Introduction: Therapeutic hypothermia improves outcomes after acute hypoxic-ischaemic (HI) injury, but many infants do not benefit. A key factor is that in many cases timely recruitment is challenging. We evaluated the utility of heart rate patterns and arginine vasopressin (AVP) levels after HI as potential biomarkers of the severity of HI in the early latent phase.
Materials and Methods: Chronically instrumented fetal sheep at 0.85 gestational age received different durations of umbilical cord occlusion (UCO) to produce mild (n=6), moderate (n=8) or severe HI (n=8) or sham occlusion (n=5). Fetal heart rate (FHR) patterns were visually assessed during the first 2 hours after UCO. Sinusoidal FHR patterns persisting for three minutes or more were identified. Fetal arterial blood samples were taken before and after UCO to measure serum AVP levels.
Results: Intermittent periods of sinusoidal heart rate patterns in the first hour after HI were identifed in 1/8 fetuses with moderate and 6/8 cases of severe HI, but not after mild HI. Serum AVP values were significantly increased at 1 hour after UCO in the moderate and severe groups compared to sham controls (P<0.005), and were greater after severe HI than moderate HI (259 ± 100 pmol/l vs 87 ± 68 pmol/l, median ± IQR, P<0.01). Intriguingly, AVP concentrations were positively correlated with the duration of sinusoidal patterns in the first hour after UCO (r2=0.57, P<0.005).
Conclusion: Both sinusoidal FHR patterns and increased AVP levels in the first hour after UCO were associated with more severe HI suggesting potential for clinical utility. The significant correlation between FHR changes and serum AVP is consistent with previous evidence that in healthy fetal sheep parasympathetic-blockade plus AVP infusions can induce a sinusoidal pattern (Murata et al., 1985), suggesting that the association may be causal.