RESUMEN

We determined the effects of betamethasone on the fetal sheep electrocorticogram (ECoG) using linear (power spectral) and non-linear analysis. For non-linear analysis we used an algorithm based on the Wolf algorithm for the estimation of the leading Lyapunov exponent which calculates a prediction error based on the course of the time series in the phase space. A high prediction error stands for low predictibility or low regularity and vice versa. After 48 h of baseline recordings, vehicle (n = 6) or betamethasone (n = 7) at 10 microg h(-1) was infused over 48 h to the sheep fetus at 128 days gestational age (0.87 of gestation). ECoG spectral analysis revealed no difference in power spectrum between vehicle- and betamethasone-treated fetuses. The prediction error of the ECoG during REM sleep was higher than during non-REM or quiet sleep in both groups (P < 0.0001) revealing lower causality of brain activity during REM sleep. During REM sleep, prediction error significantly decreased 18-24 h after onset of betamethasone treatment (P < 0.05) and returned to baseline values within the following 24 h of continued betamethasone treatment. No ECoG changes were found during quiet sleep. Non-linear ECoG changes during metabolically active REM sleep accompanied the previously described decrease in cerebral blood flow. These results suggest that betamethasone in doses used in perinatal medicine acutely alters complex neuronal activity.

Asunto(s)

RESUMEN

Glucocorticoid administration to women at risk of preterm delivery to accelerate fetal lung maturation has become standard practice. Antenatal glucocorticoids decrease the incidence of intraventricular haemorrhage as well as accelerating fetal lung maturation. Little is known regarding side effects on fetal cerebral function. Cortisol and synthetic glucocorticoids such as betamethasone increase fetal blood pressure and femoral vascular resistance in sheep. We determined the effects of antenatal glucocorticoid administration on cerebral blood flow (CBF) in fetal sheep. Vehicle (n = 8) or betamethasone (n = 8) was infused over 48 h via the jugular vein of chronically instrumented fetal sheep at 128 days gestation (term 146 days). The betamethasone infusion rate was that previously shown to produce fetal plasma betamethasone concentrations similar to human umbilical vein concentrations during antenatal glucocorticoid therapy. Regional CBF was measured in 10 brain regions, using coloured microspheres, before and 24 and 48 h after onset of treatment, and during hypercapnic challenges performed before and 48 h after onset of betamethasone exposure. Betamethasone exposure decreased CBF in all brain regions measured except the hippocampus after 24 h of infusion (P < 0.05). The CBF decrease was most pronounced in the thalamus and hindbrain (45-50% decrease) and least pronounced in the cortical regions (35-40% decrease). It was mediated by an increase in cerebral vascular resistance (CVR, P < 0.05) and led to a decrease in oxygen delivery to subcortical and hindbrain structures of 30-40%, to 8.6 +/- 1.1 ml x (100 g)(-1) x min(-1), and 40-45 %, to 11.0 +/- 1.6 ml x 100 g(-1) x min(-1), respectively (P < 0.05). After 48 h of betamethasone treatment, the reduction in CBF was diminished to about 25-30 %, but was still significant in comparison to vehicle-treated fetuses in all brain regions except three of the five measured cortical regions (P < 0.05). CVR and oxygen delivery were unchanged in comparison to values at 24 h of treatment. The CBF increase in response to hypercapnia was diminished (P < 0.05). These observations demonstrate for the first time that glucocorticoids exert major vasoconstrictor effects on fetal CBF. This mechanism may protect the fetus against intraventricular haemorrhage both at rest and when the fetus is challenged. Betamethasone exposure decreased the hypercapnia-induced increase in CBF (P < 0.05) due to decreased cerebral vasodilatation (P < 0.05).

Asunto(s)

Asunto(s)