Neonatal outcomes from a randomized controlled trial of maternal treatment of iron deficiency anemia with intravenous ferumoxytol vs oral ferrous sulfate

Abstract

Background: Anemia in pregnancy is common worldwide and has known maternal risks. The relationship between the types of treatment offered for maternal anemia and the effects on the fetus and newborn are largely uninvestigated.

Objective: This study aimed to investigate whether maternal treatment with intravenous ferumoxytol compared to oral ferrous sulfate results in an increase in neonatal hematologic and iron indices. These analyses were planned secondary outcomes and post hoc analysis from the trial with a primary outcome of change in maternal hemoglobin.

Study design: A randomized controlled trial including 124 participants with anemia by World Health Organization criteria was performed in which participants were allocated in a 1:1 ratio to either 2 infusions of 510 mg of intravenous ferumoxytol or 325 mg oral ferrous sulfate twice daily. Fetal monitoring was performed during each intravenous iron infusion. Standard univariable statistical techniques were used to compare groups and to investigate associations between maternal and neonatal hemoglobin and iron indices.

Results: Cord blood hematological parameters were equivalent between groups. Hemoglobin was 15.7 g/dL vs 15.4 g/dL (P=.6) and hematocrit was 50.5% and 49.2% (P=.4) in those randomized to intravenous ferumoxytol and oral ferrous sulfate, respectively. Iron studies revealed higher cord blood ferritin concentrations in infants of participants treated with intravenous ferumoxytol (294 vs 186, P=.005). There were equivalent iron (158 vs 146, P=.4), transferrin (186 vs 196, P=.4) and total iron binding capacity (246 vs 244, P=1) in neonates of participants receiving intravenous vs oral treatment. There were no effects of the infusions observed on cardiotocography. Gestational age at birth was equivalent between groups. We noted a larger birthweight in neonates of participants treated with intravenous ferumoxytol (3215 g vs 3033 g, P=.09), which was not statistically significant. Post hoc analyses revealed a statistically significant correlation between neonatal ferritin and maternal hemoglobin (P=.006) and neonatal ferritin and maternal ferritin (P=.017) at admission for delivery.

Conclusion: Neonates of participants who received intravenous ferumoxytol were born with higher ferritin concentrations in cord blood, at the same gestation with the same birthweight. Participants with higher hemoglobin and ferritin indices delivered infants with higher ferritin concentrations in cord blood.

Trial registration: ClinicalTrials.gov NCT03657433.

Keywords: ferritin; ferumoxytol; intravenous iron infusion; iron-deficiency; neonatal outcomes.