Abstract
Hypotension or low blood pressure (BP) is a common problem in preterm neonates and has been associated with adverse short and long-term neurological outcomes. Deciding when and whether to treat hypotension relies on an understanding of the relationship between BP and brain functioning. This study aims to investigate the interaction (coupling) between BP and continuous multichannel unedited EEG recordings in preterm infants less than 32 weeks of gestational age. The EEG was represented by spectral power in four frequency sub-bands: 0.3–3 Hz, 3–8 Hz, 8–15 Hz and 15–30 Hz. BP was represented as mean arterial pressure (MAP). The level of coupling between the two physiological systems was estimated using linear and nonlinear methods such as correlation, coherence and mutual information. Causality of interaction was measured using transfer entropy. The illness severity was represented by the clinical risk index for babies (CRIB II score) and contrasted to the computed level of interaction. It is shown here that correlation and coherence, which are linear measures of the coupling between EEG and MAP, do not correlate with CRIB values, whereas adjusted mutual information, a nonlinear measure, is associated with CRIB scores (r = -0.57, p = 0.003). Mutual information is independent of the absolute values of MAP and EEG powers and quantifies the level of coupling between the short-term dynamics in both signals. The analysis indicated that the dominant causality is from changes in EEG producing changes in MAP. Transfer entropy (EEG to MAP) is associated with the CRIB score (0.3–3 Hz: r = 0.428, p = 0.033, 3–8 Hz: r = 0.44, p = 0.028, 8–15 Hz: r = 0.416, p = 0.038) and indicates that a higher level of directed coupling from brain activity to blood pressure is associated with increased illness in preterm infants. This is the first study to present the nonlinear measure of interaction between brain activity and blood pressure and to demonstrate its relation to the initial illness severity in the preterm infant. The obtained results allow us to hypothesise that the normal wellbeing of a preterm neonate can be characterised by a nonlinear coupling between brain activity and MAP, whereas the presence of weak coupling with distinctive directionality of information flow is associated with an increased mortality rate in preterms.
Highlights
Prematurity is the leading cause of death in children under the age of five [1] with more than 1 million children dying each year due to the complications of preterm birth
A low mean arterial pressure (MAP) correlates with high correlations sharing one variable (CRIB) scores, Fig 12C, where higher risks of mortality are associated with lower MAP values (r = -0.503, p = 0.01). This association could be indirectly associated to gestational age, as CRIB scores and MAP are both dependent on the GA
Our findings suggest that nonlinear measures of interaction are more suitable when measuring coupling between the complex system of brain function and blood pressure (BP)
Summary
Prematurity is the leading cause of death in children under the age of five [1] with more than 1 million children dying each year due to the complications of preterm birth. Hypotension, or low blood pressure (BP), is a common problem in preterm babies, in the first 72 hours after delivery It may cause decreased cerebral perfusion, resulting in impaired oxygen delivery to the brain [5]. Treatment often involves administration of volume expanders and inotropes with dopamine as a first-line agent when the mean arterial pressure (MAP) (in mm Hg) falls below the gestational age (GA) in weeks [8]. This approach is not supported by any robust scientific evidence [9]. Preterm infants whose brain function is potentially impacted by low BP, may require treatment
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