Transient effects of forebrain ischemia on fetal heart rate variability in fetal sheep

Abstract

Fetal heart rate variability (FHRV) is a key index of antenatal and intrapartum fetal well-being. FHRV is well established to be mediated by both arms of the autonomic nervous system, but it remains unknown whether higher centers in the forebrain contribute to FHRV. We tested the hypothesis that selective forebrain ischemia would impair the generation of FHRV. Sixteen chronically instrumented near-term fetal sheep were subjected to either forebrain ischemia induced by bilateral carotid occlusion or sham-ischemia for 30 min. Time, frequency, and nonlinear measures of FHRV were assessed during and for seven days after ischemia. Ischemia was associated with profound suppression of electroencephalographic (EEG) power, which remained suppressed throughout the recovery period ( P < 0.001). During the first 5 min of ischemia, multiple time and frequency domain measures were increased (all P < 0.05) before returning back to sham levels. A delayed increase in sample entropy was observed during ischemia ( P < 0.05). For the first 3 h after ischemia, there was moderate suppression of two measures of FHRV (very-low frequency power and the standard deviation of RR-intervals, both P < 0.05) and increased sample entropy ( P < 0.05). Thereafter, all measures of FHRV returned to control levels. In conclusion, profound forebrain ischemia sufficient to lead to severe neural injury had only transient effect on multiple measures of FHRV. These findings suggest that the forebrain makes a limited contribution to FHRV. FHRV therefore primarily originates in the hindbrain and is unlikely to provide meaningful information on forebrain neurodevelopment or metabolism.

Fetal heart rate variability is a biomarker of rapid but not progressive exacerbation of inflammation in preterm fetal sheep

“…This is broadly consistent with evidence that even severe forebrain injury does not affect FHRV, supporting the hypothesis that the hindbrain is essentially the sole origin of HRV in the fetus 58 . Of particular interest, one study in preterm fetal sheep has shown that the brainstem was relatively spared from LPS-induced injury and inflammatory changes despite LPS triggering cerebellar injury 56 .…”

Physiological control of fetal heart rate variability during labour: implications and controversies

“…In the fetus at least, normal FHRV seems to be almost entirely mediated by the brainstem, with full recovery of FHRV after severe forebrain ischaemic injury in near‐term fetal sheep (Maeda et al . 2021).…”

“…At a systemic level, the appearance of a normal FHR and FHRV amplitude and pattern including regular sleep cycling, as shown by alternate periods of high and low absolute levels, is widely believed to represent an expression of a healthy, fully intact central nervous system (Ugwumadu, 2014). In the fetus at least, normal FHRV seems to be almost entirely mediated by the brainstem, with full recovery of FHRV after severe forebrain ischaemic injury in near-term fetal sheep (Maeda et al 2021).…”