Ferric carboxymaltose versus standard-of-care oral iron to treat second-trimester anaemia in Malawian pregnant women: a randomised controlled trial
Lancet (London, England). 2023
BACKGROUND Anaemia affects 46% of pregnancies in Africa; oral iron is recommended by WHO but uptake and adherence are suboptimal. We tested a single dose of a modern intravenous iron formulation, ferric carboxymaltose, for anaemia treatment in Malawian pregnant women. METHODS In this open-label, individually randomised controlled trial, we enrolled women with a singleton pregnancy of 13-26 weeks' gestation in primary care and outpatient settings across two regions in southern Malawi. Women were eligible if they had capillary haemoglobin of less than 10·0 g/dL and negative malaria rapid diagnostic test. Participants were randomised by sealed envelope 1:1. Assessors for efficacy outcomes (laboratory parameters and birthweight) were masked to intervention; participants and study nurses were not masked. Participants were given ferric carboxymaltose up to 1000 mg (given once at enrolment in an outpatient primary care setting), or standard of care (60 mg elemental iron twice daily for 90 days), along with intermittent preventive malaria treatment. The primary maternal outcome was anaemia at 36 weeks' gestation. The primary neonatal outcome was birthweight. Analyses were performed in the intention-to-treat population for mothers and liveborn neonates, according to their randomisation group. Safety outcomes included incidence of adverse events during infusion and all adverse events from randomisation to 4 weeks' post partum. The trial is registered with ANZCTR, ACTRN12618001268235. The trial has completed follow-up. FINDINGS Between Nov 12, 2018, and March 2, 2021, 21 258 women were screened, and 862 randomly assigned to ferric carboxymaltose (n=430) or standard of care (n=432). Ferric carboxymaltose did not reduce anaemia prevalence at 36 weeks' gestation compared with standard of care (179 [52%] of 341 in the ferric carboxymaltose group vs 189 [57%] of 333 in the standard of care group; prevalence ratio [PR] 0·92, 95% CI 0·81 to 1·06; p=0·27). Anaemia prevalence was numerically lower in mothers randomly assigned to ferric carboxymaltose compared with standard of care at all timepoints, although significance was only observed at 4 weeks' post-treatment (PR 0·91 [0·85 to 0·97]). Birthweight did not differ between groups (mean difference -3·1 g [-75·0 to 68·9, p=0·93). There were no infusion-related serious adverse events or differences in adverse events by any organ class (including malaria; ≥1 adverse event: ferric carboxymaltose 183 [43%] of 430 vs standard of care 170 [39%] of 432; risk ratio 1·08 [0·92 to 1·27]; p=0·34). INTERPRETATION In this malaria-endemic sub-Saharan African setting, treatment of anaemic pregnant women with ferric carboxymaltose was safe but did not reduce anaemia prevalence at 36 weeks' gestation or increase birthweight. FUNDING Bill & Melinda Gates Foundation (INV-010612).
Intravenous Iron Compared With Oral Iron Supplementation for the Treatment of Postpartum Anemia: A Randomized Controlled Trial
Obstetrics and Gynecology. 2023;141(6):1052-1055
Postpartum anemia is a significant maternal comorbidity that affects 50% of patients in the United States. It has been associated with maternal impaired cognition, depression, and fatigue, ultimately affecting mother–child bonding and neonatal care. Oral iron supplementation is currently the first-line treatment for women with iron-deficiency anemia postpartum. The effectiveness of oral iron is diminished by variability in absorption, discomforting side effects, and poor compliance, limitations that can be overcome with intravenous (IV) iron. However, IV iron is costly and needs to be administered under supervision in a hospital or outpatient clinical setting. We performed a pragmatic, double-blinded, feasibility randomized controlled trial of daily oral compared with IV iron administered after delivery but before hospital discharge. We found that patients randomized to IV iron had higher hemoglobin levels after 6 weeks postpartum than those randomized to oral iron. Our trial shows that it is feasible to administer IV iron during the delivery admission and that larger multicenter clinical trials are warranted. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, NCT05047211.
