Iron therapy in iron deficiency anemia in pregnancy: Intravenous route versus oral route

doi:10.1067/mob.2002.121894

American Journal of Obstetrics and Gynecology

Volume 186, Issue 3, March 2002, Pages 518-522

Presented at the 41st Congress of French Anesthesia and Intensive Care Society, Paris, France, September 23-26, 1999.

https://doi.org/10.1067/mob.2002.121894 Get rights and content

Abstract

OBJECTIVE: The aim of this study was to compare intravenous iron sucrose versus oral iron sulfate in anemia at 6 months of pregnancy. STUDY DESIGN: A random, prospective, open study with individual benefit was performed involving 50 patients with hemoglobin levels between 8 and 10 g/dL and a ferritin value of <50 μg/L. In the intravenous group (IV group), the iron dose was calculated from the following formula: Weight before pregnancy (kg) × (120 g/L – Actual hemoglobin [g/L]) × 0.24 + 500 mg. The oral group (PO group) received 240 mg of iron sulfate per day for 4 weeks. Treatment efficacy was assessed by measurement of hemoglobin and reticulocytes on days 8, 15, 21, and 30 and at delivery and of ferritin on day 30 and at delivery. The baby's birth weight and iron stores were noted. Results were expressed as median ± interquartile range. Mann-Whitney and Wilcoxon tests were used for the analysis, with P <.05 considered significant. RESULTS: An increase in hemoglobin was observed, rising from 9.6 ± 0.79 g/dL to 11.11 ± 1.3 g/dL on day 30 in the IV group and from 9.7 ± 0.5 g/dL to 11 ± 1.25 g/dL on day 30 in the PO group (not significant). On day 30 (P <.0001) and at delivery (P =.01) ferritin was higher in the IV group. A mean higher birth weight of 250 g was noted in the IV group (not significant). CONCLUSION: Iron sucrose appears to be a treatment without serious side effects indicated in correction of pregnancy anemia or iron stores depletion. (Am J Obstet Gynecol 2002;186:518-22.)

Section snippets

Material and methods

This random, prospective, open study with individual benefit was supported by the Nancy Regional Maternity Hospital after acceptance by the hospital committee on clinical research. It was approved by the Advisory Committee for Protection of Persons in Biomedical Research at the Nancy Teaching Hospital. Patients' written consent was required. The study took place over a period of 15 months.

The study population consisted of 50 patients >18 years old with a hemoglobin level between 8 and 10 g/dL

Results

The study involved only 47 patients because 3 were excluded during the study. One of these patients, with an initial diagnosis of iron deficiency anemia (ferritin 38 μg/L), was in the intravenous group, but because of ineffectiveness of the treatment on days 8 and 15, despite a sharp increase in ferritin levels, this diagnosis was revised. A hemolytic anemia was suspected and a hematologic advice was solicited. Iron sucrose administration was stopped to prevent accumulation. Two exclusions in

Comment

Iron deficiency anemia during pregnancy is common and deserves special attention because of its potential consequences. Moreover, some pathologic situations increase the risk of hemorrhage and require a rapid restoration of iron reserves. In our study, contrary to results reported by Al-Momen et al⁹ under the same circumstances, iron sucrose does not seem to be more effective than orally administered iron in elevating hemoglobin levels during pregnancy. However, only iron sucrose appears to

Acknowledgements

We thank Dr Tao Lin (Department of Obstetrics and Gynaecology, Maternity Hospital Nancy) for his helpful comments regarding English language corrections. We also thank the hospital committee on clinical research for methodology counseling.

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Cited by (121)

