Ferric carboxymaltose for anemia in late pregnancy: a randomized controlled trial

Abstract

Over 46% of African pregnant women are anemic. Oral iron is recommended but often suboptimal, particularly late in pregnancy. Intravenous ferric carboxymaltose (FCM) could treat anemia in women in the third trimester in sub-Saharan Africa. In an open-label, individually randomized trial in antenatal clinics in southern Malawi, we randomized 590 women at 27-35 weeks of gestation with capillary hemoglobin <10.0 g dl^-1 to FCM (20 mg kg^-1 up to 1,000 mg, once at enrollment) or standard of care (60 mg elemental iron, twice daily for 90 days). Participants and their infants were followed to 4 weeks postpartum. Primary outcomes were maternal anemia at 36 weeks' gestation or delivery (whichever occurred first) and neonatal birthweight. At the primary timepoint, 126 of 270 (46.7%) of women in the FCM group were anemic, compared to 170 of 271 (67.3%) women in the standard-of-care group (PR, 0.74 (95% CI 0.64, 0.87); P = 0.0002). There was no difference between groups in birthweight (mean difference 10.9 g (-65.7, 87.5 g); P = 0.78). No serious infusion-related reactions occurred, and there were no differences in adverse events between groups. In Malawian women in late pregnancy, FCM effectively and safely reduced anemia before childbirth. Australia New Zealand Clinical Trial registration: ANZCTR12621001239853.

Fig. 1. Trial profile with an overview of screening, enrollment and follow-up of participants.

Hb, hemoglobin; IV, intravenous; IPTp, intermittent preventative therapy; RDT, rapid diagnostic test. *Reasons for not meeting eligibility criteria were assessed using the questions on the eligibility data collection forms. ‡Reasons for not receiving the treatment were collected on the participant randomization form. §Defined as those who are on IPTp with sulfadoxine–pyrimethamine (SP) at enrollment. Common reasons not to be on IPTp include recent malaria therapy (usually with artemether–lumefantrine) or being HIV positive and receiving cotrimoxazole. ¶A total of 23 randomized women withdrew (this includes the non-pregnant woman) and 10 were lost to-follow-up before delivery, as a result we do not have information on whether they had a live-born baby or not on 18 women in the FCM group and 15 women in the SOC (oral iron) group. In addition, there were 7 stillborn babies. There were 16 twins born in the FCM group and 8 in the SOC (oral iron) group. ||The intention-to-treat basis indicates maternal and neonatal outcomes analyzed according to randomly allocated group of the woman. One woman who was randomized in the SOC (oral iron) but later found to be not pregnant was excluded.

Fig. 2. Subgroup analyses.

a, A PR and 95% CI of FCM versus standard of care (oral iron) is displayed for anemia at 36 weeks’ gestation or at delivery (whichever came first) using a log binomial regression model, including study participants (mothers) as a random intercept to account for multiple time points and adjusting for stratification factor (site). b, An absolute mean difference and 95% CI of venous hemoglobin concentration (g dl⁻¹) change from baseline to 36 weeks’ gestation or delivery (whichever came first) between FCM and standard of care (oral iron) is displayed following fitting a likelihood-based longitudinal data analysis model. c, An absolute mean difference and 95% CI of birthweight (g) between FCM and standard of care (oral iron) is displayed following fitting a linear regression model. d, A PR and 95% CI of FCM versus standard of care (oral iron) is displayed for low birthweight using a log binomial regression model. Birthweight and low birthweight were multiply imputed before analyses. The models in both (a) and (b) include subgroup (main effect) and subgroup-by-treatment-by-visit interactions (and subgroup-by-treatment and subgroup-by-visit interactions) to evaluate how the treatment effect differs between subgroup categories. The models in both (c) and (d) include subgroup (main effect) and subgroup-by-treatment interactions to evaluate how the treatment effect differs between subgroup categories. The intention-to-treat basis indicates outcomes analyzed according to the randomly allocated group of the woman. The 95% CIs presented have not been adjusted for multiple comparisons. The intervals cannot be used in place of hypothesis testing. FCM, ferric carboxymaltose; SOC, standard of care. No statistical analysis was performed due to the small sample size in the subgroup of those with severe anemia at baseline (n = 23).