Antenatal Dexamethasone after Asphyxia Increases Neural Injury in Preterm Fetal Sheep

Background and Purpose: Maternal glucocorticoid treatment for threatened premature delivery dramatically improves neonatal survival and short-term morbidity; however, its effects on neurodevelopmental outcome are variable. We investigated the effect of maternal glucocorticoid exposure after acute asphyxia on injury in the preterm brain. Methods: Chronically instrumented singleton 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 a 3 ml i.m. injection of either dexamethasone (12 mg, n = 10) or saline (n = 10). Sheep were killed after 7 days recovery; survival of neurons in the hippocampus and basal ganglia, and oligodendrocytes in periventricular white matter were assessed using an unbiased stereological approach. Results: Maternal dexamethasone after asphyxia was associated with more severe loss of neurons in the hippocampus (CA3 regions, 290 +/- 76 vs 484 +/- 98 neurons/mm(2), mean +/- SEM, P<0.05) and basal ganglia (putamen, 538 +/- 112 vs 814 +/- 34 neurons/mm(2), P<0.05) compared to asphyxia-saline, and with greater loss of both total (913 +/- 77 vs 1201 +/- 75/mm(2), P<0.05) and immature/mature myelinating oligodendrocytes in periventricular white matter (66 +/- 8 vs 114 +/- 12/mm(2), P<0.05, vs sham controls 165 +/- 10/mm(2), P<0.001). This was associated with transient hyperglycemia (peak 3.5 +/- 0.2 vs. 1.4 +/- 0.2 mmol/L at 6 h, P<0.05) and reduced suppression of EEG power in the first 24 h after occlusion (maximum -1.5 +/- 1.2 dB vs. -5.0 +/- 1.4 dB in saline controls, P<0.01), but later onset and fewer overt seizures. Conclusions: In preterm fetal sheep, exposure to maternal dexamethasone during recovery from asphyxia exacerbated brain damage.