Iron distribution in different tissues of homozygous Mask (msk/msk) mice and the effects of oral iron treatments.

Iron-refractory iron deficiency anemia (IRIDA) is an autosomal recessive disorder caused by genetic mutations on TMPRSS6 gene which encodes Matriptase2 (MT2). An altered MT2 cannot appropriately suppress hepatic BMP6/SMAD signaling in case of low iron, hence hepcidin excess blocks dietary iron absorption, leading to a form of anemia resistant to oral iron supplementation. In this study, using the IRIDA mouse model Mask, we characterized homozygous (msk/msk) compared to asymptomatic heterozygous (msk/wt) mice, assessing the major parameters of iron status in different organs, at different ages in both sexes. The effect of carbonyl iron diet was analyzed as control iron supplementation being used for many studies in mice. It resulted effective in both anemic control and msk/msk mice, as expected, even if there is no information about its mechanism of absorption. Then, we mainly compared two forms of oral iron supplement, largely used for humans: ferrous sulfate and Sucrosomial iron. In anemic control mice, the two oral formulations corrected hemoglobin levels from 11.40 ± 0.60 to 15.38 ± 1.71 g/dl in 2-4 weeks. Interestingly, in msk/msk mice, ferrous sulfate did not increase hemoglobin likely due to ferroportin/hepcidin-dependent absorption, whereas Sucrosomial iron increased it from 11.50 ± 0.60 to 13.53 ± 0.64 g/dl mainly in the first week followed by a minor increase at 4 weeks with a stable level of 13.30 ± 0.80 g/dl, probably because of alternative absorption. Thus, Sucrosomial iron, already used in other conditions of iron deficiency, may represent a promising option for oral iron supplementation in IRIDA patients.

New-onset restless leg syndrome in a COVID-19 patient: a case report with literature review.

Restless leg syndrome (RLS) is a sleep disorder characterized by the sudden urge to move the lower limbs during periods of rest accompanied by an unpleasant sensation like tingling or burning in the legs. Often, this urge is partially relieved by the movement of legs. However, it causes disturbance of sleep leading to daytime fatigue. Herein, we present an unusual case of new-onset of restless leg syndrome in a COVID-19 infected patient who presented three weeks after an uncomplicated delivery via caesarean section. The patient was managed with sleep hygiene measures, oral iron and vitamin C tablets apart from general COVID-19 management medications, subsequently leading to significant improvements. Here we have discussed possible associated factors, pathophysiological mechanisms and management of RLS in the case of COVID infected individuals.

Dietary iron overload mitigates atherosclerosis in high-fat diet-fed apolipoprotein E knockout mice: Role of dysregulated hepatic fatty acid metabolism.

The atherosclerosis "iron hypothesis" generates a fair amount of debate since it has been proposed. Here, we revisited the "iron hypothesis" by examining whether dietary iron overload would intensify iron deposition in plaques and thus lead to further exacerbation of atherosclerosis in apolipoprotein E knockout (ApoE KO) mice. ApoE KO mice were fed either a normal chow diet (ND) or a high fat diet (HFD) supplemented with or without 2% carbonyl iron (Fe) for 16 weeks. However, contrary to our assumption, dietary iron overloading did not intensify, but rather diminished the atherosclerotic lesion area by 65.3%, which was accompanied by significantly decreased serum total cholesterol, triglyceride and low-density lipoprotein cholesterol contents, together with hepatic lipid accumulation decline, despite the evident existence of aortic iron accumulation and the typical signs of iron overload in ApoE KO mice. Using isobaric tag for absolute quantification (iTRAQ) proteomics approach, hepatic CD36 and fatty acid binding proteins-mediated fatty acid (FA) uptake and trafficking impairment were identified as the key potential pathomechanisms by which iron overload diminishes atherosclerotic lesions. Furthermore, downstream hepatic FA de novo biosynthesis was enhanced and FA oxidation was inhibited to compensate for the FA deficiency triggered by iron overload-impaired fatty acid uptake and trafficking. Our findings suggested that dietary iron overload is not atherogenic in ApoE KO mice, and more research efforts are warranted to revisit the "iron hypothesis" of atherosclerosis.

Using Reticulocyte Hemoglobin Equivalent as a Marker for Iron Deficiency and Responsiveness to Iron Therapy.

