Correction of hemorrhage-induced anemia with intra-amniotic iron in the ovine fetus

OBJECTIVE: This study tested the hypothesis that intra-amniotic iron treatment would enhance fetal red blood cell production after an acute, severe fetal hemorrhage of 40% of estimated blood volume over 2 hours. STUDY DESIGN: Three groups of late-gestation ovine fetuses were studied for 10 days: (1) control fetuses (n = 8), (2) fetuses hemorrhaged on day 3 (n = 11), and (3) similarly hemorrhaged fetuses supplemented with a single bolus of 60 mg of iron injected intra-amniotically immediately after the hemorrhage (n = 7). Statistical analysis was by 3-factor analysis of variance. RESULTS: At 24 hours after hemorrhage, red blood cell mass increased 5% in the control group and was reduced equally in both hemorrhage groups by 32% below day 3 prehemorrhage values. At 7 days after hemorrhage, red blood cell mass increased 27.8% ± 2.6% (SE) above day 3 baseline values in the control fetuses. In the nonsupplemented hemorrhaged fetuses, red blood cell mass was not different from prehemorrhage values after 7 days (±3.7% ± 4.1%), whereas red blood cell mass increased by 29.9% ± 6.1% above prehemorrhage values in the iron-supplemented hemorrhage group (P < .001). CONCLUSION: Intra-amniotic iron supplementation resulted in full restoration of red blood cell mass within 7 days after a large loss of blood in fetal sheep, whereas restoration failed without iron supplementation. Intra-amniotic iron treatment may be of therapeutic value in restoring red blood cell mass in human fetuses with certain types of anemia such as that resulting from fetal or fetomaternal hemorrhage.