Anaemia in cardiac surgery - a retrospective review of a centre's experience with a pre-operative intravenous iron clinic.

Pre-operative anaemia is associated with higher rates of transfusion and worse outcomes, including prolonged hospital stay, morbidity and mortality. Iron deficiency is associated with significantly lower haemoglobin levels throughout the peri-operative period and more frequent blood transfusion. Correction of iron stores before surgery forms part of the first pillar of patient blood management. We established a pre-operative anaemia clinic to aid identification and treatment of patients with iron deficiency anaemia scheduled for elective cardiac surgery. We present a retrospective observational review of our experience from January 2017 to December 2019. One-hundred and ninety patients received treatment with intravenous iron, a median of 21 days before cardiac surgery. Of these, 179 had a formal laboratory haemoglobin level measured before surgery, demonstrating a median rise in haemoglobin of 8.0 g.l-1 . Patients treated with i.v. iron demonstrated a significantly higher incidence of transfusion (60%) compared with the non-anaemic cohort (22%) during the same time period, p < 0.001. Significantly higher rates of new requirement for renal replacement therapy (6.7% vs. 0.6%, p < 0.001) and of stroke (3.7% vs. 1.2%, p = 0.010) were also seen in this group compared with those without anaemia, although there was no significant difference in in-hospital mortality (1.6% vs. 0.8%, p = 0.230). In patients where the presenting haemoglobin was less than 130 g.l-1 , but there was no intervention or treatment, there was no difference in rates of transfusion or of complications compared with the anaemic group treated with iron. In patients with proven iron deficiency anaemia, supplementation with intravenous iron showed only a modest effect on haemoglobin and this group still had a significantly higher transfusion requirement than the non-anaemic cohort. Supplementation with intravenous iron did not improve outcomes compared with patients with anaemia who did not receive intravenous iron and did not reduce peri-operative risk to non-anaemic levels. Questions remain regarding identification of patients who will receive most benefit, the use of concomitant treatment with other agents, and the optimum time frames for treatment in order to produce benefit in the real-world setting.

Rationale and design of the AFFIRM-AHF trial: a randomised, double-blind, placebo-controlled trial comparing the effect of intravenous ferric carboxymaltose on hospitalisations and mortality in iron-deficient patients admitted for acute heart failure.

AIMS: Iron deficiency (ID) is a common co-morbidity in heart failure (HF), associated with impaired functional capacity, poor quality of life and increased morbidity and mortality. Treatment with intravenous (i.v.) ferric carboxymaltose (FCM) has shown improvements in functional capacity, symptoms and quality of life in stable HF patients with reduced ejection fraction. The effect of i.v. iron supplementation on morbidity and mortality in patients hospitalised for acute HF (AHF) and who have ID has yet to be established. The objective of the present article is to present the rationale and design of the AFFIRM-AHF trial (ClinicalTrials.gov NCT02937454) which will investigate the effect of i.v. FCM (vs. placebo) on recurrent HF hospitalisations and cardiovascular (CV) mortality in iron-deficient patients hospitalised for AHF. METHODS: AFFIRM-AHF is a multicentre, randomised (1:1), double-blind, placebo-controlled trial which recruited 1100 patients hospitalised for AHF and who had iron deficiency ID defined as serum ferritin <100 ng/mL or 100-299 ng/mL if transferrin saturation <20%. Eligible patients were randomised (1:1) to either i.v. FCM or placebo and received the first dose of study treatment just prior to discharge for the index hospitalisation. Patients will be followed for 52 weeks. The primary outcome is the composite of recurrent HF hospitalisations and CV mortality. The main secondary outcomes include the composite of recurrent CV hospitalisations and CV mortality, recurrent HF hospitalisations and safety-related outcomes. CONCLUSION: The AFFIRM-AHF trial will evaluate, compared to placebo, the effect of i.v. FCM on morbidity and mortality in iron-deficient patients hospitalised for AHF.

Suspecting Hyperferritinemic Sepsis in Iron-Deficient Population: Do We Need a Lower Plasma Ferritin Threshold?