OBJECTIVE: To assess the accuracy of a simplified approach for the diagnosis of iron deficiency anemia (IDA) based on the complete blood cell count (CBC) and reticulocyte analysis. PATIENTS AND METHODS: Five hundred fifty-six consecutive, nonselected patients referred for diagnosis and/or treatment of anemia were included in this diagnostic study to compare the performance of reticulocyte hemoglobin equivalent (RET-He) versus traditional biochemical markers for diagnosis and treatment of IDA. Complete blood count, serum ferritin, iron, and transferrin saturation were performed as clinically indicated. Reticulocyte hemoglobin equivalent was measured with a Sysmex XN-450 analyzer on the residual CBC sample. The study period was from September 20, 2017, through and including November 15, 2018. RESULTS: Patients (N=556) were studied at baseline, of whom 150 were subsequently treated with intravenous iron. Receiver operating characteristic analysis yielded an RET-He cut-off of 30.7 pg to identify IDA (area under curve, 0.733; 95% CI, 0.692 to 0.775), with 68.2% sensitivity and 69.7% specificity. Patients (n=240) were seen at follow-up, with 57 treated and 183 not treated with intravenous iron. Responsiveness was defined as a hemoglobin increase of ≥1.0 g: a combination of RET-He <28.5 pg and hemoglobin value <10.3 g/dL had 84% sensitivity and 78% specificity as response predictor (area under the curve, 0.749; 95% CI, 0.622 to 0.875). CONCLUSION: Data from CBC and RET-He can identify patients with IDA, determine need for and responsiveness to intravenous iron, and reduce time for therapeutic decisions. Limitations of this study are uncontrolled design, its single-site and retrospective nature, and that it requires prospective validation.

Newer formulations of intravenous iron: a review of their chemistry and key safety aspects - hypersensitivity, hypophosphatemia, and cardiovascular safety.

Introduction: The newest intravenous (IV) iron products show an improved safety profile over predecessors, allowing for the rapid administration of relatively high doses. Ferric derisomaltose (FDI; also known as iron isomaltoside), ferric carboxymaltose (FCM), and ferumoxytol (FER), are successful treatments for iron deficiency (Europe; FDI and FCM) and iron deficiency anemia (US; FDI, FCM, and FER).Areas covered: This review focusses on the chemistry and structure of FDI, FCM, and FER, and on three key aspects of IV iron safety: (1) hypersensitivity; (2) hypophosphatemia and sequelae; (3) cardiovascular safety.Expert opinion: Although the safety of modern IV iron has improved, immediate infusion reactions and the development of hypophosphatemia must be appreciated and recognized by those who prescribe and administer IV iron. Immediate infusion reactions can occur with any IV iron and are usually mild; severe reactions - particularly anaphylaxis - are extremely rare. The recognition and appropriate management of infusion reactions is an important consideration to the successful administration of IV iron. Severe, persistent, hypophosphatemia is a specific side effect of FCM. No cardiovascular safety signal has been identified for IV iron. Ongoing trials in heart failure will provide additional long-term efficacy and safety data.

Effect of mass deworming with antihelminthics for soil-transmitted helminths during pregnancy.

