The effects of dexamethasone on post-asphyxial cerebral oxygenation in the preterm fetal sheep.

Key points Mothers at risk of preterm delivery are routinely given synthetic glucocorticoids such as dexamethasone to help mature fetal lungs and improve survival after birth. We have previously shown that dexamethasone given after an acute episode of asphyxia in preterm fetal sheep is associated with greater brain injury. In this study we found that fetal exposure to dexamethasone after asphyxia in preterm fetal sheep was associated with reduced intracerebral oxygenation during the critical latent phase of recovery. In the secondary phase, maternal dexamethasone was associated with increased epileptiform transient activity and evidence of greater mitochondrial oxidation. These findings suggest that fetal exposure to the synthetic glucocorticoid dexamethasone is associated with a critical mismatch between the brain's demand for oxygenation and the supply of oxygen that may contribute to greater brain injury. Abstract Exposure to clinical doses of the glucocorticoid dexamethasone increases brain activity and causes seizures in normoxic preterm fetal sheep without causing brain injury. In contrast, the same treatment after asphyxia increased brain injury. We hypothesised that increased injury was in part mediated by a mismatch between oxygen demand and oxygen supply. In preterm fetal sheep at 0.7 gestation we measured cerebral oxygenation using near-infrared spectroscopy, electroencephalographic (EEG) activity, and carotid blood flow (CaBF) from 24 h before until 72 h after asphyxia induced by 25 min of umbilical cord occlusion. Ewes received dexamethasone intramuscularly (12 mg 3 ml–1) or saline 15 min after the end of asphyxia. Fetuses were studied for 3 days after occlusion. During the first 6 h of recovery after asphyxia, dexamethasone treatment was associated with a significantly greater fall in CaBF (P < 0.05), increased carotid vascular resistance (P < 0.001) and a greater fall in cerebral oxygenation as measured by the difference between oxygenated and deoxygenated haemoglobin (delta haemoglobin; P < 0.05). EEG activity was similarly suppressed in both groups. From 6 to 10 h onward, dexamethasone treatment was associated with a return of CaBF to saline control levels, increased EEG power (P < 0.005), greater epileptiform transient activity (P < 0.001), increased oxidised cytochrome oxidase (P < 0.05) and an attenuated increase in [delta haemoglobin] (P < 0.05). In conclusion, dexamethasone treatment after asphyxia is associated with greater hypoperfusion in the critical latent phase, leading to impaired intracerebral oxygenation that may exacerbate neural injury after asphyxia.