OBJECTIVES: Hyperferritinemia is being suggested to identify patients with sepsis-induced macrophage activation syndrome for early intervention. However, data among iron-deficient children are scarce. This study was planned to explore the biological behavior of plasma ferritin in children from communities with a high frequency of iron deficiency with septic shock and its association with the outcome. DESIGN: Prospective observational study. SETTING: Tertiary care teaching hospital in a low-middle income economy of South Asia. PATIENTS OR SUBJECTS: Patients (6 mo to 12 yr) (n = 42) with septic shock and their healthy siblings as controls (n = 36). Patients/controls with blood transfusion/iron supplement during last 6 months or with any chronic disease were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Ferritin was measured in patients at enrollment and then at 1 month of hospital discharge while they were not on iron supplementation and in controls as indicative of baseline level. Patients' median age was 30 months (13.5-87 mo), 31% were malnourished, majority (86%) had anemia, and two thirds had microcytic hypochromic red cells. Ferritin at admission was 763 ng/mL (480-1,820 ng/mL) in nonsurvivors, whereas 415 ng/mL (262-852 ng/mL) in survivors (p = 0.11). Pediatric Logistic Organ Dysfunction score and C-reactive protein correlated positively with plasma ferritin (p = 0.03 and p = 0.01, respectively) at enrollment. Elevated ferritin of greater than 500 ng/mL (relative risk, 2.48; 95% CI, 0.95-6.43) and greater than 1,000 ng/mL (relative risk, 1.94; 95% CI, 0.94-4.02) were associated with higher mortality but not independently. Among survivors, the 1-month follow-up ferritin fell significantly to 97 ng/mL (16-118 ng/mL) (p = 0.001). However, it was still significantly higher than that in sibling controls (19 ng/mL [10-54 ng/mL]) (p = 0.003). CONCLUSIONS: Ferritin rises significantly in septic shock patients despite iron deficiency and seems to correlate with the severity of inflammation and organ dysfunction. Even a lower threshold (of 500 or 1,000 ng/mL) could predict higher mortality. It may suggest the need for redefining the plasma ferritin threshold for suspecting hyperferritinemic sepsis and sepsis-induced macrophage activation syndrome in these patients. Larger studies with frequent ferritin measurements are desirable to validate these initial observations.

A 5-Year Follow-Up of Study Patients With Asymptomatic Iron-Deficiency Anemia Using a Nurse-Led Pathway.

A protocol-driven, systematic pathway was developed to allow rapid and coordinated investigation of patients with iron-deficiency anemia (IDA) in a nurse-delivered outpatient setting. The study objective was to assess the safety and efficacy of the pathway by 5-year outcome data for the exclusion of gastrointestinal (GI) malignancy. This is a 5-year follow-up study of 122 patients entered onto the pathway with negative initial upper and lower GI investigations. The study was conducted at Hereford County Hospital NHS Trust (a district general hospital serving 220,00 people). Clinical outcomes of patients at 5 years and service efficiency at detecting relevant pathology were observed. A total of 272 patients were investigated through the pathway, and in 150 patients a GI cause for IDA was found. We established the outcome in 97% of the 122 patients with normal GI investigation at 5 years after their initial investigation. Of the 118 patients followed up, 92 patients were alive and well and 26 had died or developed malignancy. With the exception of diabetes (odds ratio 0.24; 95% confidence interval [0.1, 0.8]; p = .02), no features were found to be a significant risk factor for poor prognosis, including age, gender, hemoglobin level, anemia at 3 months, or other comorbidities. Three patients developed colonic malignancy; two patients had diverticular disease at barium enema and presented 4 years later with colorectal cancer. One patient declined lower GI investigation and presented with metastatic colon cancer on computed tomography scan at 1 year. No other GI cancers were diagnosed. Our nurse-delivered, protocol-driven pathway is a highly effective and safe system for the exclusion of GI cancer within 5 years of follow-up.

Anaemia management and mortality risk in newly visiting patients with chronic kidney disease in Japan: The CKD-ROUTE study.