BACKGROUND: Helminthiasis is an infestation of the human body with parasitic worms. It is estimated to affect 44 million pregnancies, globally, each year. Intestinal helminthiasis (hookworm infestation) is associated with blood loss and decreased supply of nutrients for erythropoiesis, resulting in iron-deficiency anaemia. Over 50% of the pregnant women in low- and middle-income countries (LMIC) suffer from iron-deficiency anaemia. Though iron-deficiency anaemia is multifactorial, hookworm infestation is a major contributory cause in women of reproductive age in endemic areas. Antihelminthics are highly efficacious, but evidence of their beneficial effect and safety when given during pregnancy has not been established. This is an update of a Cochrane Review last published in 2015. OBJECTIVES: To determine the effects of mass deworming with antihelminthics for soil-transmitted helminths (STH) during the second or third trimester of pregnancy on maternal and pregnancy outcomes. SEARCH METHODS: For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP) (8 March 2021) and reference lists of retrieved studies. SELECTION CRITERIA: We included all prospective randomised controlled trials evaluating the effect of administration of antihelminthics versus placebo or no treatment during the second or third trimester of pregnancy; both individual-randomised and cluster-randomised trials were eligible. We excluded quasi-randomised trials and studies that were only available as abstracts with insufficient information. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data, checked accuracy and assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included a total of six trials (24 reports) that randomised 7873 pregnant women. All of the included trials were conducted in antenatal clinics within hospitals in LMICs (Uganda, Nigeria, Peru, India, Sierra Leone and Tanzania). Among primary outcomes, five trials reported maternal anaemia, one trial reported preterm birth and three trials reported perinatal mortality. Among secondary outcomes, included trials reported maternal worm prevalence, low birthweight (LBW) and birthweight. None of the included studies reported maternal anthropometric measures or infant survival at six months. Overall, we judged the included trials to be generally at low risk of bias for most domains, while the certainty of evidence ranged from low to moderate. Analysis suggests that administration of a single dose of antihelminthics in the second trimester of pregnancy may reduce maternal anaemia by 15% (average risk ratio (RR) 0.85, 95% confidence interval (CI) 0.72 to 1.00; I²= 86%; 5 trials, 5745 participants; low-certainty evidence). We are uncertain of the effect of antihelminthics during pregnancy on preterm birth (RR 0.84, 95% CI 0.38 to 1.86; 1 trial, 1042 participants; low-certainty evidence) or perinatal mortality (RR 1.01, 95% CI 0.67 to 1.52; 3 trials, 3356 participants; low-certainty evidence). We are uncertain of the effect of antihelminthics during pregnancy on hookworm (average RR 0.31, 95% CI 0.05 to 1.93; Tau² = 1.76, I² = 99%; 2 trials, 2488 participants; low-certainty evidence). Among other secondary outcomes, findings suggest that administration of antihelminthics during pregnancy may reduce the prevalence of trichuris (average RR 0.68, 95% CI 0.48 to 0.98; I²=75%; 2 trials, 2488 participants; low-certainty evidence) and ascaris (RR 0.24, 95% CI 0.19 to 0.29; I²= 0%; 2 trials, 2488 participants; moderate-certainty evidence). Antihelminthics during pregnancy probably make little or no difference to LBW (RR 0.89, 95% CI 0.69 to 1.16; 3 trials, 2960 participants; moderate-certainty evidence) and birthweight (mean difference 0.00 kg, 95% CI -0.03 kg to 0.04 kg; 3 trials, 2960 participants; moderate-certainty evidence). AUTHORS' CONCLUSIONS: The evidence suggests that administration of a single dose of antihelminthics in the second trimester of pregnancy may reduce maternal anaemia and worm prevalence when used in settings with high prevalence of maternal helminthiasis. Further data is needed to establish the benefit of antihelminthic treatment on other maternal and pregnancy outcomes. Future research should focus on evaluating the effect of these antihelminthics among various subgroups in order to assess whether the effect varies. Future studies could also assess the effectiveness of co-interventions and health education along with antihelminthics for maternal and pregnancy outcomes.

Efficacy of a 28-compartment pillbox for improving iron supplement compliance in healthy pregnant women: a randomised controlled trial.

A randomised controlled trial was conducted. The primary objective was to evaluate the efficacy of a pillbox for increasing iron supplement compliance by comparing the proportion of pregnant women who had no remaining iron tablets between pregnant women attending ANC who were given a pillbox to use and women with no pillbox in four-week period between ANC visits. The secondary objective was to evaluate the reasons for poor compliance and possible factors associated with the non-compliance. One hundred and ninety pregnant women were enrolled, 95 participants were randomised into each of the groups. The proportion of pregnant women who had no remaining iron tablets at the end was statistically significantly lower in the pillbox group than in the control group [53.3% and 23.1%, respectively, p < .001, RR2.308 (95% CI 1.515 - 3.517)]. The most common reason given for having of iron tablets remaining was forgetfulness. The visual analog scale (VAS) scores indicated that patient's responsibility feeling, duration of sleep each day and presence of a handicapped or small child in care significantly influenced the proportion of pregnant women who had remaining iron tablets at the end in both groups. We concluded that a pillbox was found to be an effective tool for improving pregnant women's compliance with taking their iron supplements.IMPACT STATEMENTWhat is already known about this subject? Antenatal care (ANC) influences maternal and neonatal outcomes. The incidence of anaemia in pregnant women is reported to be around 42% and approximately 50% result from iron deficiency. Maternal anaemia increases the risk of foetal low birth weight, preterm birth, perinatal mortality, stillbirth and maternal mortality.What do the results of this study add? The 28-compartment pillbox is effective for improving iron supplement compliance in healthy pregnant women. Forgetfulness is the most common reason given for having remaining iron tablets. The lower score on the visual analog scale of patient's feeling of responsibility, long duration of sleep a day and the presence of a handicapped or small child in their care were significantly associated with having remaining iron tablets.What are the implications are of these finding for clinical practice and/or further research? The 28-compartment pillbox can be implied to routine antenatal care for improving iron supplement compliance in healthy pregnant women. Health care providers should be reminded to encourage compliance with iron supplement prescription in pregnant women who are at risk of poor compliance as indicated by low VAS of the patient's feeling of responsibility, long duration of sleep in a day and pregnant women who have responsibility to take care of handicapped or small children.