Identification and treatment of iron-deficiency anemia in pregnancy and postpartum: A systematic review and quality appraisal of guidelines using AGREE II
International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics. 2023
BACKGROUND Several international guidelines provide recommendations for the optimal management of iron-deficiency anemia (IDA) in the pregnant and postpartum populations. OBJECTIVES To review the quality of guidelines containing recommendations for the identification and treatment of IDA in pregnancy and postpartum using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument and to summarize their recommendations. SEARCH STRATEGY PubMed, Medline, and Embase databases were searched from inception to August 2, 2021. A web engine search was also performed. SELECTION CRITERIA Clinical practice guidelines that focused on the management of IDA in pregnancy and/or postpartum populations were included. DATA COLLECTION AND ANALYSIS Included guidelines were appraised using AGREE II independently by two reviewers. Domain scores greater than 70% were considered high-quality. Overall scores of six or seven (out of a possible seven) were considered high-quality guidelines. Recommendations on IDA management were extracted and summarized. MAIN RESULTS Of 2887 citations, 16 guidelines were included. Only six (37.5%) guidelines were deemed high-quality and were recommended by the reviewers. All 16 (100%) guidelines discussed the management of IDA in pregnancy, and 10 (62.5%) also included information on the management of IDA in the postpartum period. CONCLUSIONS The complex interplay of racial, ethnic, and socioeconomic disparities was rarely addressed, which limits the generalizability of the recommendations. In addition, many guidelines failed to identify barriers to implementation, strategies to improve uptake or iron treatment, and resource and cost implications of clinical recommendations. These findings highlight important areas to target future work.
Randomized Controlled Trial Comparing Ferrous Sulfate and Iron Sucrose in Iron Deficiency Anemia in Pregnancy
INTRODUCTION Anemia among pregnant women is one of the major health concerns for healthcare workers. The management becomes a concern in the pregnancy where the question arises of which is better the intravenous iron sucrose or the oral ferrous sulfate tablets. To answer this, a randomized control trial comparing both the treatment options in a tertiary care government hospital was set up in the hilly terrains of India. This study discusses the effectiveness and practical aspect of using both, which seems to be the better out of both, and why. METHODS The study was conducted as a parallel-group, open-label randomized controlled trial (RCT) in the Department of Obstetrics and Gynecology of a tertiary care government hospital in India, with approximately 4,000 delivery loads annually. Ethical clearance was obtained from the institute's ethics committee (IEC), and the trial was registered with the Clinical Trial Registry of India (REF/2022/06/055013). Two hundred sixty-eight pregnant women between 18 and 45 years of age with moderate iron deficiency anemia (IDA) (hemoglobin (Hb) 7-9g/dl, microcytic-hypochromic, and serum ferritin <30ng/ml) were included in the study. Patients were randomly divided into two groups: group 1 with 134 patients to receive intravenous iron sucrose and group 2 with 134 patients to receive oral ferrous sulfate tablets. RESULTS The intravenous iron sucrose is superior in terms of tolerability and correction of iron deficiency anemia during pregnancy. CONCLUSION It yields a quicker rise in Hb and serum ferritin with no major side effects. In the difficult terrain of Himachal Pradesh, this makes IV iron sucrose a better option for anemic pregnant women who do not have easy access to health facilities resulting in a large number of them reaching hospitals with moderate to severe anemia at a later gestation.
Pregnant women with moderate iron deficiency anaemia (n= 268).
Intravenous iron sucrose (n= 134).
Oral ferrous sulfate tablets (n= 134).
All women were followed up at four weeks after drug administration and at 36 weeks of gestation to check for the rise in serum ferritin and haemoglobin (Hb). The mean Hb after four weeks of therapy was 11.76 ± 1.29g/dl and 10.84 ± 0.67g/dl in the intravenous iron sucrose and oral ferrous sulfate group, respectively. The Hb at four weeks post-treatment was significantly higher in the intravenous group compared to the oral group. The mean Hb (g/dl) at 36 weeks of gestation was 12 ± 1.1g/dl and 11.28 ± 0.59g/dl in the intravenous iron sucrose and oral ferrous sulfate groups, respectively. The difference between the two groups was statistically significant. The rise in haemoglobin was 3.48g/dl and was significantly high in the intravenous iron sucrose group compared to the oral ferrous sulfate group which was 2.39g/dl after four weeks of treatment. The rise was 3.6g/dl and 2.82g/dl in the intravenous iron sucrose and oral ferrous sulfate group, respectively, at 36 weeks of gestation, and the difference was significant.