AIM: To investigate the association between iron deficiency anaemia and mortality risk and assess the changes in anaemia and iron status after primary management by a nephrologist. METHODS: In this prospective cohort study, we stratified 951 non-dialysis chronic kidney disease (CKD) G2-G5 patients newly visiting 16 nephrology centres into four groups according to the presence of anaemia with or without iron deficiency. All-cause mortality, cardiovascular (CV)-related mortality, and a change in anaemia and iron status after specialized primary care were the endpoints evaluated. RESULTS: During a median follow-up time of 19 months, the number of all-cause deaths and CV-related deaths were 56 and 26, respectively. Compared with the control group, the groups with isolated anaemia and iron deficiency anaemia had significantly higher all-cause mortalities (isolated anaemia: hazard ratio (HR), 3.37; 95% confidence intervals (CI), 1.76-6.44; iron deficiency anaemia: HR, 3.11; 95% CI, 1.21-8.01) and CV-related mortalities (isolated anaemia: HR, 3.64; 95% CI, 1.36-9.73; iron deficiency anaemia: HR, 3.86; 95% CI, 1.11-13.41). In the isolated anaemia group, erythropoietin-stimulating agent (ESA) prescriptions significantly increased to approximately 70%. However, in patients with both anaemia and iron deficiency, iron prescriptions only increased to 48.1%. CONCLUSIONS: Iron deficiency anaemia and isolated anaemia were associated with all-cause and CV-related mortality. The absence of relative increase in iron prescriptions suggests that iron deficiency should be accurately assessed and iron supplementation should be appropriately used to manage anaemia in non-dialysis patients with CKD.

The impact of anemia on child mortality: an updated review.

Iron deficiency anemia and child mortality are public health problems requiring urgent attention. However, the degree to which iron deficiency anemia contributes to child mortality is unknown. Here, we utilized an exhaustive article search and screening process to identify articles containing both anemia and mortality data for children aged 28 days to 12 years. We then estimated the reduction in risk of mortality associated with a 1-g/dL increase in hemoglobin (Hb). Our meta-analysis of nearly 12,000 children from six African countries revealed a combined odds ratio of 0.76 (0.62-0.93), indicating that for each 1-g/dL increase in Hb, the risk of death falls by 24%. The feasibility of a 1-g/dL increase in Hb has been demonstrated via simple iron supplementation strategies. Our finding suggests that ~1.8 million deaths in children aged 28 days to five years could be avoided each year by increasing Hb in these children by 1 g/dL.

Global burden and significance of multiple micronutrient deficiencies in pregnancy.

Maternal mortality, low birthweight infants and childhood stunting continue to be major global public health problems, part of a recurring cycle of disadvantage. Maternal undernutrition in particular is one of the most neglected aspects of nutrition in public health. One possible low-cost public health intervention that might help address these problems is the antenatal provision of multiple micronutrient supplements. If the evidence base could be established, cost-effectiveness found to be acceptable and safety ensured, supplementation could ameliorate the impact of poor nutrition and diets, high disease burdens and the sociocultural factors contributing to these problems. There have been good studies in over a dozen countries addressing some of these issues but with conflicting results. Consequently, at least three meta-analyses have been undertaken to establish significant findings that could help guide policies and programs. They concluded that multimicronutrient supplementation improves birthweight and likely reduces the number of infants born low birthweight. Supplementation with iron-folic acid or multimicronutrients also appears to have positive longer-term impacts on the health and development of the offspring. There remain concerns about possible increased infant mortality in some populations. Given the results of the meta-analyses, cautious scaling-up of country effectiveness trials appears justified with careful monitoring and evaluation.

Intervention strategies to address multiple micronutrient deficiencies in pregnancy and early childhood.

Deficiencies of multiple micronutrients are prevalent among women of reproductive age and young children, and represent a risk factor for increased morbidity and mortality in these women and children. The role of multiple micronutrient supplementation during pregnancy and early childhood has been evaluated in randomized trials. Multiple micronutrient supplementation during pregnancy has a positive effect on birthweight and reduces prevalence of low birthweight and small for gestational age babies. It had comparable effects on prevalence of anemia regarding iron-folate supplementation. Multiple micronutrient supplementations in children have been shown to improve linear growth, weight, hemoglobin, serum zinc, serum retinol levels and motor development. Some of the most commonly used strategies to deliver multiple micronutrients include powders (e.g. Sprinkles(®)), crushable tablets (e.g. Foodlets), etc. Multiple micronutrient supplementation during pregnancy and early childhood seems to be an effective way of prevention of micronutrient deficiencies and has a significant protective effect against adverse outcomes related to their deficiencies. Their use on a larger scale should be considered to improve the survival and decrease morbidity and mortality in children and women.

Iron and folic acid supplements in pregnancy improve child survival in Indonesia.

