Erythropoietin Elevation in the Chronically Hyperglycemic Fetal Lamb

Abstract

The effects of chronic fetal glucose infusion upon fetal oxygenation and endogenous erythropoietin (Ep) production were studied using the chronically catheterized fetal lamb. Fetal glucose infusion at rates between 5 and 20 mg/kg/min resulted in sustained fetal hyperglycemia. During glucose infusion (maximal glucose concentration achieved = 55.4 ± 3.7 mg/dl) fetal arterial oxygen contents fell from 5.8 ± 0.9 to 4.2 ± 1.0 ml/dl while no changes were observed in simultaneously sampled, noninfused twins. Although plasma insulin concentration rose in the infused fetuses, the elevations were inconstant and no relationship between fetal plasma insulin concentration and decrement in fetal oxygen content was evident. Fetal plasma arterial Ep concentrations in the control state were 13.2 ± 2.8 mU/ml. In infused fetuses, plasma Ep concentrations rose to 150.7 ± 35.9 mU/ml when the fetal arterial oxygen contents fell below 60% of their basal values. A reciprocal relationship was demonstrated between fetal arterial oxygen content and fetal plasma arterial Ep concentration (P < 0.001) in the pooled data of infused fetuses. The changes in plasma Ep concentration were noted prior to any significant fetal metabolic acidosis (as evidence of tissue hypoxia) and no changes in plasma Ep concentration were observed in simultaneously sampled noninfused twins. No relationship was apparent between fetal arterial plasma insulin and Ep concentrations. Since neither fetal anemia nor hemodilution occurred in these preparations, glucose-induced fetal hypoxemia is the likely mechanism behind elevated fetal Ep concentrations in these experiments. Similarities between this animal model and human fetuses and infants of diabetic mothers suggest that chronic in utero hypoxemia may be a common feature responsible for such diverse abnormalities as polycythemia, hyperbilirubinemia, and late fetal demise. The mechanism behind the glucose-induced fetal hypoxemia is not known.