Efficacy and safety of Mojeaga remedy in combination with conventional oral iron therapy for correcting anemia in obstetric population: A phase II randomized pilot clinical trial
PloS one. 2023;18(5):e0285474
BACKGROUND To our knowledge, there is no prior randomized trial on the efficacy of Mojeaga remedy (a special blend of Alchornea cordifolia, Pennisetum glaucum and Sorghum bicolor extracts) when co-administered with standard-of-care for correction of anemia in obstetrics practice. This study determined the efficacy, safety and tolerability of Mojeaga as adjunct to conventional oral iron therapy for correction of anemia in obstetric population. METHODS A pilot open-label randomized clinical trial. Participants with confirmed diagnosis of anemia in three tertiary hospitals in Nigeria were studied. Eligible participants were randomized 1:1 to either Mojeaga syrups 50 mls (200mg/50mls) administered three times daily in conjunction with conventional iron therapy (Mojeaga group) for 2 weeks or conventional iron therapy alone without Mojeaga (standard-of-care group) for 2 weeks. Repeat hematocrit level were done 2 weeks post-initial therapy. Primary outcome measures were changes in hematocrit level and median hematocrit level at two weeks post therapy. Maternal adverse events and neonatal outcomes (birth anomalies, low birthweight, preterm rupture of membranes and preterm labor) were considered the safety outcome measures. Analysis was by intention-to-treat. RESULTS Ninety five participants were enrolled and randomly assigned to the Mojeaga group (n = 48) or standard-of-care group (n = 47). The baseline socio-demographic and clinical characteristics of the study participants were similar. At two weeks follow-up the median rise in hematocrit values from baseline (10.00±7.00% vs 6.00±4.00%;p<0.001) and median hematocrit values (31.00±2.00% vs 27.00±3.00%;p<0.001) were significantly higher in the Mojeaga group. There were no treatment-related serious adverse events, congenital anomalies or deaths in the Mojeaga group and incidence of other neonatal outcomes were similar (p>0.05). CONCLUSION Mojeaga represents a new adjuvants for standard-of-care option for patients with anemia. Mojeaga remedy is safe for treating anemia during pregnancy and puerperium without increasing the incidence of congenital anomalies, or adverse neonatal outcomes. CLINICAL TRIAL REGISTRATION www.pactr.samrc.ac.za: PACTR201901852059636 (https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=5822).
Neonatal outcomes from a randomized controlled trial of maternal treatment of iron deficiency anaemia with intravenous ferumoxytol versus oral ferrous sulfate
American journal of obstetrics & gynecology MFM. 2023;:101063
BACKGROUND Anemia in pregnancy is common worldwide and has known maternal risks. The relationship between the types of treatment offered for maternal anemia and the effects on the fetus and newborn are largely uninvestigated. OBJECTIVE Investigate whether maternal treatment with intravenous ferumoxytol compared to oral ferrous sulfate results in an increase in neonatal hematologic and iron indices. These analyses were planned secondary outcomes and post-hoc analysis from the trial with a primary outcome of change in maternal hemoglobin. STUDY DESIGN A randomized controlled trial including 124 participants with anemia by WHO criteria was performed in which participants were allocated in a 1:1 ratio to either 2 infusions of 510mg of intravenous ferumoxytol or 325mg oral ferrous sulfate twice daily. Fetal monitoring was performed during each intravenous iron infusion. Standard univariable statistical techniques were used to compare groups and to investigate associations between maternal and neonatal hemoglobin and iron indices. RESULTS Cord blood hematological parameters were equivalent between groups. Hemoglobin was 15.7g/dL vs 15.4g/dL (p = 0.6) and hematocrit was 50.5% and 49.2% (p=0.4) in those randomized to intravenous ferumoxytol, and oral ferrous sulfate, respectively. Iron studies revealed higher cord blood ferritin concentrations in infants of participants treated with intravenous ferumoxytol (294 vs 186, p = 0.005). There were equivalent iron (158 vs 146, p = 0.4), transferrin (186 vs 196, p=0.4) and total iron binding capacity (246 vs 244, p=1) in neonates of participants receiving intravenous versus oral treatment. There were no effects of the infusions observed on cardiotocography. Gestational age at birth was equivalent between groups. We noted a larger birth weight in neonates of participants treated with intravenous ferumoxytol (3215g vs 3033g, p=0.09), which was not statistically significant. Post hoc analyses revealed a statistically significant correlation between neonatal ferritin and maternal hemoglobin (p=0.006) and neonatal ferritin and maternal ferritin (p=0.017) at admission for delivery. CONCLUSION Neonates born to participants who received intravenous ferumoxytol were born with higher ferritin concentrations in cord blood, at the same gestation with the same birthweight. Participants with higher hemoglobin and ferritin indices delivered infants with higher ferritin concentrations in cord blood.