BACKGROUND: Several trials have shown that iron-folic acid supplements during pregnancy protect newborns against preterm delivery and early neonatal death, but the impact beyond the neonatal period is unclear. OBJECTIVE: We determined whether live-born children <5 y of age born to mothers who used antenatal iron-folic acid supplements had reduced risk of death. DESIGN: Pooled 1994, 1997, 2002-2003, and 2007 Indonesia Demographic and Health Survey data were used to examine the relation between the use of iron-folic acid supplements and child death in 3 cumulative (0-30 d, 0-11 mo, and 0-4 y) and 4 mutually exclusive (first day of life and 1-30 d, 1-11 mo, and 1-4 y of age) time periods. Risk of death was estimated by using Cox regression to control for 19 potential confounders. RESULTS: Survival information for 52,917 singleton live-born infants and 1525 deaths of children <5 y of age was examined. After adjustment for potential confounders, risk of death of children <5 y of age was reduced significantly by 34% if the mother consumed any iron-folic acid supplements [adjusted HR (aHR): 0.66; 95% CI: 0.53, 0.81; P < 0.001]. This protective effect was greatest for deaths on the first day of life (aHR: 0.40; 95% CI: 0.21, 0.77; P = 0.005) but was also shown for neonatal deaths on days 1-30 of life (aHR: 0.69; 95% CI: 0.49, 0.97; P = 0.035) and postneonatal deaths (aHR: 0.74; 95% CI: 0.56, 0.99; P = 0.044). There was a strong dose response of greater protection from death of children <5 y of age with increasing numbers of iron-folic acid supplements consumed. CONCLUSION: In developing countries increased use of antenatal iron-folic acid supplements will reduce deaths of children <5 y of age, especially in the first year of life.

Efficacy and safety of iron supplementation for the elderly patients undergoing hip or knee surgery: a meta-analysis of randomized controlled trials.

BACKGROUND: Anemia is a frequent co-morbidity in the elderly patients undergoing hip or knee surgery and is often associated with poor clinical outcomes. Mild to moderate anemia is often treated with intravenous or oral iron supplementation. However, the efficacy and safety of iron supplementation in treating anemia for the elderly patients undergoing hip or knee surgery remains controversial. METHODS: Only prospective, randomized studies that compared iron supplementation with no iron supplementation in the elderly patients undergoing hip or knee surgery were included. Six studies met the inclusion criteria: the target population consisted of patients undergoing hip or knee surgery treated with iron supplementation; the study was a published randomized trial. Each outcome measure tested was assessed for heterogeneity. If significant heterogeneity was present for more than 75%, data from the studies were not combined. If there was no significant heterogeneity (less than 40%), a weighted mean difference (WMD) or combined relative risk was calculated using a fixed effects model, while a random effects model was applied when heterogeneity was within 40% to 75%. RESULTS: Our meta-analysis demonstrated the increase of hemoglobin level in patients undergoing hip or knee surgery with iron supplementation. However, no significant difference on the length of hospital stay, morbidity, 1-mo mortality, the infection rate, the rate and volume of allogeneic blood transfusions, and the adverse drug effects was found between the patients with iron treatment and those without. CONCLUSION: Our meta-analysis suggested that iron supplementation was safe and effective in treating anemia for the elderly patients undergoing hip or knee surgery.

Maternal iron-folic acid supplementation programs: evidence of impact and implementation.

