The findings indicate that iron supplementation significantly increased the risk of anemia during the premature period at 21 days of life, as demonstrated by both univariate and multivariate regression analyses, with an odds ratio (OR) of 2.40 (95% CI, 1.01-5.68) and an adjusted odds ratio (AOR) of 2.75 (95% CI, 1.06-7.11), respectively. Contrary to expectations, iron supplementation did not significantly alter the risk of abnormal serum ferritin or iron levels at 21 days of life, according to the univariate analysis (p = 0.380 and p = 0.526, respectively). Conclusions: The observed increase in the risk of anemia without a corresponding improvement in the serum ferritin or iron levels suggests the need for further investigation into alternative strategies for iron supplementation in premature newborns.

The Interactions between Maternal Iron Supplementation and Iron Metabolism-Related Genetic Polymorphisms on Birth Outcomes: A Prospective Study in Chinese.

BACKGROUND: The effect of iron supplementation during pregnancy on birth outcomes may vary with maternal genetic background and needs more investigation. OBJECTIVES: This prospective study aimed to evaluate the interactions between maternal iron supplementation and iron metabolism-related genetic polymorphisms on birth outcomes. METHODS: This was a substudy from a community-based randomized control trial conducted in Northwest China, which included 860 women from the 2 micronutrient supplementation groups (folic acid [FA] and FA + iron group). Maternal peripheral blood, sociodemographic and health-related information, and neonatal birth outcomes were collected. Six single nucleotide polymorphisms in iron metabolism-related genes were genotyped. The alleles associated with decreased iron/hemoglobin status were used as the effect alleles. The genetic risk score (GRS) that reflected the genetic risk of low iron/hemoglobin status was estimated using the unweighted and weighted methods. Generalized estimating equations with small-sample corrections were applied to evaluate the interactions between iron supplementation and SNPs/GRS on birth outcomes. RESULTS: There were significant interactions between maternal iron supplementation and rs7385804 (P = 0.009), rs149411 (P = 0.035), rs4820268 (P = 0.031), the unweighted GRS (P = 0.018), and the weighted GRS (P = 0.009) on birth weight. Compared with FA supplementation only, FA + iron supplementation significantly increased birth weight among women with more effect alleles in rs7385804 (ß: 88.8 g, 95% CI: 9.2, 168.3) and the GRSs (the highest unweighted GRS, ß: 135.5 g, 95% CI: 7.7, 263.4; the highest weighted GRS, ß: 145.9 g, 95% CI: 43.4, 248.5); it had a trend of decreasing birth weight and increasing low birth weight risk among women with fewer effect alleles. CONCLUSIONS: In our population, maternal genetic background related to iron metabolism plays a significant role in determining the efficacy of iron supplementation. Routine iron supplementation could be more beneficial to fetal weight growth among mothers with higher genetic risk for low iron/hemoglobin status.

The effect of ferritin-guided iron supplementation among Danish female first-time blood donors.

BACKGROUND: The identification of blood donors at risk of developing low hemoglobin (Hb) and subsequent intervention is expected to reduce donation-induced iron deficiency and low Hb among blood donors. This study explores the effects of ferritin-guided iron supplementation for female first-time donors implemented in four of five administrative regions in Denmark. STUDY DESIGN AND METHODS: We included 45,919 female first-time donors in this study. Hb values were determined in donations of included donors during a 2-year follow-up period. For each region, an intervention group (after implementation) and a control group (before implementation) were defined. The primary outcome was Hb below the donation threshold (7.8 mmol/L ~ 12.5 g/dL) at the time of donation, in the control group, and the intervention group, using logistic regression. The secondary outcome was the number of donations per donor given during the follow-up period. RESULTS: We observed a statistically significant decrease in the risk of female first-time donors experiencing a donation with low Hb after ferritin-guided iron supplementation was introduced: Odds ratio, 0.82; 95% confidence interval (CI), 0.71-0.95. We found a statistically significant increase in the number of donations per donor during the follow-up period after intervention; rate ratio: 1.05, 95% CI: 1.02-1.08. DISCUSSION: Ferritin-guided iron supplementation led to a significant reduction in the occurrence of low hemoglobin (Hb) levels among Danish female first-time blood donors. The intervention was additionally associated with an increase in the number of donations per donor.

Validity of donor-reported iron supplementation practices obtained at the time of donation.

BACKGROUND: Iron supplementation (IS) improves blood donors' iron stores and allows more frequent blood donation. Understanding the accuracy of self-reported IS is helpful for potential application of IS practices to donor eligibility or donation intervals. METHODS: Successful whole blood and red cell apheresis donors completed a survey at donation on the use of select dietary supplements. Respondents reporting use of either iron pills (IP) or multivitamins (MV) were invited by email to complete a similar follow-up survey 6-8 weeks later and to provide the quantitative iron content of IS by referring the donor to the pill bottle label. Consistency between baseline and follow-up responses was assessed overall and by pill type and demographic variables. RESULTS: Of 2444 donors answering the baseline survey, 40% (978) reported MV or IP at donation, 354 of whom completed the follow-up survey. A majority of survey respondents (56%-61%) reported taking iron across the two surveys, and 21%-24% took MV but were uncertain if their pills contained iron. Of 215 reporting IS at baseline, overall concordance at follow-up was 68% and was higher for donors who were female, ≥50-years old, and taking iron as an iron pill rather than in a multivitamin. CONCLUSION: Consistency of donor responses may be insufficient for use in guiding donor eligibility. Referring donors to their pill bottles was unsuccessful in improving the high frequency of uncertain responses. Incorporating IS into donor eligibility determinations is a complex endeavor that will benefit from careful planning and from post-implementation monitoring.

Association between serum iron markers, iron supplementation and cardiovascular morbidity in pre-dialysis chronic kidney disease.

BACKGROUND: The optimal range of serum iron markers and usefulness of iron supplementation are uncertain in patients with pre-dialysis chronic kidney disease (CKD). We investigated the association between serum iron indices and risk of cardiovascular disease (CVD) events and the effectiveness of iron supplementation using Chronic Kidney Disease Japan Cohort data. METHODS: We included 1416 patients ages 20-75 years with pre-dialysis CKD. The tested exposures were serum transferrin saturation and serum ferritin levels and the outcome measures were any cardiovascular event. Fine-Gray subdistribution hazard models were used to examine the association between serum iron indices and time to events. The multivariable fractional polynomial interaction approach was used to evaluate whether serum iron indices were effect modifiers of the association between iron supplementation and cardiovascular events. RESULTS: The overall incidence rate of CVD events for a median of 4.12 years was 26.7 events/1000 person-years. Patients with serum transferrin saturation <20% demonstrated an increased risk of CVD [subdistribution hazard ratio (HR) 2.13] and congestive heart failure (subdistribution HR 2.42). The magnitude of reduction in CVD risk with iron supplementation was greater in patients with lower transferrin saturations (P = .042). CONCLUSIONS: Maintaining transferrin saturation >20% and adequate iron supplementation may effectively reduce the risk of CVD events in patients with pre-dialysis CKD.