Evolving changes in fetal heart rate variability and brain injury after hypoxia-ischaemia in preterm fetal sheep.

Hypoxia-ischaemia (HI) is a major contributor to preterm brain injury, although there are currently no reliable biomarkers for identifying infants who are at risk. We tested the hypothesis that fetal heart rate (FHR) and FHR variability (FHRV) would identify evolving brain injury after HI. Fetal sheep at 0.7 of gestation were subjected to either 15 (n = 10) or 25 min (n = 17) of complete umbilical cord occlusion or sham occlusion (n = 12). FHR and four measures of FHRV [short-term variation, long-term variation, standard deviation of normal to normal R-R intervals (SDNN), root mean square of successive differences) were assessed until 72 h after HI. All measures of FHRV were suppressed for the first 3-4 h in the 15 min group and 1-2 h in the 25 min group. Measures of FHRV recovered to control levels by 4 h in the 15 min group, whereas the 25 min group showed tachycardia and an increase in short-term variation and SDNN from 4 to 6 h after occlusion. The measures of FHRV then progressively declined in the 25 min group and became profoundly suppressed from 18 to 48 h. A partial recovery of FHRV measures towards control levels was observed in the 25 min group from 49 to 72 h. These findings illustrate the complex regulation of FHRV after both mild and severe HI and suggest that the longitudinal analysis of FHR and FHRV after HI may be able to help determine the timing and severity of preterm HI.