Among 1,715 pregnant Pakistani women with haemoglobin below 10 g/dL, intravenous iron administered within 14 days of anaemia identification reduced the risk of moderate-to-severe anaemia by 60% (pooled RR 0.40; 95% CI: 0.27–0.59). More strikingly, IV iron was associated with an 83% reduction in stillbirth risk (95% CI: 55–94%), with similar directional trends for perinatal and neonatal mortality across five gestational-age windows — findings derived using target trial emulation methodology on observational antenatal care data.
Anaemia in pregnancy, affecting roughly 40% of pregnant women globally and disproportionately burdening South Asia, is mechanistically linked to fetal hypoxia, growth restriction, and placental insufficiency — plausible pathways connecting iron repletion to improved fetal survival. While oral iron remains first-line treatment, IV formulations bypass intestinal absorption barriers that reduce efficacy in moderate-to-severe deficiency. The magnitude of the stillbirth effect here is remarkable, even exceeding gains seen in some randomised trials of oral supplementation, raising important questions about timing and route of administration.
Critical caveats apply. This is an observational study using target trial emulation — a rigorous causal inference framework, but one that cannot fully eliminate unmeasured confounding. The 83% stillbirth reduction, while biologically plausible, should be interpreted cautiously given relatively small event counts. Crucially, this is a preprint not yet peer-reviewed, and effect estimates may shift substantially following independent scrutiny. Confirmatory randomised evidence is urgently needed before clinical guidelines are revised.