Implementation of a protocol for management of antepartum iron deficiency anemia: a prospective cohort study
2022, American Journal of Obstetrics and Gynecology MFM
Citation Excerpt :
It is critical to effectively treat IDA antepartum to reduce the associated morbidity. Several studies have shown that prenatal iron supplementation improves predelivery Hb and can be safely administered in pregnant women with IDA.11–14 Although oral iron supplementation is often the first choice for the treatment of IDA in pregnancy, the gastrointestinal tract has limited absorptive capacity for iron, and many women are unable to tolerate the gastrointestinal side effects.15
In randomized trials, antepartum intravenous iron sucrose is effective at improving predelivery hemoglobin in iron deficiency anemia. Yet, there is a gap between this knowledge and its implementation into care.
We aimed to determine if the implementation of a standardized protocol for the management of antepartum anemia outside of a clinical trial improves intravenous iron sucrose utilization and clinical outcomes.
We performed a prospective cohort study evaluating the incorporation of an anemia protocol into routine clinical care for women with antepartum hemoglobin <11.0 g/dL. Our protocol, developed with multidisciplinary stakeholders, included (1) serial third trimester hemoglobin assessment, (2) oral iron supplementation for antepartum hemoglobin 9.5–11 g/dL, and (3) antepartum intravenous iron sucrose use (300 mg weekly for 3 weeks) for hemoglobin <9.5 g/dL. We compared 6-months preimplementation (January 2018 to June 2018) to 6-months postimplementation (January 2019 to June 2019). The outcomes evaluated were antepartum intravenous iron sucrose utilization, the number of intravenous iron sucrose dosages, predelivery hemoglobin, and blood transfusion.
A total of 1423 women were included (pre=778; post=645) without significant baseline differences. The antepartum hemoglobin nadir was no different between the groups (pre: 10.2; interquartile range [9.6–10.6] vs post: 10.2; interquartile range [9.6–10.6]; P=.77). The implementation of a standardized protocol for the management of antepartum anemia was associated with 80% increased odds of receiving intravenous iron sucrose than the preimplementation group (pre: 4.8% vs post: 8.2%, P=.008; odds ratio, 1.79; 95% confidence interval, [1.16–2.77]). The implementation of a standardized protocol for the management of antepartum iron deficiency anemia was also associated with higher hemoglobin at admission for delivery (pre: 10.9; interquartile range [10.1–11.6] vs post: 11.0; interquartile range [10.3–11.7], P=.048). There were no significant differences between the groups in blood product transfusion (pre: 7.1% vs post: 5.1%, P=.13).
Implementation of a standardized antepartum anemia protocol is associated with increased intravenous iron sucrose utilization and improvement in predelivery hemoglobin.
Iron preparations for women of reproductive age with iron deficiency anaemia in pregnancy (FRIDA): a systematic review and network meta-analysis
2021, The Lancet Haematology
Citation Excerpt :
The total daily dose of elemental iron across the trials of oral preparations ranged from 60 mg50 to 240 mg,13 with the majority of dosages being between 100 mg and 200 mg (appendix pp 23–29). Of all included trials, 30 (62 groups; 3243 women) reported on haemoglobin at 4 weeks from baseline and were included in the network meta-analysis for haemoglobin (table).13,16,31,33,36,47,48,50,58–79 These 30 trials compared 15 different interventions: nine oral iron preparations, three intravenous preparations, one intramuscular preparation, lactoferrin, and one non-iron intervention (figure 2A).
Numerous iron preparations are available for the treatment of iron deficiency anaemia in pregnancy. We aimed to provide a summary of the effectiveness and safety of iron preparations used in this setting.
We did a systematic review and network meta-analysis of randomised trials. We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, trial registers, and grey literature for trials published in any language from Jan 1, 2011, to Feb 28, 2021. We included trials including pregnant women with iron deficiency anaemia and evaluating iron preparations, irrespective of administration route, with at least 60 mg of elemental iron, in comparison with another iron or non-iron preparation. Three authors independently selected studies, extracted data, and did a risk of bias assessment using the Cochrane tool (version 1.0). The primary outcome was the effectiveness of iron preparations, evaluated by changes in haemoglobin concentration at 4 weeks from baseline. The secondary outcomes were change in serum ferritin concentration at 4 weeks from baseline and treatment-related severe and non-severe adverse events. We did random-effects pairwise and network meta-analyses. Side-effects were reported descriptively for each trial. This study is registered with PROSPERO, CRD42018100822.
Among 3037 records screened, 128 full-text articles were further assessed for eligibility. Of the 53 eligible trials (reporting on 9145 women), 30 (15 interventions; 3243 women) contributed data to the network meta-analysis for haemoglobin and 15 (nine interventions; 1396 women) for serum ferritin. The risk of bias varied across the trials contributing to network meta-analysis, with 22 of 30 trials in the network meta-analysis for haemoglobin judged to have a high or medium global risk of bias. Compared with oral ferrous sulfate, intravenous iron sucrose improved both haemoglobin (mean difference 7·17 g/L, 95% CI 2·62–11·73; seven trials) and serum ferritin (mean difference 49·66 μg/L, 13·63–85·69; four trials), and intravenous ferric carboxymaltose improved haemoglobin (mean difference 8·52 g/L, 0·51–16·53; one trial). The evidence for other interventions compared with ferrous sulfate was insufficient. The most common side-effects with oral iron preparations were gastrointestinal effects (nausea, vomiting, and altered bowel movements). Side-effects were less common with parenteral iron preparations, although these included local pain, skin irratation, and, on rare occasions, allergic reactions.
Iron preparations for treatment of iron deficiency anaemia in pregnancy vary in effectiveness, with good evidence of benefit for intravenous iron sucrose and some evidence for intravenous ferric carboxymaltose. Clinicians and policy makers should consider the effectiveness of individual preparations before administration, to ensure effective treatment.
None.
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
2019, The Lancet Global Health
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.
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.
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.
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.
WHO, India.
Intravenous ferric carboxymaltose for the treatment of iron deficiency anemia: Letter to Editor
2020, Hematology, Transfusion and Cell Therapy
Cost-effectiveness analysis of parenteral iron therapy compared to oral iron supplements in managing iron deficiency anemia among pregnant women
2024, Health Economics Review
Clinical outcome post treatment of anemia in pregnancy with intravenous versus oral iron therapy: a systematic review and meta-analysis
2024, Scientific Reports

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^☆: Supported by Maternity Hospital Nancy.

^☆☆: Reprint requests: Françoise Bayoumeu, MD, Anesthesia and Intensive Care Department, Regional Maternity Hospital, rue du Dr Heydendreich, B.P. 4213, F-54042 Nancy Cedex, France.

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General Obstetrics and Gynecology: ObstetricsIron therapy in iron deficiency anemia in pregnancy: Intravenous route versus oral route☆,☆☆

Abstract

Section snippets

Material and methods

Results

Comment

Acknowledgements

Am J Obstet Gynecol

Eur J Obstet Gynecol Reprod Biol

Am J Clin Nutr

Am J Obstet Gynecol

Am J Kidney Dis

Epidemiology of iron deficiency and iron deficiency anemia in the French population

Ann Biol Clin

Red cell use during cesarean delivery

Transfusion

Autologous blood transfusions and pregnancy

Obstet Gynecol

Autologous predeposit blood donation in pregnancy: a perspective

Aust N Z J Obstet Gynaecol

Use of recombinant human erythropoietin (EPO-alfa) in a mother alloimmunized to the Js(b) antigen

J Matern Fetal Med

General Obstetrics and Gynecology: Obstetrics
Iron therapy in iron deficiency anemia in pregnancy: Intravenous route versus oral route☆,☆☆