Iron Supplementation Research Articles

Iron deficiency and all-cause mortality after myocardial infarction

Abstract Introduction Iron deficiency (ID) is commonly associated with cardiovascular diseases, including myocardial infarction (MI). However, the data on the clinical significance of ID in patients with MI are conflicting. This may be related to the use of various ID criteria. Purpose Our study aimed to compare the association of different ID criteria with all-cause mortality after MI. Methods Consecutive patients hospitalized at a large tertiary heart center for type 1 MI without previous history of coronary artery disease were included. We evaluated the association of different iron metabolism parameters measured on the first day after hospital admission with all-cause mortality during the follow-up. Results Of a cohort of 1,156 patients included (aged 64±12 years, 25% women), 194 (16.8%) died during the median follow-up of 3.4 years (IQR 626-1782 days). A total of 51,7% of post-MI patients had low iron levels (≤13 µmol/L), and 16,3% of them had iron level ≤12.8 µmol/L and soluble transferrin receptor (sTfR) ≥3 mg/L. After multivariate adjustment, iron level ≤13 µmol/L (HR 1.67, 95% CI 1.19-2.34) and the combination of iron level ≤12.8 µmol/L and sTfR ≥3 mg/L (HR 2.56, 95% CI 1.64-3.99) were associated with an increased risk of mortality. This information provided additional predictive value to the GRACE score. No association between ferritin level and mortality was found. Compared to the model which contains iron level, the addition of sTfR improved risk stratification (net reclassification improvement 0.61, 95% CI 0.52-0.69) by reclassifying patients into a higher-risk group. Conclusion ID is common among patients with the first MI. The criteria based on iron and soluble transferrin receptor levels provide the best prediction of mortality, and should be evaluated in future interventional studies with intravenous iron therapy.Kaplan-Meier survival for iron levelsK-M survival for combined ID parameters

Drug-drug interactions of empagliflozin and dapagliflozin

Abstract Introduction The sodium glucose co-transporter2-inhibitors dapagliflozin (Dapa) and empagliflozin (Empa), initially developed as antihyperglycemic agents, are increasingly also prescribed for non-diabetic patients with heart failure (HF). Glucuronidation by uridine-diphosphate glucuronosyltransferase (UGT)1A9 is the main mechanism of metabolism of Dapa, whereas Empa is eliminated mainly by excretion. Both Dapa and Empa are substrates of P-glycoprotein. The risk for drug-drug interactions (DDI) of Empa and Dapa is assumed to be low. Aim of this study was to summarize reports of DDI of Empa and Dapa from the literature. Methods Search-terms in PubMed were "drug-drug interaction" and AND "sodium glucose co-transporter2-inhibitors" OR "SGLT2" OR "dapagliflozin" OR "empagliflozin". The drugs were classified according the Anatomical Therapeutic Chemical (ATC) system. Included were randomized trials, pharmacovigilance studies, case series, case reports, studies in healthy subjects and in vivo data. The funding of the study and the disclosures of the authors were registered. Results In 45 reports DDI of Empa and Dapa with 29 drugs were described (Table). According to the ATC system, these were drugs for the alimentary tract and metabolism (n=5), blood and blood forming organs (n=2), cardiovascular system (n=11), genitourinary system and sex hormones (n=2), antiinfectives (n=2), antineoplastic and immunomodulating agents (n=3), musculo-skeletal system (n=2) and nervous system (n=2). The reports comprised studies in healthy subjects (n=28), case reports (n=7), case series (n=6), pharmacovigilance studies (n=2), a subgroup analysis of a randomized trial (n=1) and in vivo data (n=1). Most of the reports found no clinically relevant DDI (n=32). Dapa and Empa both had a synergistic diuretic effect with bumetanide, and led to severe infections when combined with the interleukin-17-inhibitors secukinumab or ixekizumab. Empa administered with intravenous iron was reported to increase cell-iron availability, with lithium to reduce lithium exposure and with valproate to increase valproate exposure. Dapa administered with sacubitril-valsartan was reported to lead to severe hypotension, with linezolid to pancytopenia, with donafenib to an increased exposure to donafenib, with rifampicin to a reduction and mefenamic acid to an increase in Dapa exposure. Of the 45 reports, 33 were funded by a pharmaceutical company marketing Dapa or Empa and 33 had authors with conflicts of interest with pharmaceutical companies marketing Dapa or Empa. Conclusions Most data about DDI of Empa and Dapa derive from studies in healthy subjects and from the marketing companies. The clinical relevance DDI of Empa and Dapa in polymorbid patients with polymedication is largely unknown. There is an urgent need for independent studies on DDI of these drugs in diabetic and non-diabetic patients with HF.Table

The efficacy of IV iron in anemic heart failure patients: a systemic review and meta-analysis of randomised controlled trials