Iron Fortification Practices and Implications for Iron Addition to Salt.

This introductory article provides an in-depth technical background for iron fortification, and thus introduces a series of articles in this supplement designed to present the current evidence on the fortification of salt with both iodine and iron, that is, double-fortified salt (DFS). This article reviews our current knowledge of the causes and consequences of iron deficiency and anemia and then, with the aim of assisting the comparison between DFS and other common iron-fortified staple foods, discusses the factors influencing the efficacy of iron-fortified foods. This includes the dietary and physiological factors influencing iron absorption; the choice of an iron compound and the fortification technology that will ensure the necessary iron absorption with no sensory changes; encapsulation of iron fortification compounds to prevent unacceptable sensory changes; the addition of iron absorption enhancers; the estimation of the iron fortification level for each vehicle based on iron requirements and consumption patterns; and the iron status biomarkers that are needed to demonstrate improved iron status in populations regularly consuming the iron-fortified food. The supplement is designed to provide a summary of evidence to date that can help advise policy makers considering DFS as an intervention to address the difficult public health issue of iron deficiency anemia, while at the same time using DFS to target iodine deficiency.

Interventions for treating iron deficiency anaemia in inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease affects approximately seven million people globally. Iron deficiency anaemia can occur as a common systemic manifestation, with a prevalence of up to 90%, which can significantly affect quality of life, both during periods of active disease or in remission. It is important that iron deficiency anaemia is treated effectively and not be assumed to be a normal finding of inflammatory bowel disease. The various routes of iron administration, doses and preparations present varying advantages and disadvantages, and a significant proportion of people experience adverse effects with current therapies. Currently, no consensus has been reached amongst physicians as to which treatment path is most beneficial. OBJECTIVES: The primary objective was to evaluate the efficacy and safety of the interventions for the treatment of iron deficiency anaemia in people with inflammatory bowel disease. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and two other databases on 21st November 2019. We also contacted experts in the field and searched references of trials for any additional trials. SELECTION CRITERIA: Randomised controlled trials investigating the effectiveness and safety of iron administration interventions compared to other iron administration interventions or placebo in the treatment of iron deficiency anaemia in inflammatory bowel disease. We considered both adults and children, with studies reporting outcomes of clinical, endoscopic, histologic or surgical remission as defined by study authors. DATA COLLECTION AND ANALYSIS: Two review authors independently conducted data extraction and 'Risk of bias' assessment of included studies. We expressed dichotomous and continuous outcomes as risk ratios and mean differences with 95% confidence intervals. We assessed the certainty of the evidence using the GRADE methodology. MAIN RESULTS: We included 11 studies (1670 randomised participants) that met the inclusion criteria. The studies compared intravenous iron sucrose vs oral iron sulphate (2 studies); oral iron sulphate vs oral iron hydroxide polymaltose complex (1 study); oral iron fumarate vs intravenous iron sucrose (1 study); intravenous ferric carboxymaltose vs intravenous iron sucrose (1 study); erythropoietin injection + intravenous iron sucrose vs intravenous iron sucrose + injection placebo (1 study); oral ferric maltol vs oral placebo (1 study); oral ferric maltol vs intravenous ferric carboxymaltose (1 study); intravenous ferric carboxymaltose vs oral iron sulphate (1 study); intravenous iron isomaltoside vs oral iron sulphate (1 study); erythropoietin injection vs oral placebo (1 study). All studies compared participants with CD and UC together, as well as considering a range of disease activity states. The primary outcome of number of responders, when defined, was stated to be an increase in haemoglobin of 20 g/L in all but two studies in which an increase in 10g/L was used. In one study comparing intravenous ferric carboxymaltose and intravenous iron sucrose, moderate-certainty evidence was found that intravenous ferric carboxymaltose was probably superior to intravenous iron sucrose, although there were responders in both groups (150/244 versus 118/239, RR 1.25, 95% CI 1.06 to 1.46, number needed to treat for an additional beneficial outcome (NNTB) = 9). In one study comparing oral ferric maltol to placebo, there was low-certainty evidence of superiority of the iron (36/64 versus 0/64, RR 73.00, 95% CI 4.58 to 1164.36). There were no other direct comparisons that found any difference in the primary outcomes, although certainty was low and very low for all outcomes, due to imprecision from sparse data and risk of bias varying between moderate and high risk. The reporting of secondary outcomes was inconsistent. The most common was the occurrence of serious adverse events or those requiring withdrawal of therapy. In no comparisons was there a difference seen between any of the intervention agents being studied, although the certainty was very low for all comparisons made, due to risk of bias and significant imprecision due to the low numbers of events. Time to remission, histological and biochemical outcomes were sparsely reported in the studies. None of the other secondary outcomes were reported in any of the studies. An analysis of all intravenous iron preparations to all oral iron preparations showed that intravenous administration may lead to more responders (368/554 versus 205/373, RR 1.17, 95% CI 1.05 to 1.31, NNTB = 11, low-certainty due to risk of bias and inconsistency). Withdrawals due to adverse events may be greater in oral iron preparations vs intravenous (15/554 versus 31/373, RR 0.39, 95% CI 0.20 to 0.74, low-certainty due to risk of bias, inconsistency and imprecision). AUTHORS' CONCLUSIONS: Intravenous ferric carboxymaltose probably leads to more people having resolution of IDA (iron deficiency anaemia) than intravenous iron sucrose. Oral ferric maltol may lead to more people having resolution of IDA than placebo. We are unable to draw conclusions on which of the other treatments is most effective in IDA with IBD (inflammatory bowel disease) due to low numbers of studies in each comparison area and clinical heterogeneity within the studies. Therefore, there are no other conclusions regarding the treatments that can be made and certainty of all findings are low or very low. Overall, intravenous iron delivery probably leads to greater response in patients compared with oral iron, with a NNTB (number needed to treat) of 11. Whilst no serious adverse events were specifically elicited with any of the treatments studied, the numbers of reported events were low and the certainty of these findings very low for all comparisons, so no conclusions can be drawn. There may be more withdrawals due to such events when oral is compared with intravenous iron delivery. Other outcomes were poorly reported and once again no conclusions can be made as to the impact of IDA on any of these outcomes. Given the widespread use of many of these treatments in practice and the only guideline that exists recommending the use of intravenous iron in favour of oral iron, research to investigate this key issue is clearly needed. Considering the current ongoing trials identified in this review, these are more focussed on the impact in specific patient groups (young people) or on other symptoms (such as fatigue). Therefore, there is a need for studies to be performed to fill this evidence gap.

