Safety and Efficacy of Rapid (one hour) Single Intravenous Dose Low Molecular Weight Iron Dextran for Treatment of Oral Iron Intolerant Maternal Iron Deficient Anemia

OBJECTIVE:  Determine safety and efficacy of rapid (one hour) intravenous infusion of 1,000 mg low molecular weight iron dextran to pregnant women with moderate to severe iron deficient anemia.

INTRODUCTION: Up to 70% of pregnant women to whom oral iron is prescribed report significant gastrointestinal side effects.  Intravenous iron is an efficient, but often overlooked, therapeutic alternative.

METHODS:   We conducted an observational treatment study of 1000 mg low molecular weight iron dextran for moderate to severe iron deficient anemia of pregnancy in 189 consecutive, unselected second and third trimester gravidas intolerant of, or unresponsive to, oral iron.   All received an intravenous test dose of approximately 25 mg low molecular weight iron dextran.  They were then monitored closely for adverse reactions during the balance of a 60 minute infusion.  No premedication was administered unless two or more drug allergies or asthma was present in which case prophylactic intravenous methylprednisolone was administered.  All subjects were followed through pregnancy and delivery.   Monitored parameters included hemoglobin (Hgb), mean corpuscular volume (MCV), serum ferritin, and percent transferrin saturation.

RESULTS:  One hundred eighty-nine subjects received a single intravenous dose of 1000 mg low molecular weight iron dextran.  No first trimester gravidas were treated.  No serious adverse events occurred.  Minor, self-limited infusion reactions (myalgias or flushing), occurred in 2% of subjects.  The mean number of days from treatment to delivery was 58.6 (range 5-190) days.  The change in Hgb was positively correlated with the time from treatment to delivery (r²=0.17, p=0.0039).  The initial Hgb was 10.1 g/dl (SD 1.03, SE 0.07) and at delivery 11.5 g/dl (SD=1.04, SE 0.10), with the mean change from diagnosis to delivery of 1.39 g/dl (p<0.0001). An improvement in Hgb was observed in 174 (92% (Figure 1)).  In 110 (58%) the observed increment was 1.00-1.99 g/dl (hemoglobin response) and in 45 (24%) ≥ 2.00 g/dl (hematopoietic response).  Second trimester treatment was not associated with a greater improvement in Hgb than third trimester treatment.  MCV increased by 3.27 femtoliters (fl) for those treated in the second (p<0.0001), and 1.34 in the third (p<0.0001). The mean increment in MCV for those treated in the second trimester was 1.93 fl higher than those treated in the third (p=0.02).  Post-partum data were available on 64 (34%).  For this subgroup the mean change in Hgb from diagnosis to delivery was 1.48 g/dl, not significantly different than the observed increment for the entire group of 189.  From delivery to post-partum follow-up, an additional Hgb increment of 0.66 g/dl was observed (p<0.0001) consistent with sustained iron repletion and post-partum contraction of plasma volume.  The increment in Hgb from diagnosis to delivery and diagnosis to post-partum was similar irrespective of trimester of treatment.  Anemia resolved in 95%. 

CONCLUSION:   Administration of a rapid (one hour) single large dose (1000 mg) of intravenous low molecular weight iron dextran is a convenient, effective, well tolerated and safe treatment for maternal iron deficient anemia in women who are intolerant of, or unresponsive to, oral iron.   These data are relevant in light of recent publications reporting iron deficient neonates have both delayed growth and development and a statistically significant increment in both cognitive and behavioral abnormalities persisting up to ten years after iron repletion. 

Figure 1. Change in mean hemoglobin concentration (g/dL) +/- SE from diagnosis to delivery to postpartum follow up.