Abstract Introduction Iron deficiency in the context of heart failure is a multifaceted concern, where the intricate interplay between diminished iron stores, impaired absorption mechanisms, and reduced recycled iron in the reticuloendothelial system adds a layer of complexity to patient management. Initial attempts to address this issue with oral iron treatments have been questioned due to its poor absorption. Intravenous iron therapy is now preferred, as it has been shown to reduce heart failure hospitalisations and cardiovascular mortality. However, there is a lack of randomised studies specifically focused on heart failure patients, highlighting the need for more targeted investigations. Purpose The aim of this review is to provide reliable evidence from published randomised controlled trials (RCTs) regarding the beneficial effect of IV iron in heart failure patients. Methods We systematically searched PubMed, Web of Science, Scopus, and Cochrane Central, and EMBASE from inception until December 2023. We included randomised controlled trials (RCTs) comparing the effect of IV iron in heart failure patients versus placebo. The primary outcomes were 6MWT mean change, ferritin concentration mean change, transferrin saturation mean change and worsening heart failure. All data were pooled as either Mean difference in the random effect model with the corresponding SD or pooled as RR and 95% CI for dichotomous data. Results Twelve RCTs involving 6800 patients were included in the analysis. The overall effect on the measured primary outcomes was in favour of IV iron in terms of 6MWT mean change (MD= 34.45, 95% CI [ 29.58 to 39.31], P=<0.0001), ferritin concentration mean change (MD= 219.18, 95% CI [ 208.7 to 229.66], P=<0.0001), transferrin saturation mean change (MD= 9.77, 95% CI [ 8.14 to 1.39], P=<0.0001) and worsening heart failure (RR= 0.46, 95% CI [ 0.31 to 0.69], P=0.002). Conclusion The introduction of the IV iron therapy to heart failure patients showed a beneficial effect in terms of the measured haematological and cardiovascular metrics, which include 6MW test mean change, ferritin concentration mean change, and worsening heart failure.6MWT mean changeFerritin mean change

Ferroptosis contributes to the development of cardiac dysfunction in iron overload cardiomyopathy

Abstract Background Ferroptosis is a novel form of cell death, and its role in iron overload cardiomyopathy (IOC) has not been elucidated. Purpose To explore whether ferroptosis of cardiomyocytes contributes to cardiac dysfunction in IOC by cardiac MR (CMR) and molecular biology techniques in vivo. Methods A total of 14 Sprague-Dawley (SD) rats were randomly divided into two groups: the control group (n=6) and the IOC group (n=8). The latter was induced by intraperitoneal injection of iron dextran on alternate days for 9 weeks and underwent a 7T CMR for assessment of cardiac function, including left ventricular ejection fraction (LVEF) and global longitude strain (GLS), along with the assessment of iron overload severity and fibrosis using Cine, T2 mapping, and late gadolinium enhancement (LGE), respectively. Circulating iron overload was determined via blood biochemistry analysis, measuring serum iron, ferritin, and transferrin levels. Furthermore, Prussian blue and Masson staining were employed to identify iron and fibrosis deposition within the myocardium, respectively. Cardiac ultrastructure, especially mitochondria, was examined via transmission electron microscopy (TEM). A sensitive fluorescent probe, dihydroethidium (DHE), was employed for the detection of reactive oxygen species (ROS) levels. Malondialdehyde (MDA), prostaglandin-endoperoxide synthase 2 (PTGS2), and glutathione peroxidase 4 (GPX4) were utilized to identify and quantify levels of lipid peroxidation, thereby providing comprehensive insights into cardiac cellular ferroptosis. Results 6 rats survived in the control group and 5 in the IOC group. Compared with the control group, the IOC rats had reduced T2 values of the cardiac septum (P<0.001), with normal LVEF (P>0.05) but decreased GLS (P<0.01), seen in Fig 1A. Based on blood biochemistry and Prussian blue staining, they were evident that IOC rats exhibited both circulating and cardiac iron overload, as seen in Figure 1B, C. Masson staining showed no obvious myocardial fibrosis, which was consistent with negative CMR LGE results, seen in Fig 1A, B. TEM further elucidated cardiac mitochondrial injuries in IOC rats, including focal vacuolization, swelling, crest disruption, and even disappearance, seen in Fig 2A. The fluorescent probe results revealed a striking increase in red fluorescence within the myocardium of IOC rats, seen in Fig 2B. Additionally, IOC rats exhibited significantly elevated levels of MDA and PTGS2mRNA (P<0.001), accompanied by notable downregulation of GPX4mRNA expression (P<0.001), seen in Fig 2C. These findings suggested the occurrence of ferroptosis in the myocardium of IOC rats. Conclusions In IOC, ferroptosis rather than necrosis is the primary driver of cardiac dysfunction, which is characterized by maintaining normal LVEF but experiencing a reduction in GLS without accompanying myocardial fibrosis. Our study sheds light on the potential involvement of ferroptosis in the pathogenesis of IOC.