BACKGROUND: According to a World Health Organization (WHO) review of nationally representative surveys from 1993 to 2005, 42% of pregnant women have anemia worldwide. Almost 90% of anemic women reside in Africa or Asia. Most countries have policies and programs for prenatal iron-folic acid supplementation, but coverage remains low and little emphasis is placed on this intervention within efforts to strengthen antenatal care services. The evidence of the public health impact of iron-folic acid supplementation and documentation of the potential for scaling up have not been reviewed recently. OBJECTIVE: The purpose of this review is to examine the evidence regarding the impact on maternal mortality of iron-folic acid supplementation and the evidence for the effectiveness of this intervention in supplementation trials and large-scale programs. METHODS: The impact on mortality is reviewed from observational studies that were analyzed for the Global Burden of Disease Analysis in 2004. Reviews of iron-folic acid supplementation trials were analyzed by other researchers and are summarized. Data on anemia reduction from two large-scale national programs are presented, and factors responsible for high coverage with iron-folic acid supplementation are discussed. RESULTS: Iron-deficiency anemia underlies 115,000 maternal deaths per year. In Asia, anemia is the second highest cause of maternal mortality. Even mild and moderate anemia increase the risk of death in pregnant women. Iron-folic acid supplementation of pregnant women increases hemoglobin by 1.17 g/dL in developed countries and 1.13 g/dL in developing countries. The prevalence of maternal anemia can be reduced by one-third to one-half over a decade if action is taken to launch focused, large-scale programs that are based on lessons learned from countries with successful programs, such as Thailand and Nicaragua. CONCLUSIONS: Iron-folic acid supplementation is an under-resourced, affordable intervention with substantial potential for contributing to Millennium Development Goal 5 (maternal mortality reduction) in countries where iron intakes among pregnant women are low and anemia prevalence is high. This can be achieved in the near term, as policies are already in place in most countries and iron-folic acid supplements are already in lists of essential drugs. What is needed is to systematically adopt lessons about how to strengthen demand and supply systems from successful programs.

Predictors and consequences of anaemia among antiretroviral-naïve HIV-infected and HIV-uninfected children in Tanzania.

OBJECTIVE: Predictors and consequences of childhood anaemia in settings with high HIV prevalence are not well known. The aims of the present study were to identify maternal and child predictors of anaemia among children born to HIV-infected women and to study the association between childhood anaemia and mortality. DESIGN: Prospective cohort study. Maternal characteristics during pregnancy and Hb measurements at 3-month intervals from birth were available for children. Information was also collected on malaria and HIV infection in the children, who were followed up for survival status until 24 months after birth. SETTING: Dar es Salaam, Tanzania. SUBJECTS: The study sample consisted of 829 children born to HIV-positive women. RESULTS: Advanced maternal clinical HIV disease (relative risk (RR) for stage > or =2 v. stage 1: 1.31, 95 % CI 1.14, 1.51) and low CD4 cell counts during pregnancy (RR for <350 cells/mm3 v. > or =350 cells/mm3: 1.58, 95 % CI 1.05, 2.37) were associated with increased risk of anaemia among children. Birth weight <2500 g, preterm birth (<34 weeks), malaria parasitaemia and HIV infection in the children also increased the risk of anaemia. Fe-deficiency anaemia in children was an independent predictor of mortality in the first two years of life (hazard ratio 1.99, 95 % CI 1.06, 3.72). CONCLUSIONS: Comprehensive care including highly active antiretroviral therapy to eligible HIV-infected women during pregnancy could reduce the burden of anaemia in children. Programmes for the prevention of mother-to-child transmission of HIV and antimalarial treatment to children could improve child survival in settings with high HIV prevalence.

Treatment of transfusional iron overload in patients with myelodysplastic syndrome or severe anemia: data from multicenter clinical practices.

BACKGROUND: Patients with myelodysplastic syndrome (MDS) or severe anemia requiring repeated red blood cell (RBC) transfusions risk developing transfusional iron overload, which can reduce survival. Iron chelation therapy (ICT) has been shown to improve survival and quality of life in patients; however, ICT utilization in clinical practices is not well understood. STUDY DESIGN AND METHODS: Medical records of patients diagnosed with MDS or severe anemia at least 6 months before data extraction, aged at least 21 years at diagnosis, and who received at least one RBC transfusion were reviewed. ICT eligibility was defined as at least 20 units of RBCs transfused or at least two serum ferritin levels exceeding 1000 microg/L. Study endpoint was ICT treatment rate among ICT-eligible patients with lower-risk MDS (International Prognostic Scoring System [low or intermediate-1]; World Health Organization [refractory anemia {RA}, refractory anemia with ringed sideroblasts {RARS}, refractory cytopenia with multilineage dysplasia {RCMD}, refractory cytopenia with multilineage dysplasia and ringed sideroblasts, or 5q]; French-American-British [RA/RARS]). RESULTS: Among 78 ICT-eligible patients with lower-risk MDS, 32 (41%) received ICT. At ICT initiation, treated patients received on average 13.3 transfusions (27.6 units) and mean first post-ICT initiation serum ferritin was twice the MDS Foundation recommendation at 1949 microg/L. Median overall survival for all ICT-eligible patients was significantly longer for those ICT-treated patients than untreated patients (8.7 years vs. 4.7 years, log-rank p = 0.02; multivariate hazard ratio 0.372, p = 0.03). CONCLUSION: This study finds only 41% of ICT-eligible patients with lower-risk MDS received ICT in clinical practice, and treatment was initiated later than recommended. Receipt of ICT was associated with significantly longer survival.

