Cardiovascular changes: a biomarker for seizures after hypoxia-ischaemia in preterm fetal sheep

Seizures in preterm infants are highly associated with adverse neurodevelopmental outcomes. Clinical diagnosis remains a challenge because seizures in preterm infants are often clinically silent. The present study examined whether seizure-related cardiovascular changes could aid seizure detection. Chronically instrumented preterm fetal sheep at 0.7 gestation received sham hypoxia-ischaemia (HI) (n = 10) or HI induced by 25 min of complete umbilical cord occlusion (n = 10). Fetal electroencephalogram (EEG) recovery and cardiovascular physiology were assessed until 72 h post HI. HI was associated with stereotypic evolving seizure activity starting 14 ± 13 h (mean ± SD) after HI, with an average total seizure count of 42 ± 2, duration 67 ± 25 s, amplitude 187 ± 88 µV, and seizure burden of 150 ± 129 s/h. Individual seizures were associated with increased mean arterial pressure (MAP) (38.2 ± 2.7 to 40.1 ± 3.2 mmHg). The fetal heart rate (FHR) response during seizures was predominantly tachycardia, but either bradycardia or no change was seen in 21% of seizures. Using minute-to-minute variation in MAP and FHR above one standard deviation as thresholds, the presence of seizures on electroencephalogram (EEG) was predicted with a sensitivity of 75.1 ± 30.4% and 66.5 ± 26.2%, respectively. Using MAP and FHR as a composite measure detected 87.1 ± 4.2% of stereotypic seizures. These data suggest that seizure-related transient fluctuations in MAP and FHR are potentially useful biomarkers for electrographic seizure activity.NEW & NOTEWORTHY In preterm fetal sheep, seizures after hypoxia-ischaemia were associated with increased mean arterial pressure and either increased or decreased fetal heart rate. Minute-to-minute variation in mean arterial pressure and fetal heart rate measures detected 75.1 ± 30.4% and 66.5 ± 26.2% of seizures, respectively, whereas together they detected 87.1 ± 4.2%. Assessment of seizure-related cardiovascular changes may help to improve seizure detection in preterm infants.