1.
Intravenous compared with oral iron for the treatment of iron-deficiency anemia in pregnancy: a systematic review and meta-analysis
Lewkowitz AK, Gupta A, Simon L, Sabol BA, Stoll C, Cooke E, Rampersad RA, Tuuli MG
Journal of perinatology : official journal of the California Perinatal Association. 2019
Abstract
OBJECTIVE To assess the effect of intravenous versus oral iron on hematologic indices and clinical outcomes for iron-deficiency anemia (IDA) in pregnancy. STUDY DESIGN Searches in Ovid Medline, Embase, SCOPUS, Cochrane Database, and ClinicalTrials.gov identified randomized-controlled trials comparing intravenous to oral iron for treating IDA in pregnancy. Primary outcomes were maternal hematologic indices at delivery. Secondary outcomes were blood transfusion, cesarean delivery, neonatal outcomes, and medication reactions. RESULTS Of 15,637 studies, 20 randomized trials met inclusion criteria and were analyzed. Mean hemoglobin at delivery (9 studies: WMD 0.66 g/dL (95% confidence Interval 0.31 -1.02 g/dL)) was significantly higher after intravenous iron therapy. Intravenous iron was associated with higher birthweight (8 studies: WMD 58.25 g (95% CI: 5.57-110.94 g)) but no significant differences in blood transfusion, cesarean delivery, or neonatal hemoglobin. There were fewer medication reactions with intravenous iron (21 studies: RR 0.34% (95% CI: 0.20-0.57)). CONCLUSION Intravenous iron therapy is associated with higher maternal hemoglobin at delivery with no difference in blood transfusion and fewer mild medication reactions.
2.
Safety and effectiveness of intravenous iron sucrose versus standard oral iron therapy in pregnant women with moderate-to-severe anaemia in India: a multicentre, open-label, phase 3, randomised, controlled trial
Neogi SB, Devasenapathy N, Singh R, Bhushan H, Shah D, Divakar H, Zodpey S, Malik S, Nanda S, Mittal P, et al
The Lancet. Global health. 2019;7(12):e1706-e1716
Abstract
BACKGROUND Intravenous iron sucrose is a promising therapy for increasing haemoglobin concentration; however, its effect on clinical outcomes in pregnancy is not yet established. We aimed to assess the safety and clinical effectiveness of intravenous iron sucrose (intervention) versus standard oral iron (control) therapy in the treatment of women with moderate-to-severe iron deficiency anaemia in pregnancy. METHODS We did a multicentre, open-label, phase 3, randomised, controlled trial at four government medical colleges in India. Pregnant women, aged 18 years or older, at 20-28 weeks of gestation with a haemoglobin concentration of 5-8 g/dL, or at 29-32 weeks of gestation with a haemoglobin concentration of 5-9 g/dL, were randomly assigned (1:1) to receive intravenous iron sucrose (dose was calculated using a formula based on bodyweight and haemoglobin deficit) or standard oral iron therapy (100 mg elemental iron twice daily). Logistic regression was used to compare the primary maternal composite outcome consisting of potentially life-threatening conditions during peripartum and postpartum periods (postpartum haemorrhage, the need for blood transfusion during and after delivery, puerperal sepsis, shock, prolonged hospital stay [>3 days following vaginal delivery and >7 days after lower segment caesarean section], and intensive care unit admission or referral to higher centres) adjusted for site and severity of anaemia. The primary outcome was analysed in a modified intention-to-treat population, which excluded participants who refused to participate after randomisation, those who were lost to follow-up, and those whose outcome data were missing. Safety was assessed in both modified intention-to-treat and as-treated populations. The data safety monitoring board recommended stopping the trial after the first interim analysis because of futility (conditional power 1.14% under the null effects, 3.0% under the continued effects, and 44.83% under hypothesised effects). This trial is registered with the Clinical Trial Registry of India, CTRI/2012/05/002626. FINDINGS Between Jan 31, 2014, and July 31, 2017, 2018 women were enrolled, and 999 were randomly assigned to the intravenous iron sucrose group and 1019 to the standard therapy group. The primary maternal composite outcome was reported in 89 (9%) of 958 patients in the intravenous iron sucrose group and in 95 (10%) of 976 patients in the standard therapy group (adjusted odds ratio 0.95, 95% CI 0.70-1.29). 16 (2%) of 958 women in the intravenous iron sucrose group and 13 (1%) of 976 women in the standard therapy group had serious maternal adverse events. Serious fetal and neonatal adverse events were reported by 39 (4%) of 961 women in the intravenous iron sucrose group and 45 (5%) of 982 women in the standard therapy group. At 6 weeks post-randomisation, minor side-effects were reported by 117 (16%) of 737 women in the intravenous iron sucrose group versus 155 (21%) of 721 women in the standard therapy group. None of the serious adverse events was found to be related to the trial procedures or the interventions as per the causality assessment made by the trial investigators, ethics committees, and regulatory body. INTERPRETATION The study was stopped due to futility. There is insufficient evidence to show the effectiveness of intravenous iron sucrose in reducing clinical outcomes compared with standard oral iron therapy in pregnant women with moderate-to-severe anaemia. FUNDING WHO, India.
