Magnesium sulfate and sex differences in cardiovascular and neural adaptations during normoxia and asphyxia in preterm fetal sheep

Abstract

Magnesium sulfate (MgSO4) is recommended for preterm neuroprotection, preeclampsia, and preterm labor prophylaxis. There is an important, unmet need to carefully test clinical interventions in both sexes. Therefore, we aimed to investigate cardiovascular and neurophysiological adaptations to MgSO4 during normoxia and asphyxia in preterm male and female fetal sheep. Fetuses were instrumented at 98 ± 1 days of gestation (term = 147 days). At 104 days, unanesthetized fetuses were randomly assigned to intravenous MgSO4 ( n = 12 female, 10 male) or saline ( n = 13 female, 10 male). At 105 days fetuses underwent umbilical cord occlusion for up to 25 min. Occlusions were stopped early if mean arterial blood pressure (MAP) fell below 8 mmHg or asystole occurred for >20 s. During normoxia, MgSO4 was associated with similar reductions in fetal heart rate (FHR), EEG power, and movement in both sexes ( P < 0.05 vs. saline controls) and suppression of α- and β-spectral band power in males ( P < 0.05 vs. saline controls). During occlusion, similar FHR and MAP responses occurred in MgSO4-treated males and females compared with saline controls. Recovery of FHR and MAP after release of occlusion was more prolonged in MgSO4-treated males ( P < 0.05 vs. saline controls). During and after occlusion, EEG power was lower in MgSO4-treated females ( P < 0.05 vs. saline controls). In conclusion, MgSO4 infusion was associated with subtle sex-specific effects on EEG spectral power and cardiac responses to asphyxia in utero, possibly reflecting sex-specific differences in interneuronal connectivity and regulation of cardiac output.