Betamethasone effects on fetal sheep cerebral blood flow are not dependent on maturation of cerebrovascular system and pituitary–adrenal axis

Abstract

Synthetic glucocorticoids are administered to pregnant women in premature labour to accelerate fetal lung maturation at a time when fetal cerebrovascular and endocrine systems are maturing. Exposure to glucocorticoids at 0.8-0.9 of gestation increases peripheral and cerebrovascular resistance (CVR) in fetal sheep. We examined whether the increase of CVR and its adverse effect on cerebral blood flow (CBF) depend on the current level of maturation of the pituitary-adrenal axis and the cerebrovascular system. Using fluorescent microspheres, regional CBF was measured in 11 brain regions before and 24 h and 48 h after the start of 3.3 µg kg −1 h −1 betamethasone (n = 8) or vehicle (n = 7) infusions to fetal sheep at 0.73 of gestation. Hypercapnic challenges were performed before and 24 h after the onset of betamethasone exposure to examine betamethasone effects on cerebrovascular reactivity. Betamethasone exposure decreased CBF by approximately 40% in all brain regions after 24 h of infusion (P < 0.05). The decline in CBF was mediated by a CVR increase of 111 ± 16% in the cerebral cortex and 129 ± 29% in subcortical regions (P < 0.05). Hypercapnic cerebral vasodilatation and associated increase in CBF were blunted (P < 0.05). Fetal CBF recovered after 48 h of betamethasone administration. There were no differences in glucocorticoid induced CBF and CVR changes compared with our previous findings at 0.87 of gestation. We conclude that the cerebrovascular effects of antenatal glucocorticoids are independent of cerebrovascular maturation and preparturient increase in activity of the fetal pituitary-adrenal axis.

Postnatal betamethasone vs dexamethasone in premature infants with bronchopulmonary dysplasia: a pilot study

“…We found that delay of weight gain and elevation in blood glucose were less problematic when using betamethasone than dexamethasone whereas effects on clinical lung biology were comparable. Of concern, recent studies have shown a reduction in cerebral blood flow after intravenous betamethasone treatment in both human and sheep newborns; 20,21 we did not observe any increase in the incidence of PVL in infants treated with betamethasone. In fact, we noted a lower incidence of PVL (0 vs 7%) in infants treated with betamethasone than dexamethasone, although this comparison did not achieve statistical significance.…”

“…16 Fifth, importantly, recent studies in sheep and human infants have shown that intravenous betamethasone reduces cerebral blood flow, suggesting its vasoconstrictor effect. 20,21 Thus, betamethasone might affect the incidence of intraventricular hemorrhage and PVL in extremely premature infants.…”

Dexamethasone Alters Vascular Reactivity by Enhancing COX-Related Vasodilatation in Fetal Ovine Carotids

“…Our data also corresponds with clinical investigations performed postnatally which showed increases in cerebral blood fl ow velocity and decreases in resistance index in preterm infants after 60 min of DEX administration [8,23] . In contrast, our fi nding differs from studies performed antenatally, which showed glucocorticoid-induced vasoconstriction after 24, 36, or 48 h of infusion [24,25] , highlighting differences in response between ante-and postnatal corticosteroid administration. As shown in fi gure 2 , we found that continued exposure to DEX for up to 4 h further decreased 5-HT efficacy, consistent with results by Pellicer et al [8] who reported signifi cant increases in cerebral blood fl ow and volume in infants after 4 h of exposure to DEX [8] .…”

Fetal Glucocorticoid Exposure Is Associated with Preadolescent Brain Development

“…Rodent studies have documented that prenatal glucocorticoid exposure affects postnatal brain cell proliferation and levels of glucocorticoid receptor mRNA (84-86). In sheep, antenatal glucocorticoid treatment leads to acute changes in neuronal activity (87, 88), decreased cerebral blood flow (89), disrupted myelination of white matter tracts (90) and decreased brain weight persisting through adulthood (91), with repeated doses having a more profound effect (90, 92). Primate studies provide further evidence for a persisting influence of prenatal glucocorticoid treatment on the brain (93).…”