Temporal changes in fetal cardiovascular, behavioural, metabolic and endocrine responses to maternally administered dexamethasone in the late gestation fetal sheep.

Abstract

To determine the primary (0-12 h) and secondary (12-24 h) effects of dexamethasone on fetal heart rate, short term heart rate variation, blood pressure, breathing movements and electrocortical activity, blood gas exchange, metabolism and adrenocortical function in the late gestation sheep fetus. Comparison of the effects of a single maternally administered intramuscular injection of dexamethasone (12 mg) with those of saline vehicle from 1 h before injection to 24 h post-injection. Fetal cardiovascular and behavioural parameters were recorded continuously. Fetal and maternal blood samples were taken at regular intervals for blood gas, glucose and lactate, cortisol and adrenocorticotrophin measurements. Sixteen chronically instrumented singleton fetal sheep at 127-133 days of gestation (term is about 147 days). During the primary phase short term heart rate variation fell (P < 0.001), and this was associated with a transient fall in the incidence of fetal breathing movements, a fall in fetal heart rate and a rise in fetal blood pressure. By 12 h there was a significant increase in short term heart rate variation (P < 0.001) and a rise in fetal heart rate, but blood pressure and fetal breathing movements had returned to normal. Dexamethasone significantly reduced fetal PaO2 throughout most of the experimental period, particularly 1 h post-injection (P < 0.005). Fetal and maternal plasma cortisol and adrenocorticotrophin concentrations fell significantly from 1 h post-injection. The effects of dexamethasone on fetal heart rate variation are more complex than previously described with both a fall and an increase observed depending on the time at which heart rate variation was measured after injection. Dexamethasone also caused a significant fall in fetal PaO2, and although this was not to hypoxic levels in normoxic fetuses it does raise questions about the potential impact of dexamethasone on chronically hypoxic fetuses.