The effect of intravenous iron supplementation compared to oral iron supplementation during pregnancy on neonatal outcomes-a systematic review of randomized controlled trials.

UNLABELLED: Anemia and iron deficiency during pregnancy have been associated with preterm birth and neonatal complications. However, the evidence on whether intravenous or oral supplementation should be used has been conflicting. The aim was to assess the effectiveness of intravenous iron compared to oral iron supplementation on objective neonatal outcomes. We conducted a systematic review and meta-analysis of randomized controlled trials. Two databases were searched in November 2024 and the search was updated in February 2025. The main outcomes were the rate of preterm birth, stillbirths, and neonatal mortality. Random-effect meta-analysis was used to calculate risk ratios (RR) with 95% confidence intervals (CI). Evidence certainty was assessed according to GRADE. A total of 375 studies were screened and finally 15 were included. Seven studies with 8431 pregnancies analyzed the risk of preterm birth, and the risk appeared to be similar in both groups (RR 0.96, CI 0.86 to 1.07; moderate certainty evidence). Five studies with 8639 pregnancies analyzed the risk of stillbirth and found no difference (RR 0.85, CI 0.64 to 1.13; low certainty evidence). The neonatal mortality rate was 2.0% in the intravenous iron group, and 2.3% in the oral iron group (RR 0.90, CI 0.66 to 1.22; low certainty evidence). Cord hemoglobin levels were comparable between the study groups (mean difference 0.05 g/l, CI -0.33 to 0.24; low certainty evidence), and ferritin levels were slightly higher in the intravenous group (mean difference 19 µg/l, CI 0.5 to 38; low certainty evidence).

CONCLUSIONS

Neonatal clinical outcomes did not differ between intravenous and oral iron supplementation treatment in pregnancy. A higher ferritin level in umbilical cord blood was found in the intravenous iron supplementation group, but the clinical relevance of this difference is unknown. Based on the results of this study, oral iron supplementation is a sufficient way to treat maternal iron deficiency, when focusing on objective neonatal outcomes.

TRIAL REGISTRATION: PROSPERO 2024 CRD42024615533 Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024615533 .

WHAT IS KNOWN: • Iron-deficiency anemia during pregnancy is associated with preterm birth and neonatal complications. • Intravenous iron increases maternal hemoglobin faster than oral iron, but benefits for neonatal outcomes have been unclear.

WHAT IS NEW: • This systematic review and meta-analysis shows that neonatal outcomes-including preterm birth, stillbirth, and mortality-do not differ between intravenous and oral iron supplementation. • Intravenous iron yields higher cord ferritin, but its clinical relevance remains uncertain.