Key result
In preterm fetal sheep, hypoxia-ischaemia was associated with early suppression of fetal heart rate variability and loss of circadian rhythms, followed by exaggerated rhythms over the final 2 weeks.
Why the study?
Antenatal hypoxia-ischaemia is a key risk factor for stillbirth and severe neurodevelopmental disability, but reliable biomarkers to detect at-risk fetuses are lacking.
Does hypoxia-ischaemia alter circadian patterns of fetal heart rate variability in preterm fetal sheep?
Does hypoxia-ischaemia alter circadian patterns of fetal heart rate variability in preterm fetal sheep?
Circadian changes in fetal heart rate variability may serve as a low-cost, easily applied biomarker of antenatal hypoxia-ischaemia and evolving brain injury.
Answers are grounded in this paper and cite their sources.
May enable post-HI FHRV biomarkers in preterm fetuses; hypothesis-generating in sheep and requires human validation.
Hypoxia-ischaemia (HI) before birth is a key risk factor for stillbirth and severe neurodevelopmental disability in survivors, including cerebral palsy, although there are no reliable biomarkers to detect at risk fetuses that may have suffered a transient period of severe HI. We investigated time and frequency domain measures of fetal heart rate variability (FHRV) for 3 weeks after HI in preterm fetal sheep at 0.7 gestation (equivalent to preterm humans) until 0.8 gestation (equivalent to term humans). We have previously shown that this is associated with delayed development of severe white and grey matter injury, including cystic white matter injury (WMI) resembling that observed in human preterm infants. HI was associated with suppression of time and frequency domain measures of FHRV and reduced their circadian rhythmicity during the first 3 days of recovery. By contrast, circadian rhythms of multiple measures of FHRV were exaggerated over the final 2 weeks of recovery, mediated by a greater reduction in FHRV during the morning nadir, but no change in the evening peak. These data suggest that the time of day at which FHRV measurements are taken affects their diagnostic utility. We further propose that circadian changes in FHRV may be a low-cost, easily applied biomarker of antenatal HI and evolving brain injury. KEY POINTS: Hypoxia-ischaemia (HI) before birth is a key risk factor for stillbirth and probably for disability in survivors, although there are no reliable biomarkers for antenatal brain injury. In preterm fetal sheep, acute HI that is known to lead to delayed development of severe white and grey matter injury over 3 weeks, was associated with early suppression of multiple time and frequency domain measures of fetal heart rate variability (FHRV) and loss of their circadian rhythms during the first 3 days after HI. Over the final 2 weeks of recovery after HI, exaggerated circadian rhythms of frequency domain FHRV measures were observed. The morning nadirs were lower with no change in the evening peak of FHRV. Circadian changes in FHRV may be a low-cost, easily applied biomarker of antenatal HI and evolving brain injury.
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Lear et al. (2023) studied Hypoxia-ischaemia. Hypoxia-ischaemia was evaluated on Time and frequency domain measures of fetal heart rate variability (FHRV) and their circadian rhythmicity. In preterm fetal sheep, hypoxia-ischaemia was associated with early suppression of fetal heart rate variability and loss of circadian rhythms, followed by exaggerated rhythms over the final 2 weeks.
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