Intravenous infusions of ferumoxytol compared to oral ferrous sulfate for the treatment of anemia in pregnancy: A randomized controlled trial
American journal of obstetrics & gynecology MFM. 2023;:101064
BACKGROUND Iron deficiency anemia in pregnancy is highly prevalent and presents significant risk to patients. Initial treatment is often with oral medication. We hypothesized that intravenous ferumoxytol would result in superior treatment of anemia as compared to oral ferrous sulfate. OBJECTIVE Investigate whether two infusions of intravenous ferumoxytol are superior to the use of twice-daily oral ferrous sulfate for the treatment of iron deficiency anemia in pregnancy. STUDY DESIGN A randomized controlled trial was performed in which anemic participants (hemoglobin <11gd/L and hematocrit <33%) were allocated to receive either two infusions of 510mg of intravenous ferumoxytol approximately 7 days apart or 325mg oral ferrous sulfate twice daily from enrollment to the end of their pregnancy. Participants were randomized in a 1:1 ratio to each treatment. Our primary outcome was change in maternal hemoglobin. Secondary outcomes included maternal iron indices, maternal safety and maternal tolerability. RESULTS There were 124 participants (N = 62 per group). In the intravenous iron group, the mean change in hemoglobin was 1.86 g/dL (95% CI 1.57 g/dL - 2.14 g/dL) and in the oral group was 0.79 g/dL (95% CI 0.42 g/dL - 1.17 g/dL) (p<0.0001). The median change in ferritin between groups was 64.5 (range 31 - 364) vs 8 (range -436 - +167) (p=0.0001). The median change in iron between groups was also statistically significant with 47.5 ug/dL (range -133 ug/dL - +664 ug/dL) in the intravenous group vs 8.5 ug/dL (range -313 ug/dL -+437 ug/dL) in the oral iron group (p=0.001). CONCLUSION Intravenous ferumoxytol was well-tolerated, and it was associated with statistically significant increases in maternal hemoglobin, hematocrit, iron, and ferritin compared to oral ferrous sulfate.
Incidence of postpartum depression after treatment of postpartum anaemia with intravenous ferric carboxymaltose, intravenous ferric derisomaltose or oral ferrous sulphate: A randomized clinical trial
European journal of obstetrics & gynecology and reproductive biology: X. 2023;20:100247
OBJECTIVES This study aimed to explore whether the type of iron preparation used to treat postpartum anaemia affects the incidence of postpartum depression and whether the risk of postpartum depression is higher in postpartum patients with anaemia who were adequately treated compared to the general postpartum population. STUDY DESIGN Single-center, open-label, randomized trial. Women were allocated to receive intravenous ferric carboxymaltose, intravenous ferric derisomaltose or oral ferrous sulphate. Intravenous iron was given in one or two doses, while ferrous sulphate as two 80 mg tablets once daily. Primary outcome was postpartum depression measured by Edinburgh Postnatal Depression Scale (EPDS) six weeks postpartum. Haematological parameters were analyzed as secondary outcomes. Kruskal-Wallis test was used for group comparison (p < 0.05 significant). The chi-square test was applied to compare categorical variables as well as the group of all subjects treated for anaemia in the study with the historical data for the Slovenian postpartum population. RESULTS Three-hundred women with postpartum anemia (hemoglobin < 100 g/L within 48-hours postpartum) were included between September 2020 and March 2022 in tertiary perinatal center. Most characteristics were similar across groups. EPDS score at six weeks postpartum did not differ between groups. The treatment modality of postpartum anaemia did not have a statistically significant effect on the EPDS score six weeks after treatment (p = 0.10), nor did it have a statistically significant effect on the difference in EPDS scores before and after treatment (p = 0.68). The proportions of participants who scored 10 or more points on the EPDS scores at six weeks postpartum were not statistically different between the groups (p = 0.79). The proportion of participants with an EPDS score of 10 or more at six weeks postpartum in the total study population did not differ significantly from previously reported proportion of postpartum women with EPDS score of 10 or more in the general population (12 % vs. 21 %; p < 0.001). CONCLUSIONS Maternal depression at 6 weeks postpartum did not differ in women treated for postpartum anemia with intravenous ferric carboxymaltose, intravenous ferric derisomaltose or oral ferrous sulphate. Participants with postpartum anaemia who are adequately treated with either oral or intravenous iron preparations are not at a higher risk of postpartum depression than the general population at six weeks postpartum.
