Abstract:
Maternal treatment with synthetic corticosteroids such as dexamethasone (DEX) significantly reduces neonatal morbidity and mortality, but its effects on the fetal brain remain unclear. In this study we evaluated the effects of DEX on EEG activity in preterm fetal sheep. Ewes at 103 days gestation received two intramuscular injections of DEX (12 mg, n=8) or saline vehicle (n=7) 24h apart. Fetal EEG activity was recorded from 6h before until 120h after the first injection (DEX-1). DEX-1 was associated with a marked transient rise in total EEG power, maximal at 12h (p<0.001), with a relative increase in delta and reduced theta, alpha, and beta activity, resolving by 24h. Continuous EEG records showed a shift to larger but less frequent transient waveforms (p<0.001). Unexpectedly, evolving epileptiform activity, consistent with electrographic and clinical seizures, developed from 178±44 min after DEX-1. Similar but smaller changes were seen after the second injection. Following the injections, total power returned to control values, but the proportion of alpha activity progressively increased vs. controls (p<0.001), with reduced inter-burst interval duration and number (p<0.001). No histological neural injury or microglial activation was seen. In summary, exposure to maternal dexamethasone was associated with dramatic, evolving low frequency hyperactivity on fetal cortical EEG recordings, followed by sustained changes consistent with maturation of fetal sleep architecture. We postulate that these effects may contribute to improved neonatal outcomes.