Iron chelation therapy failed to improve cardiac dysfunction caused by mitochondrial injury in rats with iron overload cardiomyopathy a 7T Cardiac MR research in vivo

Abstract Purpose To assess the efficacy of iron chelation therapy in improving cardiac function in iron overload cardiomyopathy (IOC) rats by using Cardiac magnetic resonance feature-tracking (CMR-FT). Methods The IOC rat model was induced by intraperitoneal injection of iron dextran over 2 months. Subsequently, 7 rats with IOC were assigned as IOC group to receive continued intraperitoneal injections of saline for an additional 2 months, while another group of 5 rats received intraperitoneal injections of deferoxamine (DFO) for the same duration, forming the IOC+DFO group. Meanwhile, a control group consisting of 7 healthy rats received intraperitoneal injections of saline for the entire duration of 4 months. All rats underwent a 7T CMR scan to assess cardiac function, myocardial iron overload, and myocardial fibrosis via cine, T2 mapping, and late gadolinium enhancement (LGE) scanning, respectively. The cardiac function analysis included left ventricular ejection fraction (LVEF) and left ventricular global longitudinal strain (GLS) using cine images. Following CMR scans, all rats underwent open-chest blood collection to detect serum iron levels, and cardiac gross specimens were then subjected to pathological staining, including hematoxylin and eosin (HE) for cardiomyocytes injury, Prussian blue for iron deposition , and Masson staining for myocardial fibrosis. Furthermore, the ultrastructure of cardiomyocyte was examined using transmission electron microscopy (TEM). Results The T2 value, measured in the septum wall at the mid-layer of the LV, and LVEF, and GLS exhibited a significant decrease in the IOC or IOC+DFO group, compared to the control group, while there were no significant difference observed between the IOC and IOC+DFO group (Fig. 1A, B, C). Myocardial fibrosis was not detected in the LGE images in both IOC and IOC+DFO group. Compared to the control group (37.5±12.5μmol/L) , serum iron levels were significantly elevated in the IOC group (368.6±181.0μmol/L) and in chelation treatment group (106.1±32.2μmol/L). Histological examination with HE staining revealed a normal arrangement of myocardial cells in all rats, without cellular degeneration or necrosis. Prussian blue staining highlighted the presence of iron particles within the myocardial interstitium in the IOC and IOC+DFO groups. Masson staining demonstrated intact myocardial muscle bundles without any evidence of myocardial fibrosis. Transmission electron microscopy (TEM) revealed myocardial mitochondria injury, characterized by ruptured outer membranes, reduced cristae, and vacuolization. Conclusions Following iron chelation therapy, the excessive iron burden in the bloodstream was alleviated. However, myocardial iron overload persisted in IOC rats, with no significant improvement in cardiac function observed. This persistence may be attributed to mitochondrial injury. The findings underscore the importance of monitoring cardiac dysfunction in patients with iron overload.CMR parameters analysis in IOC rats

Impact of global longitudinal strain and anemia for predicting cardiovascular mortality in patients hospitalized for acute heart failure with atrial fibrillation

Abstract Background Iron deficiency is a prognostic factor in heart failure (HF) with reduced ejection fraction (EF). In patients with atrial fibrillation (AF) and HF, left ventricular EF (LVEF) measurements are imprecise due to irregular tachycardia, but it is unclear whether global longitudinal strain (GLS) and anemia assessment are prognostic. Purpose We examined whether GLS and anemia predict cardiovascular death (CD) in patients with acute HF complicated by AF. Methods We retrospectively enrolled patients aged 18 years or older with acute HF complicated by AF who were consecutively admitted to our hospital from January 2014 to December 2018. Exclusion criteria were acute coronary syndromes, no transthoracic echocardiogram performed within 30 days before or after admission, and missing data. All patients were followed up from admission to CD (due to myocardial infarction, HF, stroke or sudden death), or were censored at the date of last contact or 3 years. Anemia was defined as hemoglobin < 12 g/dL in females and hemoglobin < 13 g/dL in males. Patients were divided into four groups according to median GLS and anemia status. Results A total of 320 patients (mean age 79 ± 12 years, 163 females) were included in the analysis. The median duration of AF was 1.2 years; 11% (36/320) had paroxysmal AF. The median brain natriuretic peptide value was 623 pg/ml, and 52% of the patients (165/320) were in New York Heart Association functional class 4. During a median follow-up of 528 days, 24% (77/320) patients were observed with CDs: 2 myocardial infarctions, 51 HF-related deaths, 6 strokes, and 18 sudden cardiac deaths. At the 3-year follow-up, the survival rate by the Kaplan-Meier curve was 89% (95% confidence interval (CI) 76%-95%) in the no anemia group with high GLS (< -10%) and 40% (95% CI 25%-54%) in the anemia group with low GLS (≥ -10%) (p < 0.001, log-rank test). In multivariate Cox regression analysis, GLS (adjusted hazard ratio (aHR) 1.06, 95% CI 1.01-1.14, p = 0.017) and hemoglobin (aHR 0.85, 95% CI 0.76-0.96, p = 0.009) were independent factors for CD, with a significantly increased risk in the anemia group with low GLS compared to the no anemia group with high GLS (aHR 4.11, 95% CI 1.59-10.6, p = 0.004). The results were consistent with no interaction by gender or LVEF 50%. Conclusions Anemic patients with low GLS with AF and HF may have poor prognosis. Prospective studies are needed to determine whether iron supplementation improves prognosis in such patients.

