The Fetal and Neonatal Workshop of Australia and New Zealand

Exposure to maternal glucocorticoids exacerbates post-asphyxial brain injury in the preterm fetus Miriam Koome, Paul P Drury, Joanne O Davidson, Sam Mathai, Sherly George, Alistair J Gunn, & Laura Bennet 1 Department of Physiology, University of Auckland, Auckland, New Zealand [email protected] Background: maternal glucocorticoid treatment for threatened premature delivery consistently improves survival and short-term morbidity; however, its effects on neurodevelopmental outcome are rather variable. In sheep, maternal dexamethasone leads to dramatic, evolving hyperactivity in the preterm fetus, raising the possibility that dexamethasone may adversely affect neural suppression which is an important protective response to hypoxic-ischaemic injury. Aims/Hypothesis: We tested the hypothesis that maternal glucocorticoid exposure could sensitise the preterm brain to asphyxia-induced injury. Methods: chronically instrumented fetal sheep at 0.7 of gestation received asphyxia induced by complete umbilical cord occlusion for 25 minutes. 15 minutes after release of occlusion, ewes received an i.m. injection of either dexamethasone (12 mg in 3 mL saline, n=6) or saline (n = 7). Sheep were killed 7 days later for histology. Results: Maternal dexamethasone was associated with transient hyperglycaemia (peak 3.5±0.2 vs 1.40.2mmol/L at 6 h), reduced suppression of the EEG activity in the first 24 h after occlusion (maximum recovery -1.5 ± 1.2 dB vs -5.0 ± 1.4 dB in controls, p<0.01), with increased epileptiform transient activity on the continuous EEG recordings (peak: 31 ± 8 % of activity vs 13 ± 5 %). This was associated with significant increased in neuronal loss in the hippocampus (CA1/2: 51 vs 1.11.1, CA3 3512 VS 136.3). Conclusions: these data strongly suggest that maternal dexamethasone therapy has potential to moderately exacerbate brain damage in an already compromised fetus. The precise mechanisms are unknown but may include fetal hyperglycaemia and loss of postasphyxial metabolic suppression. 1. Davidson JO, Quaedackers JS, George SA, Gunn AJ, Bennet L. Maternal dexamethasone and EEG hyperactivity in preterm fetal sheep. J Physiol 589(15):3823–3835, 2011.