Questions and answers on iron deficiency treatment selection and the use of intravenous iron in routine clinical practice.

Iron deficiency is a common cause of morbidity and can arise as a consequence or complication from many diseases. The use of intravenous iron has increased significantly in the last decade, but concerns remain about indications and administration. Modern intravenous iron preparations can facilitate rapid iron repletion in one or two doses, both for absolute iron deficiency and, in the presence of inflammation, functional iron deficiency, where oral iron therapy is ineffective or has not worked. A multidisciplinary team of experts experienced in iron deficiency undertook a consensus review to support healthcare professionals with practical advice on managing iron deficiency in gastrointestinal, renal and cardiac disease, as well as; pregnancy, heavy menstrual bleeding, and surgery. We explain how intravenous iron may work where oral iron has not. We provide context on how and when intravenous iron should be administered, and informed opinion on potential benefits balanced with potential side-effects. We propose how intravenous iron side-effects can be anticipated in terms of what they may be and when they may occur. The aim of this consensus is to provide a practical basis for educating and preparing staff and patients on when and how iron infusions can be administered safely and efficiently. Key messages Iron deficiency treatment selection is driven by several factors, including the presence of inflammation, the time available for iron replenishment, and the anticipated risk of side-effects or intolerance. Intravenous iron preparations are indicated for the treatment of iron deficiency when oral preparations are ineffective or cannot be used, and therefore have applicability in a wide range of clinical contexts, including chronic inflammatory conditions, perioperative settings, and disorders associated with chronic blood loss. Adverse events occurring with intravenous iron can be anticipated according to when they typically occur, which provides a basis for educating and preparing staff and patients on how iron infusions can be administered safely and efficiently.

Association of erythropoietin resistance and fibroblast growth factor 23 in dialysis patients: Results from the Japanese Dialysis Outcomes and Practice Patterns Study.

