The consequences of antenatal glucocorticoids during and after asphyxia in the preterm fetus

Abstract

Introduction: Fetuses at risk of premature delivery are now routinely exposed to maternal treatment with synthetic glucocorticoids. Despite their widespread use, there is little knowledge of how these steroids interact with common insults in utero such as asphyxia. This study aimed to evaluate whether glucocorticoids given before severe asphyxia would reduce injury, through improved cardiovascular support during the primary insult and increased metabolic support during the recovery period. Methods: Chronically instrumented preterm fetal sheep at 0.7 gestation were exposed to maternal intramuscular injection of 12 mg dexamethasone, or saline, 4 hours before a 25 minute complete umbilical cord occlusion (asphyxia), or sham asphyxia. The groups studied were sham asphyxia + saline (n=8), asphyxia + saline (n=12), sham asphyxia + saline (n=12), and asphyxia + dexamethasone (n=7). Continuous monitoring was carried out for seven days, and then brains were taken at post mortem for histological analysis. Results: Asphyxia + dexamethasone fetuses had higher CaBF from 5-10 minutes occlusion (P<0.05), and a significantly attenuated rise in impedance compared to the asphyxia + saline group from 11-24 minutes of occlusion (P<0.05). During early recovery, CaBF was significantly lower in the asphyxia + dexamethasone group versus asphyxia + saline group from 2-8 hours, when EEG amplitude was markedly higher (P<0.05). EEG spectral edge was suppressed in the asphyxia + dexamethasone group compared to all other groups from 52 hours until the end of the experiment, with a striking exacerbation of seizure activity. There was a profound increase in impedance in the asphyxia + dexamethasone group from 22-47 hours, followed by a significant drop below baseline levels (P<0.05). Histological analysis showed a significant reduction in neuron, and immature oligodendrocyte number and significantly increased microglia in the asphyxia + dexamethasone group (P<0.05). Conclusion Dexamethasone markedly altered the fetal adaptations to, and recovery from asphyxia resulting in a profound exacerbation of neural injury. Fetuses appeared to adapt better during the primary insult, with injury likely having been exacerbated during the latent and secondary phases of recovery.