Repeated, but not single, maternal administration of corticosteroids delays myelination in the brain of fetal sheep

Objectives A single maternal course of corticosteroids reduces the mortalit y and morbidity of preterm birth. The prescription of repeated courses of m aternally administered corticosteroids is widespread in clinical practice d espite a lack of randomized controlled trials on their efficacy or safety. We examined the effect of single and repeated maternal injections of betame thasone on the maturation of the ovine optic nerve. Methods Forty six date-mated ewes were administered either saline, a single injection of betamethasone, or four injections of betamethasone between 10 4 and 124 days' gestation, with delivery on day 125 or day 145 (term = 150 days). Head and neck were perfused and tissue prepared for light and electr onmicroscopy to determine optic axon numbers and the proportion of myelinat ed axons. Results Repeated, but not single, corticosteroid administration resulted in significant reductions in myelination at 125 days (p < 0.0001). By 145 day s, myelination had recovered. Axon numbers were not affected. Conclusion In light of trends in clinical practice, our findings indicate t hat further work is required to evaluate the potential benefits and harm of prescribing repeated maternal doses of corticosteroids in human pregnancy.