Research in context
anaemia, iron deficiency anaemia
ANAEMIA, ANAEMIA IN PREGNANCY, POST-PARTUM HAEMORRHAGE, PREGNANCY COMPLICATIONS, IRON DEFICIENCY ANAEMIA

A search of PubMed for “intravenous iron” AND “pregnancy” OR “antenatal” identified nine systematic reviews, which contained limited trial data available from low-income countries or modern intravenous formulations such as ferric carboxymaltose that enable high-dose iron replacement. The search was from database inception to August, 2022. There were no language restrictions. For example, a systematic review and meta-analysis of 15 trials comparing intravenous iron with oral iron in pregnancy identified advantages from intravenous iron on haematology (intravenous iron therapy led to higher maternal haemoglobin at delivery; mean difference 7·4 g/L [95% CI 3·9–11]; nine RCTs, low-quality evidence) and iron status (ferritin: mean difference 21·2 μg/L [95% CI 6·5–36·0]; three randomised controlled trials [RCTs], low-quality evidence); and low-quality evidence of the benefits on birthweight and need for blood transfusion. A network meta-analysis compared different formulations of iron in pregnancy and identified advantages from intravenous iron over oral formulations of iron in increasing haemoglobin concentration 4 weeks' post-administration (but did not evaluate this outcome before delivery). Older reviews compiled evidence indicating iron sucrose (which can only be given in low doses) provides superior haematologic and iron status outcomes compared with oral iron. We also searched all trials using ferric carboxymaltose in resource-limited settings. Only one trial assessed the use of ferric carboxymaltose in low-income settings: a study in Tanzania recruited 230 randomly assigned post-partum women to oral iron or ferric carboxymaltose and showed that women receiving the intravenous formulation had higher haemoglobin concentrations over a 12-month period. Two RCTs comparing ferric carboxymaltose with oral iron in pregnancy have been conducted: the pivotal FER-ASAP trial recruited 232 pregnant women with iron deficiency anaemia in high-income settings, and showed early superiority from ferric carboxymaltose over high-dose oral ferrous sulphate on haemoglobin concentrations, which was not sustained beyond the first 6 weeks; a smaller trial compared ferric carboxymaltose with oral iron (and intravenous iron polymaltose) in 246 pregnant women and likewise showed more rapid increases in haemoglobin and ferritin in the intravenous groups compared with oral iron. A large trial explored the use of an older intravenous iron formulation (iron sucrose) for iron deficiency anaemia in pregnancy in India: iron sucrose is limited by the low dose that can be delivered in a single infusion, necessitating recurrent visits.
To our knowledge, the randomised trial of intravenous iron for anaemia in Malawian pregnant women (REVAMP) is the first trial to compare a modern intravenous iron formulation capable of rapidly delivering a high dose of iron over a short infusion timeframe to standard of care oral iron to treat antenatal anaemia in a low-income setting, and is also the largest trial to date of ferric carboxymaltose in pregnancy. The trial inclusion criteria were simple and designed to enable translation of results to practice in resource-limited settings. REVAMP recruited a sample size almost times the size of the pivotal FER-ASAP trial. REVAMP shows the feasibility and safety of ferric carboxymaltose in a low-income, primary-care setting where infectious exposures are intense. Our data indicate that compared with oral iron, ferric carboxymaltose markedly reduces iron deficiency anaemia for the duration of pregnancy and into the post-partum, and provides a more rapid elevation in haemoglobin concentration (over oral iron); although this advantage might not be sustained by delivery. Moreover, our data highlight the complex determinants of anaemia in this setting.
Compared with oral iron, ferric carboxymaltose produced a profound reduction in iron deficiency and iron deficiency anaemia, and a more rapid early haematologic response. However, there was no reduction in anaemia prevalence before delivery among the overall cohort; nor did we identify functional benefits from intravenous iron, even though the study population had a high burden of maternal and neonatal pregnancy complications (eg, low birthweight and post-partum haemorrhage). Although the trial was negative for the primary outcome, REVAMP provides new information on urgent technological needs (eg, field-friendly iron status screening), and potential future important contexts for this intervention (women in the third trimester of pregnancy, settings without malaria).Ferric carboxymaltose could present an option to treat anaemia in pregnancy in low-income settings, but the efficacy and safety of this approach in these settings are unproven. We therefore conducted a randomised controlled trial to determine whether a single dose of intravenous ferric carboxymaltose would be superior to standard-of-care (oral iron) in reducing anaemia prevalence at 36 weeks' gestation (before delivery), improve other maternal and neonatal outcomes (including birthweight), and be safe for Malawian women in their second trimester of pregnancy with moderate or severe anaemia (by capillary haemoglobin measurement) and without detectable 