Effects of betamethasone administration to the fetal sheep in late gestation on fetal cerebral blood flow

1. Glucocorticoid administration to women at risk of preterm delivery to ac celerate fetal lung maturation has become standard practice. Antenatal gluc ocorticoids decrease the incidence of intraventricular haemorrhage as well as accelerating fetal lung maturation. Little is known regarding side effec ts on fetal cerebral function. Cortisol and synthetic glucocorticoids such as betamethasone increase fetal blood pressure and femoral vascular resista nce in sheep. 2. 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 instrumen ted fetal sheep at 128 days gestation (term 146 days). The betamethasone in fusion rate was that previously shown to produce fetal plasma betamethasone concentrations similar to human umbilical vein concentrations during anten atal glucocorticoid therapy. 3. Regional CBF was measured in 10 brain regions, using coloured microspher es, 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 mo st pronounced in the thalamus and hindbrain (45-50% decrease) and least pro nounced in the cortical regions (35-40% decrease). It was mediated by an in crease in cerebral vascular resistance (CVR, P < 0.05) and led to a decreas e in oxygen delivery to subcortical and hindbrain structures of 30-40%, to 8.6 +/- 1.1 ml (100 g)(-1) min(-1), and 40-45%, to 11.0 +/- 1.6 ml 100 g(-1 ) min(-1) respectively (P < 0.05). 4. After 48 h of betamethasone treatment, the reduction in CBF was diminish ed to about 25-30%, but was still significant in comparison to vehicle-trea ted fetuses in all brain regions except three of the five measured cortical regions (P < 0.05). CVR and oxygen delivery were unchanged in comparison t o values at 24 h of treatment. The CBF increase in response to hypercapnia was diminished (P < 0.05). 5. These observations demonstrate for the first time that glucocorticoids e xert major vasoconstrictor effects on fetal CBF This mechanism may protect the fetus against intraventricular haemorrhage both at rest and when the fe tus is challenged. Betamethasone exposure decreased the hypercapnia-induced increase in CBF (P < 0.05) due to decreased cerebral vasodilatation (P < 0 .05).