Effects of eHealth literacy on maternal and neonatal outcomes

ABSTRACT eHealth literacy plays a crucial role during pregnancy, as maternal health behavior can influence health outcomes for both mother and child. This study assessed the impact of eHealth literacy on maternal-fetal health outcomes through a cross-sectional analysis of 1,265 pregnant women admitted to a tertiary maternity hospital in Turkey between April and July 2022. Data on sociodemographic information, obstetric variables, birth outcomes, Internet usage, and eHealth Literacy Scale (eHEALS) were collected. Kolmogorov-Smirnov, Mann – Whitney U, Kruskal-Wallis, and Spearman correlation were used for data analysis. The median age of women was 28 years, and the mean gestational age was 38.6 weeks. Median eHealth literacy score was 21 (range:8-40). Pregnant women who had planned pregnancies, received spousal support, attended 9–12 antenatal care visits, received vaccinations, adhered to iron and folic acid supplementation, engaged in regular physical activity, and maintained regular sleep patterns exhibited higher eHealth scores (all p < .001). eHEALS scores were higher in women who experienced normal vaginal deliveries (p < .001), while lower eHEALS scores were noted in those with comorbidities (p = .001). The study suggested that higher eHealth literacy among pregnant women was associated with improved health-promoting behaviors, more favorable health perceptions, increased utilization of health services, and better maternal and fetal outcomes.

Safety of an Accelerated Ferric Gluconate Inpatient Infusion Regimen

Background: Inpatient use of intravenous iron has been increasing. Ferric gluconate is traditionally given once daily. Twice-daily dosing provides faster iron repletion, but there are limited data to support the safety of twice-daily dosing. Objective: The aim of this study was to investigate the safety of twice-daily dosing for ferric gluconate compared with daily dosing. Methods: This was an institutional review board-approved retrospective observational study of hospitalized adult patients who received intravenous ferric gluconate 250 mg daily or twice daily between January 1 and April 3, 2022. The primary composite safety outcome included hypotension, infusion reaction, rapid response alert, or escalation in level of care. Secondary outcomes included total amount of iron received, hospital length of stay, and changes in laboratory values. Results: A total of 126 patients were included in this study, with 63 patients in each group. The primary outcome occurred in 29 patients (46%) in the twice-daily group compared with 36 patients (57.1%) in the daily group (relative risk = 0.81; 95% CI, 0.57-1.13; P = 0.212). Changes in iron, hemoglobin, and transferrin saturation were similar between the 2 groups. Median length of stay was statistically shorter in the twice-daily group (7.79 days) compared with the daily group (12.9 days; p = 0.006). Conclusions: In this retrospective single-center study of hospitalized adult patients, those who received intravenous ferric gluconate twice daily did not experience an increased rate of a composite safety outcome of hypotension, infusion reactions, or escalation in level of care compared with those with daily dosing.

Mid-term efficacy of single anastomosis duodenal-ileal bypass with sleeve gastrectomy in the treatment of obesity and type 2 diabetes mellitus

