Postpartum maternal and infant haematological effects of second-trimester ferric carboxymaltose versus standard-of-care oral iron in Malawi: longitudinal follow-up of a randomised controlled trial

Abstract

Background: Anaemia is common in mothers and infants in the first year postpartum, especially in sub-Saharan Africa. We evaluated whether treating anaemia in the second trimester of pregnancy with a single dose of intravenous iron, ferric carboxymaltose, compared with standard-of-care oral iron could alleviate anaemia in postpartum women and their infants.

Methods: REVAMP (ACTRN12618001268235), an open-label, individually randomised, controlled trial done across nine urban and five rural health centres in Malawi, recruited women if they were in the second trimester of singleton pregnancy, had a capillary haemoglobin concentration of less than 10·0 g/dL, and had a negative malaria rapid diagnostic test. Once enrolled, women were randomly assigned (1:1) to receive intravenous ferric carboxymaltose (20 mg/kg up to 1000 mg) or standard of care (60 mg oral elemental iron twice daily for 90 days); all women received preventive malaria treatment. The primary endpoint of REVAMP was anaemia prevalence at 36 weeks of gestation, with follow-up of mothers and infants until 1 month postpartum. In REVAMP-EXTENDED, women from REVAMP who gave consent, and their infants, were followed up at 3, 6, 9, and 12 months postpartum, and venous blood was collected for haemoglobin, ferritin, and C-reactive protein measurement. Maternal postpartum outcomes comprised prevalence of anaemia (venous haemoglobin concentration <11 g/dL up to and including delivery and <12·0 g/dL postpartum) and haemoglobin concentration, as well as iron status (iron deficiency, defined as serum ferritin <15 μg/L, or <30 μg/L if C-reactive protein >5 mg/L, and iron deficiency anaemia [both iron deficiency and anaemia]). Infant outcomes comprised cord ferritin concentration, and haemoglobin and ferritin concentrations at 1, 3, 6, 9, and 12 months of age.

Findings: Between Nov 12, 2018, and March 2, 2021, 862 women were randomly assigned in REVAMP, of whom 793 (393 in the ferric carboxymaltose group [376 liveborn infants] and 400 [379 liveborn infants] in the standard-of-care group) provided consent for REVAMP-EXTENDED. At 12 months postpartum, ferritin concentrations were higher (geometric mean ratio 1·47 [95% CI 1·29-1·66], p<0·0001), and prevalence of iron deficiency was lower (prevalence ratio 0·65 [0·48-0·88], p=0·0050), in mothers receiving ferric carboxymaltose than in those receiving standard of care. Anaemia was less common in women who received ferric carboxymaltose than in those who received standard of care at 1 month (prevalence ratio 0·84 [95% CI 0·71-0·98], p=0·027), 3 months (0·75 [0·62-0·91], p=0·0029), and 6 months (0·78 [0·63-0·96], p=0·018) postpartum but not thereafter. There was no evidence of a difference between groups regarding cord ferritin, infant ferritin, or infant haemoglobin concentrations at any timepoint. Benefits on postpartum anaemia were restricted to mothers with baseline iron deficiency.

Interpretation: Ferric carboxymaltose treatment in the second trimester protected women from postpartum anaemia and iron deficiency but did not affect infant haematological or iron status.

Funding: Bill & Melinda Gates Foundation.

Translation: For the Chichewa translation of the abstract see Supplementary Materials section.

Figure 1

Maternal outcomes by maternal iron deficiency status at baseline Anaemia is defined as venous haemoglobin less than 11·0 g/dL up to and including delivery and venous haemoglobin less than 12·0 g/dL postpartum. Iron deficiency is defined as serum ferritin less than 15 μg/L, or less than 30 μg/L if C-reactive protein is higher than 5 mg/L. Iron deficiency anaemia indicates venous haemoglobin less than 11g/dL up to and including delivery and serum ferritin less than 15 μg/L, or serum ferritin less than 30 μg/L if C-reactive protein is higher than 5 mg/L. A prevalence ratio (error bars indicate 95% CIs) of ferric carboxymaltose versus standard of care is plotted for maternal anaemia, iron deficiency, and iron deficiency anaemia at 1, 3, 6, 9, and 12 months postpartum.

Figure 2

Maternal and infant outcomes by maternal iron deficiency status at baseline (A) Maternal and infant venous haemoglobin. An absolute mean difference (error bars indicate 95% CIs) of ferric carboxymaltose versus standard of care of the estimated change from baseline to 1, 3, 6, 9, and 12 months postpartum is plotted for maternal and infant haemoglobin following analyses using a longitudinal data analysis model. (B) Maternal and infant serum ferritin. A geometric mean ratio (error bars indicate 95% CIs) is displayed for maternal and infant log-transformed ferritin concentration. Anaemia is defined as venous haemoglobin less than 11·0 g/dL up to and including delivery and venous haemoglobin less than 12·0 g/dL postpartum. Iron deficiency is defined as serum ferritin less than 15 μg/L, or less than 30 μg/L if C-reactive protein is higher than 5 mg/L. Iron deficiency anaemia is defined as venous haemoglobin less than 11g/dL up to and including delivery and serum ferritin less than 15 μg/L, or serum ferritin less than 30 μg/L if C-reactive protein is higher than 5 mg/L.