Estimated effect of epoetin dosage on survival among elderly hemodialysis patients in the United States.

BACKGROUND AND OBJECTIVES: The common finding that low achieved hemoglobin in observational studies and high target hemoglobin in randomized trials each were associated with increased mortality and high epoetin dosage has suggested the possibility that high epoetin dosage might explain the increased mortality risk. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We considered data from 18,454 patients who were >or=65 yr, were in the US Renal Data System, started hemodialysis in 2003, and survived 3 mo on dialysis. We estimated the association between cumulative average epoetin dosage and survival through the subsequent 9 mo by using inverse probability weighting to adjust for time-dependent confounding by indication. RESULTS: Survival was similar throughout the entire follow-up period for the three hypothetical treatment regimens selected: Low dosage 15,000 U/wk, medium dosage 30,000 U/wk, and high dosage 45,000 U/wk. Compared with a cumulative average dosage of 20,000 to 30,000 U/wk, the estimated hazard ratio (HR; 95% confidence interval [CI]) was 0.90 (0.52 to 1.54) for <10,000, 0.84 (0.67 to 1.05) for 10,000 to <20,000 U/wk, 0.96 (0.76 to 1.21) for 20,000 to <40,000 U/wk, and 0.91 (0.67 to 1.22) for >40,000 U/wk. In contrast, conventional unweighted models, which do not adequately adjust for time-dependent confounding by indication, indicated an association between high cumulative average epoetin dosage and increased mortality. CONCLUSIONS: Our findings suggest that, on average, epoetin dosages >30,000 U/wk do not confer additional harm or benefit in elderly hemodialysis patients.

Iron supplementation for reducing morbidity and mortality in children with HIV.

BACKGROUND: The most prevalent haematologic disturbance associated with HIV in children (apart from CD4 lymphocytopenia) is anaemia. Anaemia associated with HIV arises from multiple mechanisms, including the direct inhibitory effect of HIV on red cell precursors, other locally prevalent and/or opportunistic infections, micronutrient deficiency, anaemia of chronic disease, and as a consequence of medicines given for HIV and/or other concurrent illnesses. Iron deficiency is the most common cause of nutritional anaemia globally. There is significant geographical overlap of areas of the world where iron deficiency anaemia (IDA) and paediatric HIV are distributed. Given the high prevalence of IDA, it is likely that many HIV-infected children also are iron deficient. The contribution of iron deficiency to anaemia in HIV-infected children has been described but is incompletely understood. Currently, iron supplementation for anaemic infants and children is routinely practiced without any obvious effect in most developing countries, which bear most of the burden of global paediatric HIV infections.Because iron deficiency and IDA are common in HIV-infected children in high-prevalence areas and because there are concerns about possible deleterious effects of iron, this review aims to assess the evidence for iron supplementation for reducing morbidity and mortality in HIV-infected children. OBJECTIVES: To determine whether iron supplementation improves clinical, immunologic, and virologic outcomes in children infected with HIV SEARCH STRATEGY: We used the comprehensive search strategy developed specifically by the Cochrane HIV/AIDS Review Group to identify HIV/AIDS randomised controlled trials, and searched the following electronic databases: MEDLINE (searched November 2007); Embase (searched December 2007); and CENTRAL (December 2007). This search was supplemented with a search of AIDSearch (searched December 2007) and NLM Gateway (searched December 2007) to identify relevant conference abstracts, as well as a search of the reference lists of all eligible articles. The search was not limited by language or publication status. SELECTION CRITERIA: Randomised controlled trials (RCTs) of iron supplementation in any form and dose in HIV-infected children aged 12 years and younger. DATA COLLECTION AND ANALYSIS: We independently screened the results of the search to select potentially relevant studies and to retrieve the full articles. We independently applied the inclusion criteria to the potentially relevant studies. No studies were identified that fulfilled the selection criteria. MAIN RESULTS: No RCTs of iron supplementation in HIV-infected children were found. IMPLICATIONS FOR CLINICAL PRACTICE: The current clinical practice of iron supplementation in HIV-infected children is based on weak evidence comprising observational studies and expert opinions. IMPLICATIONS FOR RESEARCH: High-quality RCTs of iron supplementation are urgently required, especially in areas with significant overlap of high prevalence of HIV, iron deficiency anaemia, and malaria. Policy makers should prioritise funding for these trials.