Objective: To evaluate the mid-term efficacy of single anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADI-S) in the treatment of obesity and type 2 diabetes mellitus. Methods: The cohort of this retrospective observational study comprised 118 obese patients with body mass index (BMI) ≥40 kg/m2 with or without other related metabolic diseases and BMI of (27.5-40.0) kg/m2 with type 2 diabetes mellitus (T2DM) who had been treated with SADI-S. Patients who had undergone modified surgery or been followed up for less than 1 year were excluded. Clinical data of the included patients [56 men and 62 women aged (34.5±9.7) years], who had undergone SADI-S in China-Japan Union Hospital, Jilin University from October 2018 to August 2022, were collected. Their mean preoperative body mass was (125.9±25.0) kg and BMI (42.8±6.8) kg/m2. The 60 patients with T2DM had a mean fasting blood glucose of (9.9±3.2) mmol/L and HBA1c of (8.4±1.7) % before surgery. The main outcome measures were mid-term weight loss after surgery (body mass, BMI, excess weight loss, and total weight loss) 1, 2, 3, and 4 years after surgery and efficacy regarding diabetes mellitus (fasting blood glucose, glycated hemoglobin and diabetes remission rate at 1, 2, and 3 years after surgery). Outcomes were defined as follows. Complete remission: HbA1c <6% or fasting blood glucose <6 mmol/L without hypoglycemic medication; partial remission: HBA1c <6.5% or fasting blood glucose <7 mmol/L without hypoglycemic medication; significant improvement: HBA1c <7.0%, stable decrease of at least 1% compared with preoperative HBA1c, and postoperative dose of hypoglycemic medication significantly less; ineffective: no change in HBA1c and no reduction in dosage of hypoglycemic medication. Other outcome measures included intraoperative and postoperative adverse effects and postoperative nutritional indexes. Results: SADI-S was successful in all patients. There was no significant bleeding, conversion to open surgery, or perioperative death. The operation time was (186.1±41.5) minutes, and the postoperative hospital stay 6 (5-7) days. Surgical complications occurred in four patients, comprising peritoneal effusion, internal jugular vein thrombosis, anastomotic leakage, and gastric fistula. Body weight and BMI 1, 2, 3 and 4 years were significantly lower post- than pre-operatively (all P<0.05). Excess weight loss was (81.9±16.2) %, (82.2±15.5) %, (88.3±20.1) %, and (83.2±18.1) % at 1, 2, 3, and 4 years postoperatively, respectively. Total weight loss was (39.7±8.7) %, (40.6±10.6) %, (42.2±11.5) % and (45.4±10.2) %, respectively. The mean fasting blood glucose concentrations of the 60 patients with T2DM were (5.1±1.0) mmol/L, (5.0±0.7) mmol/L, and (5.4±0.9) mmol/L 1, 2 and 3 years postoperatively, respectively. The values for glycosylated hemoglobin were (4.9±0.6) %, (4.8±0.5) %, and (5.1±0.8) %, respectively, all of which are significantly lower than preoperatively (all P<0.05). The complete remission rate of diabetes was 95.0% (38/40), 90.0% (36/40), and 9/13 1, 2, and 3 years postoperatively, respectively. Additionally, the partial remission rate and significant improvement rate were both 100%. Two years postoperatively, the incidence of anemia was 27.8% (10/36), of hypoproteinemia 11.8% (4/34), and of ferritin deficiency 25.8% (8/31), all of which were improved by conservative treatment such as blood transfusion, iron supplementation, and adjustment of diet. Conclusion: SADI-S has a significant mid-term beneficial effect on weight loss and diabetes remission status in patients with obesity and type 2 diabetes.

Effect of correcting iron deficiency on the risk of serious infection in heart failure: Insights from the IRONMAN trial.

Concerns exist that intravenous (IV) iron might increase the risk of infections. The IRONMAN trial provided an opportunity to investigate whether giving IV ferric derisomaltose (FDI) to patients with heart failure and iron deficiency alters the rate of hospitalization or death due to infections. IRONMAN was a randomized trial of IV FDI versus usual care in patients with symptomatic heart failure, left ventricular ejection fraction (LVEF) ≤45%, and transferrin saturation (TSAT) <20% or ferritin <100 μg/L. Infection was a pre-specified, blindly-adjudicated, safety endpoint. The primary analysis of interest was infection as the main reason for hospitalization or death, using first and recurrent events analyses. The composite primary event of interest tended to be lower in those randomized to FDI when analysed as first (hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.62-1.01, p = 0.055) or recurrent event (rate ratio 0.85, 95% CI 0.64-1.13, p = 0.089). The composite results were driven by fewer hospitalizations for infection (HR 0.76, 95% CI 0.49-0.98, p = 0.032), with 5% fewer patients (absolute reduction) experiencing such an event if assigned to FDI. Similar trends were observed for recurrent events (HR 0.82, 95% CI 0.62-1.10). Further analyses suggested that the reduction in hospitalizations due to infection with FDI was restricted to patients with TSAT <20%. In patients with heart failure and a reduced LVEF, correction of iron deficiency is not associated with an increased risk of hospitalization or death from infection, and may reduce such events, especially when TSAT is <20%. ClinicalTrials.gov, NCT02642562.

Case report: exome sequencing identified mutations in the LRP5 and LGR4 genes in a case of osteoporosis with recurrent fractures and extraskeletal manifestations

BackgroundGenetic mutations have been reported in a number of bone disorders with or without extra-skeletal manifestations. The purpose of the present study was to investigate the genetic cause in a middle-aged woman with osteoporosis, recurrent fractures and extraskeletal manifestations.MethodsA 56-year-old Indian woman presented to the clinic with complaints of difficulty in walking, recurrent fractures, limb bending, progressive skeletal deformities, and poor overall health. At the age of 37, she had experienced severe anemia with diarrhea, significant weight loss, knuckle pigmentation, and a significant loss of scalp hair. She had received multiple blood transfusions and parenteral iron supplementation with normalization of hemoglobin. Subsequently, she had premature menopause at the age of 37. She died at the age of 61 due to liver failure. Exome sequencing followed by Sanger sequencing were undertaken to identify the potential pathogenic mutations.ResultsGenetic investigation identified likely pathogenic mutations in the LRP5 and LGR4 genes. Out of the two mutations, the heterozygous mutation (c.1199C&amp;gt;T) in the LRP5 gene resulted in a non-synonymous substitution of alanine with valine at the 400th position, and the second mutation (c.1403A&amp;gt;C) in the LGR4 gene led to a non-synonymous substitution of tyrosine with serine at the 468th residue of the protein. The minor allele frequencies of the c.1199C&amp;gt;T (LRP5) substitution in the 1000 genomes and IndiGenomes databases are 0.0003 and 0.001, while the c.1403A&amp;gt;C (LGR4) substitution has not been reported in these databases. Various in silico prediction tools suggested LGR4 mutation to be pathogenic and LRP5 mutation to be likely pathogenic.ConclusionHeterozygous mutations in the LRP5 and LGR4 genes had additive deteriorative effects on BMD, resulting in recurrent fractures and bone deformities, and extended the effect to extraskeletal sites, contributing to the poor overall health in this patient.