3.
A randomised controlled trial to compare intravenous iron sucrose and oral iron in treatment of iron deficiency anemia in pregnancy
Gupta A, Manaktala U, Rathore AM
Indian Journal of Hematology & Blood Transfusion. 2014;30((2):):120-5.
Abstract
The aim of this study was to compare the efficacy and safety of intravenous iron sucrose with oral iron therapy in pregnant patients with anemia. The primary outcome of the study was increase in haemoglobin on day 7, 14 & 28 and rise of serum ferritin over 28 days. The study population consisted of 100 patients with singleton pregnancy between 24 and 34 weeks, hemoglobin levels between 7.0-9.0 gm/dL and serum ferritin levels less than 15 ng/mL. The participants in the oral group were given daily 180 mg elemental iron in three divided oral doses for 4 weeks. Total calculated dose of iron sucrose with a target hemoglobin of 11 gm %, was given in 200 mg dose on alternate days. Mean haemoglobin rise was 0.58 gm/dL in the IV group as compared to 0.23 gm/dL in the oral group on day 14 and 1.9 gm/dL in the IV group & 1.3 gm/dL in the oral group on day 28, (p <0.05). In the IV group, 76% of the subjects achieved haemoglobin levels of >11 gm% at the time of delivery, as compared to only 54% of the subjects in the oral group who achieved these levels. Serum ferritin value was significantly higher in the IV group, 37.45 + 5.73 ng/mL as compared to 13.96 + 1.88 ng/mL in the oral group at 4th week (p <0.001). There was no major side effect in the IV group. 36% subjects in the oral group developed gastrointestinal side effects & 10% of the subjects were non compliant. The rate of hemoglobin rise is faster with intravenous iron sucrose therapy as compared to oral iron therapy which can be beneficial in pregnant women presenting with anemia at a later period of gestation. Intravenous iron sucrose is very well tolerated during pregnancy.
4.
A randomised double-blind study comparing sodium feredetate with ferrous fumarate in anaemia in pregnancy
Sarkate P, Patil A, Parulekar S, Rege NN, Samant BD, Lokhande J, Gupta A, Kulkarni K
Journal of the Indian Medical Association. 2007;105((5):):278, 280-1, 284.
Abstract
Iron deficiency anaemia is a major health problem in India especially in women of reproductive age group. The World Health Organisation recommends that the haemoglobin concentration should not fall below 11. 0 g/dl at any time during pregnancy. The aim of study was to compare the efficacy and safety of two doses of sodium feredetate with ferrous fumarate in improving haemoglobin profile in pregnant anaemic women. Pregnant women with gestation period between 12 and 26 weeks having serum haemoglobin < 10 g/dl, serum ferritin levels less than 12 microg/l were included in the study. Patients were divided into 3 groups and drugs administered accordingly. A total of 48 patients were available for analysis which included 37 patients who had completed all the visits up to 75 days follow-up and 11 patients who were treatment failures. In group A combination of sodium feredetate (containing 33 mg of elemental iron) along with vitamin B12 (15 microg) and folic acid (1. 5 mg) was administered twice a day. In group B combination of sodium feredetate (containing 66 mg of elemental iron) along with vitamin B12 (15 microg) and folic acid (1. 5 mg) was administered twice a day. In group C combination of ferrous fumarate (containing 100 mg of elemental iron) along with vitamin B12 (15 microg) and folic acid (1. 5 mg) was administered twice a day. Patients were evaluated for Hb, RBC count, MCV, MCH and MCHC at day 0, 30, 45, 60 and 75. Serum ferritin, serum iron, TIBC and transferrin saturation were assessed at recruitment and end study. Mean rise of haemoglobin at the completion of study, over that of basal values was 1. 79 g/dl (0. 71 to 2. 87, 95% CI, p < 0. 05) in group A, 1. 84 g/dl (0. 82 to 2. 86, 95% CI, p < 0. 05) in group B and 1. 63 g/dl (0. 38 to 2. 88, 95% CI, p < 0. 05) in group C. Safety assessment was done by doing liver and kidney function test at the time of recruitment and end study. Low doses of sodium feredetate (33 mg and 66 mg of elemental iron given twice daily) produce comparable results as higher dose of ferrous fumarate (100 mg elemental iron given twice daily). As there were no adverse effects reported with sodium feredetate, it can be concluded from this study that this new formulation appears to be effective in improving haemoglobin profile in pregnant anaemic women and is tolerated well.