Effect of iron or multiple micronutrient supplements on the prevalence of anaemia among anaemic young children of a malaria-endemic area: a randomized double-blind trial.

OBJECTIVE: To assess the effect of supplementation with iron or multiple micronutrients (MM) on the prevalence of anaemia in a malaria-endemic area. METHODS: A community-based randomized double-blind trial was conducted in rural Burkina Faso, including children aged 6-23 months with haemoglobin (Hb) concentrations of 70-109 g/l who were randomized into an iron group (Fe, n = 96), an iron and zinc group (IZ, n = 100) or an MM group (MM, n = 100), 5 days/week for 6 months. All children were provided with insecticide-treated bednets; those who had a Plasmodium falciparum (PF) positive-smear at baseline and/or at each monthly checking received antimalarial therapy. RESULTS: The mean (SD) endpoint Hb concentration was higher in the MM group [113.2 (13.6) g/l] than in the IZ group [106.3 (15.6) g/l] and the Fe group [107.1 (12.9) g/l] (P = 0.001). Children in the MM group were more likely to recover from anaemia than those in the Fe group [prevalence rate ratios, PRR (95% confidence interval, CI) = 1.62 (1.22-2.15), P < 0.001]. The IZ group did not differ from the Fe group [PRR (95% CI) = 0.94 (0.65-1.35), P = 0.72]. None of the interactions on the effect of supplementation of baseline age (0.13), or baseline height-for-age z-score (P = 0.33), or incident PF parasitemia (P = 0.99), was significant. CONCLUSION: In this malaria-endemic area, in combination with malaria management, the MM supplement was more efficacious than the Fe supplement and the IZ supplement for reducing anaemia. Further investigation into limiting factors and amounts of micronutrients that would be more efficacious for reducing anaemia is recommended.

The fascinating but deceptive ferritin: to measure it or not to measure it in chronic kidney disease?

Although the emergence of erythropoiesis-stimulating agents has revolutionized the anemia management of chronic kidney disease (CKD) in the past two decades, strategies to assess iron (Fe) status and to provide Fe supplementation have remained indistinct. The reported cases of hemochromatosis in dialysis patients from the pre-erythropoiesis-stimulating agent era along with the possible associations of Fe with infection and oxidative stress have fueled the "iron apprehension." To date, no reliable marker of Fe stores in CKD has been agreed on. Serum ferritin continues to be the focus of attention. Almost half of all maintenance hemodialysis patients have a serum ferritin >500 ng/ml. In this ferritin range, Fe supplementation currently is not encouraged, although most reported hemochromatosis cases had a serum ferritin >2000 ng/ml. The moderate-range hyperferritinemia (500 to 2000 ng/ml) seems to be due mostly to non-Fe-related conditions, including inflammation, malnutrition, liver disease, infection, and malignancy. Recent epidemiologic studies have shown that a low, rather than a high, serum Fe is associated with a poor survival in maintenance hemodialysis patients. In multivariate adjusted models that mitigate the confounding effect of malnutrition-inflammation, serum ferritin <1200 ng/ml and Fe saturation ratio in 30 to 50% range are associated with the greatest survival in maintenance hemodialysis patients. Although ferritin is a fascinating molecule, moderate hyperferritinemia is a misleading marker of Fe stores in patients with CKD. It may be time to revisit the utility of serum ferritin in CKD and ask ourselves whether its measurement has helped us or has caused more confusion and controversy.

Iron deficiency in outdoor pig production.