An assessment of adequate quality antenatal care and its determinants in India

BackgroundAntenatal care (ANC) is an important component in the continuum of care. Providing adequate quality ANC is necessary to prevent maternal and newborn mortality. The coverage of ANC has increased significantly in the last decade in India, but a mere increase in coverage is insufficient if the issue of quality is not simultaneously addressed. This study examines the change in each component of quality ANC between 2015-16 and 2019-21, highlights the factors associated with adequate quality ANC, and observes the state- and district-level distribution of adequate quality ANC during 2019-21.MethodsThis study is based on data from the two most recent rounds of the National Family Health Survey (NFHS), the Indian equivalent of the Demographic and Health Surveys (DHS). These rounds were conducted in 2015-16 and 2019-21 in selected households of India with a total of 190,797 and 176,843 sampled births, respectively. The dependent variable was quality antenatal care, a composite variable consisting of skilled healthcare providers, timeliness, sufficiency, and appropriateness of content. The independent variables were mother’s age, education, wealth quintile, birth order, mass media exposure, health insurance coverage, relationship with the head of household, facility exposure, intended pregnancy, history of adverse pregnancy outcomes, and other socio-demographic variables. Change in each component and dimension of quality antenatal care was assessed using data from both rounds of the survey. A multivariate multinomial logistic regression analysis was employed to identify the determinants of adequate quality ANC using the NFHS-5 data.ResultsThe findings revealed that 32 per cent of mothers received adequate quality antenatal care in 2019–2021, an increase of only 9% points compared to the 2015-16 period. Two significant barriers to achieving adequate quality antenatal care, in terms of appropriateness of content, were the provision of Iron and Folic Acid (IFA) tablets and counselling. The highest utilisation of adequate quality antenatal care was observed in the southern states. The utilisation of quality ANC increased with an increase in women’s education and wealth status; and was more prevalent among those with health insurance coverage and exposure to mass media.ConclusionDespite some improvements in the coverage of antenatal care, the quality of antenatal care continues to be very low and needs urgent attention. Achieving quality antenatal care in both content and experience requires addressing service gaps and developing better measures to capture and improve women’s care experiences.

56 Iron deficiency is common in extreme preterm infants despite prophylactic iron supplementation

Abstract Background Iron deficiency (ID) in childhood is linked to adverse neurodevelopmental outcomes in the long-term. Extremely premature infants (EPI; born &amp;lt; 28 weeks gestation) are more susceptible to ID due to a multitude of factors including lower iron reserves at birth, rapid growth, immature erythropoiesis, and multiple phlebotomy tests during hospital stay. Therefore, professional societies advise prophylactic iron therapy for these infants from 2-6 weeks age until 6-12 months. However, there is paucity of data on the iron status in EPI receiving this prophylactic iron supplementation. Objectives To investigate the prevalence and risk factors associated with ID in EPI. Design/Methods A retrospective cohort study analyzed a Provincial database of EPIs born between 2005-2018. Infants with congenital malformations, chromosomal anomalies and blood disorders were excluded. All included infants received prophylactic iron supplementation from 2-4 weeks of chronological age that was recommended to continue at discharge until 9-12 months corrected age (CA). At 4-6 months CA, these infants underwent blood testing. ID was defined as serum ferritin &amp;lt; 20mcg/L at 4 months CA or SF &amp;lt; 12mcg/L at 6 months CA. Through a univariate analysis using single-variable logistic regression, factors linked to ID were identified. Those with a p-value &amp;lt; 0.20 progressed to a multivariable model, retaining variables with a p-value &amp;lt; 0.05. Results Of 146 infants, 45.9% had ID. ID group had lower mean ferritin (16.4 µg/L vs 50.0 µg/L, p &amp;lt; .001) and reticulocyte hemoglobin equivalent (28.4pg vs 31.6pg, p &amp;lt; .001) compared to the non-ID group. ID prevalence reduced from 59.7% in 2005-2011 to 40.3% in 2012-2018 cohort. Exclusive or partial breastfeeding at 4-6 months CA was protective against ID (Odds: 0.2, p = 0.003). Iron therapy at 4-6 months CA was not protective in the final model. Notably, 27.4% stopped iron therapy before 4-6 months CA, and exclusive formula-fed infants had notably lower iron intake than breastfed infants (66.1% vs 99.1%, p = 0.006). Conclusion Nearly half of the EPI exhibited ID at 4-6 months CA despite prophylactic iron supplementation. About a quarter discontinued therapy before reaching this age. Breastfeeding at this age was protective against ID. This high prevalence of ID in EPI underscores the need of future studies to discern strategies to mitigate ID in this vulnerable population.

