Multi-lag tone–entropy in neonatal stress

Heart rate variability (HRV) has been analysed using linear and nonlinear methods. In the framework of a controlled neonatal stress model, we applied tone-entropy (T-E) analysis at multiple lags to understand the influence of external stressors on healthy term neonates. Forty term neonates were included in the study. HRV was analysed using multi-lag T-E at two resting and two stress phases (heel stimulation and a heel stick blood drawing phase). Higher mean entropy values and lower mean tone values when stressed showed a reduction in randomness with increased sympathetic and reduced parasympathetic activity. A ROC analysis was used to estimate the diagnostic performances of tone and entropy and combining both features. Comparing the resting and simulation phase separately, the performance of tone outperformed entropy, but combining the two in a quadratic linear regression model, neonates in resting as compared to stress phases could be distinguished with high accuracy. This raises the possibility that when applied across short time segments, multi-lag T-E becomes an additional tool for more objective assessment of neonatal stress.