Erythropoietin in Human Fetuses With Immune Hemolytic Anemia and Hydrops Fetalis

OBJECTIVE:To determine whether plasma erythropoietin is increased in fetuses with anemia due to Rh isoimmunization. METHODS:Hemoglobin and erythropoietin were measured in samples obtained by funipuncture from 15 fetuses with Rh isoimmunization (gestational age 26.2 ± 5.0 weeks, mean ± standard deviation) and from 13 control fetuses (23.1 ± 6.7 weeks). Hemoglobin and erythropoietin also were determined in umbilical cord blood collected at birth from 20 term fetuses delivered by elective cesarean. RESULTS:Fetuses with Rh isoimmunization had lower hemoglobin and higher plasma erythropoietin measurements than mid-gestation controls (6.1 ± 3.9 versus 10.7 ± 1.5 g/dL and 105.5 ± 168.1 versus 12.5 ± 3.1 mU/mL, P < .05, respectively). Hemoglobin and plasma erythropoietin increased with gestational age in control fetuses. There was an inverse association between hemoglobin and plasma erythropoietin in control and Rh-isoimmunized fetuses (r=—0.56, P < .005). Using multiple linear regression, hemoglobin and gestational age were associated independently with plasma erythropoietin (overall F2,25=12.3, multiple r=0.49, P < .001). Despite marked decreases in hemoglobin, fetuses below 24 weeksʼ gestation had minimal increases in plasma erythropoietin compared to fetuses above that gestational age. Mildly anemic Rh-isoimmunized fetuses (hemoglobin 11.6 ± 2.0 g/dL) delivered vaginally had significantly higher erythropoietin levels in umbilical cord plasma than Rh-isoimmunized fetuses with comparable hemoglobin (10.9 ± 3.5 g/dL) delivered by elective cesarean without labor (1246 ± 856 versus 106 ± 66 mU/mL, respectively, P < .05). CONCLUSION:Fetuses with anemia at mid to late gestation respond with increases in plasma erythropoietin, but these changes are substantially attenuated before 24 weeksʼ gestation.