Tranexamic acid for the prevention of postpartum bleeding in women with anaemia: Statistical analysis plan for the WOMAN-2 trial: an international, randomised, placebo-controlled trial
Gates open research. 2023;7:69
Background: Postpartum haemorrhage (PPH) is responsible for over 50,000 maternal deaths every year. Most of these deaths are in low- and middle-income countries. Tranexamic acid (TXA) reduces bleeding by inhibiting the enzymatic breakdown of fibrin blood clots. TXA decreases surgical bleeding and reduces deaths from bleeding after traumatic injury. When given within three hours of birth, TXA reduces deaths from bleeding in women with PPH. However, for many women, treatment of PPH is too late to prevent death. World-wide, over one-third of pregnant women are anaemic and many are severely anaemic. These women have an increased risk of PPH and are more likely to die if PPH occurs. There is an urgent need to identify ways to prevent severe postpartum bleeding in anaemic women. The WOMAN-2 trial will quantify the effects of TXA on postpartum bleeding in women with anaemia. Results: This statistical analysis plan (version 1.0; dated 22 February 2023) has been written based on information in the WOMAN-2 Trial protocol version 2.0, dated 30 June 2022. The primary outcome of the WOMAN-2 trial is the proportion of women with a clinical diagnosis of primary PPH. Secondary outcomes are maternal blood loss and its consequences (estimated blood loss, haemoglobin, haemodynamic instability, blood transfusion, signs of shock, use of interventions to control bleeding); maternal health and wellbeing (fatigue, headache, dizziness, palpitations, breathlessness, exercise tolerance, ability to care for her baby, health related quality of life, breastfeeding); and other health outcomes (deaths, vascular occlusive events, organ dysfunction, sepsis, side effects, time spent in higher level facility, length of hospital stay, and status of the baby). Conclusions: WOMAN-2 will provide reliable evidence about the effects of TXA in women with anaemia. Registration: WOMAN-2 was prospectively registered at the International Standard Randomised Controlled Trials registry ( ISRCTN62396133) on 07/12/2017 and ClinicalTrials.gov on 23/03/2018 ( NCT03475342).
A Randomised Controlled Trial to Compare Injection Ferric Carboxymaltose and Oral Iron in Treating Iron Deficiency Anemia During Pregnancy
Journal of obstetrics and gynaecology of India. 2022;72(6):492-496
INTRODUCTION Iron deficiency anemia (IDA) in pregnancy has a prevalence as high as 40-60% in different countries of the world. Oral iron is used to treat his commonest medical disorder in pregnancy. Ferrous sulphate is associated with considerable side effects. Ferric carboxymaltose (FCM) is a newer iron preparation which allows for single and higher dose (up to 1000 mg) of IV iron infusion. This study was conducted to compare the efficacy of FCM and FS in treating IDA during pregnancy. METHODS A randomised control trial was done at a tertiary care centres involving 362 women (181 women each in FS and FCM group). The pregnant anemic women with IDA were enrolled between 18 and 34 weeks of pregnancy. They were given 1000 mg of FCM iv as single dose or were given FS tablets twice daily (120 mg iron daily). The data were collected for rise in the Hb and serum ferritin over a period of 6 weeks. RESULTS Nine and 18 patients were lost to follow-up in the FCM and FS group, respectively. The data were analysed as per protocol analysis. FCM group women showed 2.6 gm% rise in Hb compared to 1.7 gm% of FS group. One hundred and sixty-six out of 172 women in FS group achieved anemia correction at 6 weeks. No difference was observed in the neonatal outcome. No major side effects were observed in the either group. CONCLUSION In our study, FCM was more effective than oral FS in increasing Hb in women with IDA during pregnancy. This clinical benefit with FCM was achieved without the concerns for safety and tolerability of the drug.