Fetal brain response to worsening acidosis: an experimental study in a fetal sheep model of umbilical cord occlusions

Abstract

Perinatal anoxia remains an important public health problem as it can lead to hypoxic-ischaemic encephalopathy (HIE) and cause significant neonatal mortality and morbidity. The mechanisms of the fetal brain's response to hypoxia are still unclear and current methods of in utero HIE prediction are not reliable. In this study, we directly analysed the brain response to hypoxia in fetal sheep using in utero EEG. Near-term fetal sheep were subjected to progressive hypoxia induced by repeated umbilical cord occlusions (UCO) at increasing frequency. EEG changes during and between UCO were analysed visually and quantitatively, and related with gasometric and haemodynamic data. EEG signal was suppressed during occlusions and progressively slowed between occlusions with the increasing severity of the occlusions. Per-occlusion EEG suppression correlated with per-occlusion bradycardia and increased blood pressure, whereas EEG slowing and amplitude decreases correlated with arterial hypotension and respiratory acidosis. The suppression of the EEG signal during cord occlusion, in parallel with cardiovascular adaptation could correspond to a rapid cerebral adaptation mechanism that may have a neuroprotective role. The progressive alteration of the signal with the severity of the occlusions would rather reflect the cerebral hypoperfusion due to the failure of the cardiovascular adaptation mechanisms.

Figure 1

Experimental protocol. At day 4 after surgery: progressive anoxia induced by repeated umbilical cord occlusions of increasing frequency.

Figure 2

Example of fetal sheep EEG tracing during cord occlusion. A diminution of the signal amplitude can be seen during this UCO in phase B (1 min of occlusion every 3 min)—90 s epoch. The red bar mark the occlusion. Transverse bipolar montage with derivations 1–2 corresponding to left and right frontal electrodes and 3–4 to left and right parietal electrodes.

Figure 3

Two examples of fetal sheep EEG tracings before and during cord occlusions. Extracts pre-occlusion in stability phase (S) and between occlusions in mild phase (A), moderate phase (B) and severe phase (C)—30 s epochs. EEG signal alteration can be seen in both fetuses from moderate occlusions phase with slowing and decrease in amplitude. Transverse bipolar montage with derivations 1–2 corresponding to left and right frontal electrodes and 3–4 to left and right parietal electrodes.

Figure 4

Example of qEEG curves in a fetus in stability phase and during the protocol of progressive hypoxia. (1) Evolution of BSR (%), SEF (Hz) and minAI (µV) values in stability phase (S), in mild occlusions phase (A), moderate occlusions phase (B) and severe occlusions phase (C), of 1 h each in fetal sheep 3. O = total cord occlusion (1 min). (2) 30-s EEG extracts in stability phase and at the end of a mild and severe occlusion.

Figure 5

Example of BSR curve during the three occlusions phases of increasing severity. Phase A: mild occlusions (1ʹ/5ʹ). Phase B: moderate occlusions (1ʹ/3ʹ). Phase C: severe occlusions (1ʹ/2ʹ). O = onset of cord occlusion (1 min). pH on the x-axis.