Influence of iron deficiency definition on the efficacy of intravenous iron in heart failure: a meta-analysis of randomized trials.

Intravenous iron improves symptoms in heart failure (HF) with iron deficiency (ID) but failed to consistently show a benefit in cardiovascular outcomes. The ID definition used may influence the response to intravenous iron. The aim of this meta-analysis is to assess the influence of ID definition on the intravenous iron effect in HF. We performed a random-effects meta-analysis of randomized controlled trials (RCT) on intravenous iron (vs. placebo or standard of care) in patients with HF and ID that provided data on transferrin saturation (TSAT) and ferritin subgroups on the composite outcome of cardiovascular death (CVD) or HF hospitalizations (HFH). The risk ratio (RR) and 95% confidence intervals (95% CI) were extracted on the TSAT (< 20% and ≥ 20%) and ferritin (< 100ng/mL and ≥ 100ng/mL) subgroups. Data from four major RCT was collected including a total of more than 5500 patients. In patients with a TSAT < 20%, intravenous iron reduced the composite outcome of CVD or HFH: RR 0.81, 95%CI 0.69-0.94, while in patients with a TSAT ≥ 20% the effect was neutral: RR 0.98, 95%CI 0.79-1.21, interaction, P = 0.05. On the other hand, ferritin levels did not modify the effect of IV iron: ferritin ≥ 100ng/mL RR 0.84, 95%CI 0.65-1.09, and ferritin < 100ng/mL RR 0.85, 95%CI 0.74-0.97; interaction, P = 0.96. Our meta-analysis suggests that the benefit of intravenous iron may be restricted to patients with TSAT < 20% regardless of ferritin levels and supports the single use of TSAT < 20% to identify patients with ID who may benefit from intravenous iron therapy.

Effect of Enamel Surface Coating on Staining Capability Due to Iron-Containing Supplements on Primary Teeth: An in Vitro Study

ABSTRACT Background: The staining of primary teeth due to iron-containing supplements is a common concern among parents and healthcare providers. Materials and Methods: Forty extracted primary teeth were divided into two groups of 20 each. Group A served as the control and received no enamel coating, while Group B was treated with a commercially available enamel surface coating. Both groups were then exposed to iron-containing supplements for 7 days. The teeth were assessed for color changes using a spectrophotometer before and after exposure. The degree of staining was quantified using the CIELAB color space values, specifically the ΔE* value, which indicates the change in color. Results: The mean ΔE* value in Group A (control) was 12.5 ± 1.8, indicating significant staining. In contrast, Group B (coated) showed a mean ΔE* value of 4.2 ± 1.1, reflecting minimal staining. The difference between the two groups was statistically significant (P &lt; 0.001), demonstrating the effectiveness of the enamel surface coating in reducing staining caused by iron supplements. Conclusion: Enamel surface coatings significantly reduce the staining effect of iron-containing supplements on primary teeth.

Intravenous iron staining: real-world incidence, preventability, and mitigation tools from a long-term quality improvement project.

Iron deficiency is the leading cause of anaemia worldwide and is increasingly treated with intravenous (IV) iron therapy. Staining from IV iron therapy is a rare but significant and preventable adverse event. To mitigate patient harm, a health-service-wide quality improvement project was implemented. This study aimed to determine the real-world impact of a quality improvement project on IV iron staining incidents and preventability. A retrospective chart audit was undertaken for all IV iron staining episodes reported in a directorate-wide clinical incident reporting database (RiskMan) between 2016 and 2022. Incidence rates of IV iron staining, preventability, and stain severity were compared pre- and post-implementation of a standardized IV iron procedure. Over 7 years, 103 IV iron stains were identified, resulting in a staining rate of 0.31 stains per 100 infusions (pre 0.27% and post 0.34%, P = .25). Implementation of the standardized IV iron procedure resulted in improvements in pharmacist review of the medication order (61.8% versus 89.7%, P < .01), use of the statewide IV iron infusion consent form (27.3% versus 76.9%, P < .01), and appropriate cannula site (14.3% versus 52.5%, P < .01). Smaller stain sizes were associated with cessation of the infusion at identification of extravasation (312 cm2 versus 35 cm2) (P = .04). Preventability was assigned to 86% of stains. The incidence rate of IV iron staining in a real-world clinical setting is 0.31%. There was increased compliance with several best practice principles and 86% of stains were preventable. Early identification and intervention of potential staining incidents results in smaller iron stains for patients. Quality improvement tools developed for this project can contribute to patient outcomes internationally.