BACKGROUND: Fibroblast growth factor 23 (FGF23) plays an important role in chronic kidney disease (CKD)-related mineral and bone disorders. High FGF23 levels are associated with increased risk of anaemia in non-haemodialysis CKD patients. FGF23 also negatively regulates erythropoiesis in mice. We hypothesized that higher FGF23 levels are associated with increased erythropoietin hyporesponsiveness among haemodialysis patients. METHODS: The study included 1044 patients from the Japanese Dialysis Outcomes and Practice Patterns Study (J-DOPPS) phase 5 (2012-2015). The outcome was erythropoiesis-stimulating agent hyporesponsiveness (ESA-hypo), defined as mean Hgb <10 g/dL and standardized mean ESA dose >6000 u/week over 4 months following FGF23 measurement. The association between ESA-hypo and FGF23 was estimated using multivariable-adjusted logistic generalized estimating equation regression models. RESULTS: Patients with higher levels of FGF23 were younger and had higher levels of serum albumin, creatinine, albumin-corrected calcium, phosphorus, PTH, 25(OH)-vitamin D, and had higher percentages of intravenous (IV) iron, IV vitamin D and cinacalcet use. ESA-hypo was present in 144 patients (13.8%). Compared with the third quintile of FGF23 levels, the odds ratio (95% CI) of ESA-hypo was 2.14 (0.99, 4.62) and 1.74 (0.74, 4.11) for the first and fifth quintiles, respectively. CONCLUSION: The lowest and highest levels of FGF23 were associated with higher odds of ESA-hypo in patients on maintenance haemodialysis, although the associations were not statistically significant. The relationship between FGF23 and anaemia, and particularly the increased risks of ESA-hypo at low FGF23 levels which might be the result of energy saving, must be confirmed in larger clinical studies.

Improving the safety of intravenous iron treatments for patients with chronic kidney disease.

Introduction: Iron-deficiency anemia in chronic kidney disease (CKD) is common and has prognostic, financial, and quality of life implications. Intravenous (IV) iron is a key intervention for optimal management, however, ongoing safety concerns exist. Area covered: The potential side effects associated with IV iron use are addressed as we review the most recent studies. Hypersensitivity reactions and true anaphylaxis are indeed rare with a greater understanding of the nature of labile iron and 'Fishbane' reactions. Hypophosphatemia appears commoner with certain IV iron preparations, however its significance in CKD requires exploration. The long-standing questions regarding oxidative stress and the potential susceptibility to infections and worsening cardiovascular morbidity are discussed. Iron overload secondary to repeat IV iron infusions is plausible, however, a number of guidelines limit and strictly guide prescription. Expert opinion: The past decade has improved our understanding of IV iron administration safety in patients with CKD. Third generation IV iron compounds have minimized hypersensitivity reactions while allowing high doses to be administered safely and rapidly in non-dialysis-dependent CKD patients. However, differences in safety profiles such as hypophosphatemia require further study and therapy should be tailored to the individual. Clinicians should feel confident in using IV iron therapy.

Relationship between patient ethnicity and prevalence of anemia during pregnancy and the puerperium period and compliance with healthcare recommendations - implications for targeted health policy.

BACKGROUND: Anemia is common during pregnancy and the puerperium. The association of ethnicity as well as other characteristics with anemia and compliance with healthcare recommendations has not been studied sufficiently and needs to be explored in order to implement a targeted health policy. We examined the association between ethnicity and the risk for prenatal and puerperium anemia and the compliance with healthcare recommendations. This effort aims to guide reforms in policies and practices that will assist in decreasing anemia prevalence in Israel. METHODS: This study was a secondary analysis of a prospective cohort study database including 1558 women who delivered vaginally at Emek Medical Center. Anemia was assessed before delivery by obtaining a complete blood count (CBC). After delivery, CBCs were taken in cases of postpartum hemorrhage, symptoms consistent with anemia, prenatal anemia or other clinical indications. The study population was divided according to their ethnicity (Jews and Arabs). The primary outcomes were anemia before delivery, anemia in the immediate postpartum and 6 weeks postpartum, and compliance with healthcare recommendations, which was defined as the rate of women who performed a routine CBC test 6-weeks-postpartum. RESULTS: The rates of anemia before delivery and in the puerperium period were similar between Jews and Arabs (before delivery: 88 (11%) versus 98 (14%); 6 weeks postpartum: 55 (21%) vs 68 (28%), respectively;p > 0.05). Iron supplementation was high in both groups during pregnancy (~ 90%) and lower during the postpartum for Jews compared to Arabs (72% vs 83%,respectively; P < .0001). Only one third of the patients performed a CBC 6-weeks-postpartum regardless of ethnicity. CONCLUSION: Overall compliance with health recommendation was high during pregnancy but low postpartum and was reflected in anemia persistence regardless of ethnicity. Because of the adverse long term impact of anemia on patient's health, new policies need to be developed to improve patient's compliance postpartum. A possible strategy is to combine the follow-up of the mother with the one of the newborn in the family health stations (Tipat Halav) and the community clinics similarly to the close follow-up during pregnancy. Additional methods may include active summoning for CBC test and assuring iron supplement consumption.

