Fetal sciatic nerve growth is delayed following repeated maternal injections of corticosteroid in sheep

Abstract

Aims: A single course of prenatal corticosteroid reduces the mortality and morbidity of preterm birth. Repeated courses of prenatal corticosteroids are widely prescribed despite a lack of safety data. Repeated corticosteroids delay myelination in the ovine central nervous system at the time of preterm delivery but with catch-up at term. We aimed to evaluate their effect in the peripheral nervous system.

Methods: Thirty date-mated ewes were administered either saline, a single injection of betamethasone, or four injections of betamethasone between 104 and 124 days' gestation, with delivery on day 125 or 145 (term = 150 days). Sciatic nerves were dissected and fixed in modified Karnovsky's fixative and prepared for light and electron microscopy to determine the proportion of myelinated axons and mean axon diameter.

Results: Repeated, but not single, corticosteroid administration resulted in significant decreases in the total cross-sectional and fascicle-containing areas of the sciatic nerve, and in the mean diameter of myelinated and unmyelinated axons. Deficits persisted at term. The proportion of myelinated axons was unaffected.

Conclusion: Repeated prenatal corticosteroids have the capacity to affect the growth of peripheral nerve axons in sheep. Documentation of their effects in human pregnancy await randomized trials.