Trends in the quality of antenatal care in India: Patterns of change across 36 states and union territories, 1999-2021.

Antenatal care (ANC) quality is important to maternal and neonatal mortality. However, trends in the quality of ANC received by pregnant women in India have been understudied. This paper seeks to fill this gap by examining the long-term patterns nationwide and the state-specific prevalence of inadequate ANC quality received by pregnant women in India. We utilised data from four National Family Health Surveys (NFHS) conducted in 1999 (NFHS-2), 2006 (NFHS-3), 2016 (NFHS-4), and 2021 (NFHS-5) across India's 36 states/union territories (UTs). The sample includes mothers who had given birth within three years (NFHS-2) and five years (NFHS-3, NHFS-4, and NFHS-5) before each survey. We define inadequate ANC quality as not completing seven essential ANC services (weight measurement, blood pressure measurement, urine sampling, blood sampling, provision of iron supplements, provision of tetanus vaccination, and ultrasound scans) during pregnancy. We calculated the standardised absolute change to quantify the change in the share of women receiving inadequate quality ANC nationally and by each state/UT. Additionally, we estimated the population headcount of mothers who received inadequate-quality ANC in 2021 and identified the socioeconomic correlates associated with inadequate ANC quality. The prevalence of inadequate ANC quality substantially declined between 1999-2021, from 84.8% (95% confidence interval (CI) = 84.1-85.5) to 28.8% (95% CI = 28.5-29.2). However, between-state inequality in ANC quality has increased over this time. We identified a weak correlation between prevalence and population headcounts in 2021. Socioeconomically disadvantaged groups exhibited a higher prevalence of inadequate quality of ANC than less disadvantaged groups. The proportion of pregnant women receiving inadequate ANC quality has decreased over time throughout India. However, multi-faceted efforts at national and state levels are necessary to enhance the effectiveness of existing policies. Additionally, innovative and targeted approaches are required to ensure the timely and equitable provision of high-quality ANC.

Iron Deficiency Anaemia in Pregnancy: A Narrative Review from a Clinical Perspective.

Anaemia in pregnancy is a global problem of significance in all settings. The most common cause is iron deficiency. Large numbers of women are affected, ranging up to 25-30% antenatally and 20-40% postnatally. It is associated with serious adverse outcomes for both the mother and her baby. The risk of low birth weight, preterm birth, postpartum haemorrhage, stillbirth, and neonatal death are all increased in the presence of anaemia. For the infants of affected pregnancies, complications may include neurocognitive impairment. Making an accurate diagnosis during pregnancy has its challenges, which include the choice of thresholds of haemoglobin below which a diagnosis of anaemia in each trimester of pregnancy can be made and, aligned with this question, which are the most appropriate biomarkers to use to define iron deficiency. Treatment with oral iron supplements increases the haemoglobin concentration and corrects iron deficiency. But high numbers of women fail to respond, probably due to poor adherence to medication, resulting from side effects. This has resulted in an increased use of more expensive intravenous iron. Doubts remain about the optimal regimen to of oral iron for use (daily, alternate days, or some other frequency) and the cost-effectiveness of intravenous iron. There is interest in strategies for prevention but these have yet to be proven clinically safe and effective.

Hepcidin Modulators: A Potential Alternative Treatment of Iron Deficiency and Iron Deficiency Anemia in Heart Failure

Heart failure affects roughly 6.7 million Americans and is associated with many comorbidities and complications, including iron deficiency and anemia. Iron homeostasis is integral to optimal body function. Hepcidin, a hepatically produced peptide, is a major modulator in iron homeostasis. Its synthesis is induced in part by inflammatory states. Iron deficiency in heart failure is currently diagnosed with the assessment of serum ferritin and percent of transferrin saturation. Iron deficiency in the setting of hepcidin excess in inflammatory conditions, such as heart failure, is discussed in this literature review. Iron deficiency is associated with worse prognosis and poorer outcomes in heart failure patients. Targeted treatment of iron deficiency and iron deficiency anemia may provide improved quality of life and decrease mortality and morbidity among heart failure patients. Current treatment options for iron deficiency and anemia include intravenous and oral iron supplementation, as well as other erythropoiesis-stimulating agents. However, concerns regarding safety have been raised in regards to these options. An emerging possibility for the treatment of iron deficiency in the setting of hepcidin overload is hepcidin modulators, including hepcidin antagonists or inhibitors. This review has addressed iron deficiency and anemia in heart failure and suggests that hepcidin antagonists/inhibitors may provide a viable alternative to the classic treatment methods.

Comparing The Effectiveness Of Intravenous Vs Oral Iron Therapy In Patients With Chronic Kidney Disease: Associated Anemia

Comparing The Effectiveness Of Intravenous Vs Oral Iron Therapy In Patients With Chronic Kidney Disease: Associated Anemia