Cerebral Hemodynamics in Asphyxiated Newborns Undergoing Hypothermia Therapy: Pilot Findings Using a Multiple-Time-Scale Analysis

Abstract

Background: Improved quantitative assessment of cerebral hemodynamics in newborns might enable us to optimize cerebral perfusion. Our objective was to develop an approach to assess cerebral hemodynamics across multiple time scales during the first 72 hours of life in newborns during hypothermia therapy.

Methods: Spontaneous oscillations in mean arterial pressure and regional cerebral tissue oxygen saturation were analyzed using a moving window correlation method with time scales ranging from 0.15 to 8 hours in this pilot methodology study. Abnormal neurodevelopmental outcome was defined by Bayley III scores and/or cerebral palsy by age 24 months using receiver operating curve.

Results: Multiple-time-scale correlations between the mean arterial pressure and regional cerebral tissue oxygen saturation oscillations were tested in 10 asphyxiated newborns undergoing hypothermia therapy. Large noninduced fluctuations in the blood pressure were observed during cooling in all five infants with abnormal outcomes. Notably, these infants had two distinct patterns of correlation: a positive in-phase correlation at the short time scales (15 minutes) and/or a negative antiphase correlations observed at long time scales (4 hours.). Both the in-phase (area under the curve 0.6, [95% confidence interval 0.2-0.95]) and antiphase correlations (area under the curve 0.75, [95% confidence interval 0.4-0.95]) appeared to be related to an abnormal outcome.

Conclusions: Our observations suggest that the time scale is an important factor that needs to be standardized in the assessment of neonatal cerebral hemodynamics.

Keywords: cerebral hemodynamics; hypothermia; hypoxic-ischemic encephalopathy (HIE); near infrared spectroscopy (NIRS); neonate.

Figure 1

a. Data processing and analysis procedures. Mean arterial pressure (MAP) and cerebral tissue oxygen saturation (S_ctO₂) were recorded every 30 seconds. The raw data were inspected through a spike-detection algorithm to identify any measurement artifacts. 1b. Spike-like data points were replaced with linearly interpolated values from their nearest neighbors. 1c. Pearson’s correlation coefficient (R) between MAP and S_ctO₂ was computed within a moving window. The window size increased over time scales of 1/8, 1/4, 1/2, 1, 2, 4, and 8 hours.

Figure 2

Examples of the different patterns of hemodynamics noted during cooling in infants with abnormal outcomes. Mean arterial pressure (MAP) and cerebral tissue oxygen saturation (S_ctO₂) are depicted on the y axis, time on the x axis in: (2a.) newborn with positive correlation, and (2b.) newborn with negative correlation both of whom had abnormal outcomes.

Figure 3

Cerebral hemodynamics index (CH index) derived from the multiple-time-scale correlation analysis. The CH index values in the selected 10 newborns are plotted against the five time scales of 7min, 15min, 30 min, 1hr, 2hr, 4hr and 8 hr. At each time scale, the CH index was calculated for significant correlation coefficient R>0.5 (left) and R< −0.5 (right).