It has been claimed that outdoor-reared suckling piglets do not need iron supplementation. According to practical experience, outdoor-reared and non-iron-supplemented piglets show a lower performance in comparison with their iron-supplemented counterparts. The purpose of the present study was to determine the effect of iron supplementation on outdoor-reared suckling piglets. In a large Hungarian outdoor pig production unit, 4691 piglets were assigned to one of two treatment groups. Piglets in group 1 (n = 2344): received no iron supplementation, whereas piglets in group 2 (n = 2347) were intramuscularly injected in the neck on day 3 post-partum with 1.5 ml of Ferriphor 10% solution (TAD Pharmaceutical GmbH, Bremerhaven, Germany). Animal weights, morbidity, haemoglobin concentration and mortality were recorded and analysed. At weaning the iron-injected piglets were significantly (P < 0.05) heavier. The iron-supplemented piglets also revealed significantly (P < 0.01) less pre-weaning morbidity and mortality and higher (P < 0.01) blood haemoglobin concentration compared with the non-injected ones. This study suggests that in order to prevent pre-weaning losses and support piglet health and weight performance, iron supplementation should be administered to piglets in outdoor pig production units.

Intermittent treatment for malaria and anaemia control at time of routine vaccinations in Tanzanian infants: a randomised, placebo-controlled trial.

BACKGROUND: Clinical malaria and severe anaemia are major causes of paediatric hospital admission and death in many malaria-endemic settings. In the absence of an effective and affordable vaccine, control programmes continue to rely on case management while attempting the large-scale deployment of insecticide-treated nets. We did a randomised, placebo-controlled trial to assess the efficacy and safety of intermittent sulphadoxine-pyrimethamine treatment on the rate of malaria and severe anaemia in infants in a rural area of Tanzania. METHODS: We randomly assigned 701 children living in Ifakara, southern Tanzania, sulphadoxine-pyrimethamine or placebo at 2, 3, and 9 months of age. All children received iron supplementation between 2 and 6 months of age. The intervention was given alongside routine vaccinations delivered through WHO's Expanded Program on Immunisation (EPI). The primary outcome measures were first or only episode of clinical malaria, and severe anaemia in the period from recruitment to 1 year of age. Morbidity monitoring through a hospital-based passive case-detection system was complemented by cross-sectional surveys at 12 and 18 months of age. Results were expressed in terms of protective efficacy (100 [1-hazard ratio]%) and analysis was by intention to treat. FINDINGS: 40 children dropped out (16 died, 11 migrated, 12 parents withdrew consent, and one for other reasons). Intermittent sulphadoxine-pyrimethamine treatment was well tolerated and no drug-attributable adverse events were recorded. During the first year of life, the rate of clinical malaria (events per person-year at risk) was 0.15 in the sulphadoxine-pyrimethamine group versus 0.36 in the placebo group (protective efficacy 59% [95% CI 41-72]), and the rate of severe anaemia was 0.06 in the sulphadoxine-pyrimethamine group versus 0.11 in the placebo group (50% [8-73]). Serological responses to EPI vaccines were not affected by the intervention. INTERPRETATION: This new approach to malaria control reduced the rate of clinical malaria and severe anaemia by delivering an available and affordable drug through the existing EPI system. Data are urgently needed to assess the potential cost-effectiveness of intermittent treatment in areas with different patterns of malaria endemicity.

Nutrition and maternal mortality in the developing world.

This review relates nutritional status to pregnancy-related death in the developing world, where maternal mortality rates are typically >/=100-fold higher than rates in the industrialized countries. For 3 of the central causes of maternal mortality (ie, induced abortion, puerperal infection, and pregnancy-induced hypertension), knowledge of the contribution of nutrition is too scanty for programmatic application. Hemorrhage (including, for this discussion, anemia) and obstructed labor are different. The risk of death is greatly increased with severe anemia (Hb <70 or 80 g/L); there is little evidence of increased risk associated with mild or moderate anemia. Current programs of universal iron supplementation are unlikely to have much effect on severe anemia. There is an urgent need to reassess how to approach anemia control in pregnant women. Obstructed labor is far more common in short women. Unfortunately, nutritional strategies for increasing adult stature are nearly nonexistent: supplemental feeding appears to have little benefit after 3 y of age and could possibly be harmful at later ages, inducing accelerated growth before puberty, earlier menarche (and possible earlier marriage), and unchanged adult stature. Deprived girls without intervention typically have late menarche, extended periods of growth, and can achieve nearly complete catch-up growth. The need for operative delivery also increases with increased fetal size. Supplementary feeding could therefore increase the risk of obstructed labor. In the absence of accessible obstetric services, primiparous women <1.5 m in height should be excluded from supplementary feeding programs aimed at accelerating fetal growth. The knowledge base to model the risks and benefits of increased fetal size does not exist.