Repeated ultrasound guided fetal injections of corticosteroid alter nervous system maturation in the ovine fetus

Abstract

Introduction: Recent studies in sheep have shown that repeated maternal injections of betamethasone are associated with adverse effects within the nervous system. Repeated fetal injections of betamethasone achieve serial improvements in preterm lung function in sheep and are a possible alternative to repeated maternal therapy. We have evaluated the effect of repeated fetal administration of betamethasone on nervous system maturation in an ovine model.

Methods: Date-mated ewes (n = 48) were randomized to receive ultrasound-guided fetal injections of betamethasone or saline between days 104 to 124 of gestation and were delivered by cesarean section on day 125 or 145 (term = 150). Optic and sciatic nerves were prepared for light and electronmicroscopy. Eye diameters were measured and transverse sections of retinae were evaluated. Data were analyzed using a mixed model analysis of variance.

Results: Repeated fetal administration of corticosteroid did not significantly affect optic nerve myelination but resulted in significant delays in sciatic axonal growth (p < 0.02) and retinal maturation (p < 0.04). The process of performing repeated fetal injections also significantly affected some retinal parameters.

Conclusion: Repeated fetal administration of betamethasone alters some aspects of nervous system maturation in sheep. It is premature to plan trials of repeated fetal corticosteroid therapy in humans.