Fetal vascular responses to maternal glucose administration in streptozocin-induced ovine diabetes mellitus

Objective: To assess the impact of administration of a glucose load to the pregnant diabetic ewe on fetal biochemistry and umbilical-placental perfusion. Methods: Six pregnant ewes were rendered glucose intolerant by the administration of streptozocin at 85-90 days gestation. An intravenous glucose load was administered to the 6 diabetic ewes and 4 control animals at 125-130 days gestation. Assessment of the fetal responses to this glucose load was made by cardiovascular monitoring, biochemical evaluation and measurement of fetal blood flows by the radioactive microsphere technique. Results: In the fetus of the diabetic ewe the arterial pH progressively decreased from 7.36 ± 0.04 to 7.10 ± 0.09 (p < 0.05) 180 minutes after the maternal glucose load. These fetuses displayed a consistent and significant reduction in arterial oxygen tension compared to controls, with a decrease in pO₂ from 14.9 ± 3.3 mmHg at baseline to 11.3 + 3.7 mmHg after 180 minutes. Umbilical-placental blood flow did not alter significantly in the fetus of the diabetic ewe following glucose administration, although in the control fetuses there was a significant reduction from baseline after 60 minutes. Blood flow to the fetal brain and kidney were significantly elevated in the fetus of the diabetic ewe compared to control at all times, suggesting a metabolic adaptation to preserve oxygen delivery may be present. Conclusions: Maternal hyperglycemia produces profound metabolic alterations in the ovine fetus which are unaccompanied by significant alterations in umbilical-placental blood flow. In the chronically hyperglycemic pregnant ewe, a glucose load produces a major disturbance of fetal homeostasis.