[Moderate anaemia refractory to oral iron in a pregnant woman with a history of bariatric surgery]. / Anemia moderada refractaria al hierro oral en una gestante con antecedente de cirugía bariátrica.

INTRODUCTION: Introduction: bariatric surgery involves nutritional and trace element deficiencies that may have a negative impact if not treated properly, especially in situations such as pregnancy. Case report: a patient who underwent biliopancreatic diversion surgery without subsequent therapeutic adherence consults due to edema; findings included 29-week gestation (type 1 intrauterine growth restriction) and moderate anemia. Vitamin supplementation, oligoelements, enteral nutrition, and intravenous iron were restarted. Due to poor hemoglobin response with repleted iron deposits, recombinant human erythropoietin was associated. Discussion: the most frequent nutritional deficiencies after malabsorptive bariatric surgery are sideropenia and hypoproteinemia. Sideropenia and anemia increase the risk of preterm delivery, low weight, and perinatal mortality. In patients with inadequate response to intravenous iron, treatment with recombinant human erythropoietin may be considered, although its use in pregnant women without chronic renal failure has no indication in the prescribing information of this drug.

INTRODUCCIÓN: Introducción: la cirugía bariátrica (CB) implica déficits nutricionales y de oligoelementos que pueden tener una repercusión negativa en caso de no tratarse adecuadamente, especialmente en situaciones como la gestación. Caso clínico: paciente sometida a CB del tipo de la derivación biliopancreática, sin adherencia terapéutica posterior, que acude por edemas, confirmándose la presencia de una gestación de 29 semanas (feto CIR de tipo I) y de anemia moderada. Se reinició la suplementación de vitaminas, oligoelementos, nutrición enteral y hierro intravenoso (FEIV). Debido a la escasa respuesta de la hemoglobina con depósitos de hierro repletados, se asoció eritropoyetina humana recombinante (rHuEPO). Discusión: los déficits nutricionales más frecuentes tras una CB malabsortiva son la ferropenia y la hipoproteinemia. La ferropenia y la anemia incrementan el riesgo del parto pretérmino, el bajo peso y la mortalidad perinatal. En las pacientes sin adecuada respuesta al FEIV puede plantearse el tratamiento con rHuEPO, aunque su uso en gestantes sin insuficiencia renal crónica no dispone de indicación en la ficha técnica.

Managing preoperative anemia: Evolving concepts and strategies for improving patient outcomes.

Anemia is the most common hematological disease, and is defined by the World Health Organization as a condition in which the number of red blood cells and consequently oxygen-carrying capacity is insufficient to meet the physiological needs of the body. Anemia can occur throughout the perioperative period and has important clinical consequences. Preoperative anemia is usually regarded as no more than a surrogate marker of a patient's physical status, and it is not always adequately addressed before surgery. Postoperative anemia is a common event and occurs in 80-90% of patients who have undergone major surgery. This manuscript discusses the detection and management of preoperative anemia, the three pillars of patient blood management, perioperative anemia management, and risk stratification for anemia in the surgical setting.

Recovery of Iron Stores After Adolescents Donate Blood.

