Intravenous iron for non-anaemic iron deficiency in pregnancy: a multicentre, two-arm, randomised controlled trial

BACKGROUND: In non-anaemic iron deficiency during pregnancy, it remains unclear whether the administration of intravenous iron improves maternal and infant outcomes, compared with prophylactic oral iron that is currently recommended for antenatal care. This study evaluated whether the addition of intravenous iron to routine oral prophylaxis had an effect on maternal haemoglobin concentration before delivery in non-anaemic iron deficient pregnant women.

METHODS: In this multicentre, two-arm, randomised trial done at three teaching hospitals in Lahore, Pakistan, pregnant women aged 18 years or older with a singleton pregnancy were screened at the first antenatal care booking visit for non-anaemic iron deficiency (haemoglobin 11-13 g/dL at booking with ferritin <30 μg/L). Women with high haemoglobin concentrations were excluded. Participants were randomly assigned (1:1) to an intervention during the second trimester using serially numbered, opaque, identical boxes, prepared by a third party using computer-generated random numbers with variable block sizes. Participants were assigned to either receive 1000 mg of intravenous iron in addition to routine oral iron prophylaxis, or to receive prophylactic 30 mg oral iron daily as the standard of routine care throughout pregnancy. Outcome assessors were masked to group allocation. Participants were followed up to delivery. The primary outcome was the mean change in maternal haemoglobin concentration from baseline to 36 weeks' gestation. We performed the primary analysis applying the intention-to-treat principle in all randomly assigned participants who had data for the primary outcome available (full analysis set). We assessed participants for serious or life-threatening adverse events such as death, cardiac arrest, myocardial infarction, anaphylactic shock, and reactions leading to intensive care admission and discontinuation of treatment. The trial is registered at ClinicalTrials.gov number, NCT04228627, and is completed.

FINDINGS: Between Jan 14, 2020, to Aug 29, 2023, 1206 women were screened for eligibility, 606 were ineligible for participation due to reasons including age, gestational age, and haemoglobin concentration, and 600 were enrolled in the study. 295 women were assigned to the intravenous iron group and 305 were assigned to the oral iron prophylaxis group, and all were followed up until delivery. 228 women delivered in the intravenous iron group (14 preterm), and 234 women delivered in the oral iron prophylaxis group (21 preterm; three without primary outcome data). Maternal haemoglobin concentration before delivery was 11·6 g/dL (SD 0·5) in the intravenous iron group and 10·8 g/dL (0·7) in the prophylactic oral iron group (mean difference, 0·74 g/dL [95% CI 0·64-0·85]; p<0·0001). None of the participants experienced serious or life-threatening adverse events.

INTERPRETATION: Among non-anaemic iron deficient pregnant women, intravenous iron therapy significantly improved maternal haemoglobin before delivery, compared with oral iron prophylaxis. Ferritin screening should be considered in early pregnancy, as intravenous iron therapy is effective in those tested positive for non-anaemic deficiency.

FUNDING: None.