We evaluated the effect of
magnesium sulphate (MgSO4 ) on
seizures induced by
asphyxia in preterm fetal sheep. MgSO4 did not prevent
seizures, but significantly reduced the total duration, number of
seizures, seizure amplitude and average seizure burden. Saline-
asphyxia male fetuses had significantly more
seizures than female fetuses, but male fetuses showed significantly greater reduction in
seizures during MgSO4 infusion than female fetuses. A circadian profile of seizure activity was observed in all fetuses, with peak
seizures seen around 04.00-06.00 h on the first and second days after the end of
asphyxia. This study is the first to demonstrate that MgSO4 has utility as an anti-seizure agent after
hypoxia-ischaemia. More information is needed about the mechanisms mediating the effect of MgSO4 on
seizures and sexual dimorphism, and the influence of circadian rhythms on seizure expression.
ABSTRACT:
Seizures are common in newborns after
asphyxia at birth and are often refractory to anti-seizure agents.
Magnesium sulphate (MgSO4 ) has
anticonvulsant effects and is increasingly given to women in preterm labour for potential neuroprotection. There is limited information on its effects on perinatal
seizures. We examined the hypothesis that MgSO4 infusion would reduce fetal
seizures after
asphyxia in utero. Preterm fetal sheep at 0.7 gestation (104 days, term = 147 days) were given
intravenous infusions of either saline (n = 14) or MgSO4 (n = 12, 160 mg bolus + 48 mg h-1 infusion over 48 h). Fetuses underwent umbilical cord occlusion (UCO) for 25 min, 24 h after the start of infusion. The start time for
seizures did not differ between groups, but MgSO4 significantly reduced the total number of
seizures (P < 0.001), peak seizure amplitude (P < 0.05) and seizure burden (P < 0.005). Within the saline-
asphyxia group, male fetuses had significantly more
seizures than females (P < 0.05). Within the MgSO4 -
asphyxia group, although both sexes had fewer
seizures than the saline-
asphyxia group, the greatest effect of MgSO4 was on male fetuses, with reduced numbers of
seizures (P < 0.001) and seizure burden (P < 0.005). Only 1 out of 6 MgSO4 males had
seizures on the second day post-UCO compared to 5 out of 6 MgSO4 female fetuses (P = 0.08). Finally,
seizures showed a circadian profile with peak
seizures between 04.00 and 06.00 h on the first and second day post-UCO. Collectively, these results suggest that MgSO4 may have utility in treating perinatal
seizures and has sexually dimorphic effects.