BACKGROUND: Teenagers aged 16 to 18 are at increased risk for iron deficiency, exacerbated by losses with whole blood (WB) or double red blood cell (2RBC) donations. Required 56-day (WB) or 112-day (2RBC) interdonation intervals (IDIs) are too short for many to replace lost iron without supplements. METHODS: Teenagers donating WB or 2RBCs at Vitalant, a national blood provider, had serum ferritin measured at their first and immediately subsequent successful donation from December 2016 to 2018. We modeled postindex log-ferritin as a function of IDI to estimate the shortest intervals that corresponded with 50% to 95% prevalence of adequate donor iron stores (ferritin ≥20 ng/mL female donors, ≥30 ng/mL male donors) at the subsequent donation. RESULTS: Among 30 806 teenagers, 11.4% of female and 9.7% of male donors had inadequate iron stores at index donation. Overall, 92.6% had follow-up ferritin values within 13 months. Approximately 12 months after WB index donations, >60% of female and >80% of male donors had adequate iron stores (>50% and >70% after 2RBC donations). Follow-up-donation iron stores were highly dependent on index ferritin. Less than half of WB donors with low ferritin at index achieved adequate stores within 12 months. Achieving a ≥90% prevalence of adequate ferritin at 12 months required index values >50 ng/mL. CONCLUSIONS: These findings suggest that postdonation low-dose iron supplements should be strongly encouraged in teenagers with borderline or low iron stores to permit donation without increased risk for symptoms of mild iron depletion. Increasing the minimum recommended IDI to allow time for replacing donation-related iron losses may be desirable for teenagers.

The Influence of Antenatal Oral Iron and Folic Acid Side Effects on Supplementation Duration in Low-Resource Rural Kenya: A Cross-Sectional Study.

BACKGROUND: Undesirable effects of a daily regimen of iron and folic acid ingested jointly (iron-folate) are potential disincentives to optimal antenatal supplementation. We intended to profile antenatal iron-folate side effects and elucidate their influence on supplementation duration in low-resource rural Kenya. METHODS: This was a cross-sectional descriptive study of randomly selected postnatal mothers of under-five-year-old children. Using a modified WHO Safe Motherhood Assessment standard questionnaire, they recalled the total number of days of antenatal iron-folate intake and the attendant supplement-attributed undesirable experiences. The analyses considered only participants who ingested the supplements in their immediate last pregnancies (n = 277). RESULTS: About half of the study participants reported at least a side effect and a mean of 2.4 (SD 1.5) effects per person in the entire pregnancy period. Most common reported effects were chest pains (31.8%), constipation (28.5%), severe stomach pains (11.6%), and diarrhoea (11.6%). Mothers who reported at least a side effect ingested the supplements for ten days less compared to those who did not experience any effect (p = 0.03); and a greater proportion of the former were primigravida (p = 0.02) and used combined form of iron and folic acid (p = 0.003). In a multivariate analysis, significant correlations with supplementation compliance (ingestion for 90+ days) were found only for nausea and severe stomach pain experiences (r = -0.1, p = 0.04; r = 0.2, p = 0.01, resp.). CONCLUSIONS: The commonness of undesirable experiences attributed to daily ingestion of 60 mg iron and 0.4 mg folic acid and their deterrence to longer supplementation durations suggest the need for considering a weekly intermittent regimen for some antenatal women in such set-ups. Our study demonstrated that potentially, more counselling on nausea as a side effect might be critical in advancing iron-folate supplementation compliance.

A randomized controlled trial comparing oral and intravenous iron supplementation after Roux-en-Y gastric bypass surgery.

BACKGROUND: Iron deficiency (ID) is one of the most common postoperative deficiencies that may develop after Roux-en-Y gastric bypass (RYGB). The optimal mode of treatment is uncertain. AIM: To compare the efficacy of oral ferrous fumarate (FF), oral ferrous gluconate (FG), and a single intravenous infusion of ferric carboxymaltose (FCM) in women with ID after RYGB. METHODS: Multicenter randomized controlled trial including 120 women with a serum ferritin <20 µg/l during follow-up after RYGB. They were randomized into three groups: 41 patients were treated with FF 200 mg three times a day (total daily dose: 195 mg elemental iron), 39 received FG 695 mg twice a day (total daily dose: 160 mg elemental iron) for three months, and 39 patients were treated with a single intravenous dose of FCM (1000 mg elemental iron). Serum ferritin levels were measured at six weeks, and three, six and twelve months after the start of supplementation. RESULTS: At three months, persistence of ID was observed in 29.4% and 42.4% of the patients treated with FF and FG, respectively, but in none of those treated with FCM (p < 0.001). Over the next nine months, recurrence of ID was observed in 56.5% of patients treated with FF, in 52.9% treated with FG, and in 27.8% of those treated with FCM. Adverse effects were most common during oral treatment. CONCLUSION: In women developing ID after RYGB, a single dose of intravenous FCM is more effective and better tolerated than the standard treatment with either FF or FG. CLINICAL TRIAL REGISTRY NUMBER AND WEBSITE: The study was registered at clinicaltrials.gov under number NCT02271997.