Exploratory Assessment of the Relationship Between Hemoglobin Volume Phase Index, Magnetic Resonance Imaging, and Functional Outcome in Neonates with Hypoxic–Ischemic Encephalopathy

Background/Objective: Near-infrared spectroscopy (NIRS)-based measures of cerebral autoregulation (CAR) can potentially identify neonates with hypoxic–ischemic encephalopathy (HIE) who are at greatest risk of irreversible brain injury. However, modest predictive abilities have precluded previously described metrics from entering clinical care. We previously validated a novel autoregulation metric in a piglet model of induced hypotension called the hemoglobin volume phase index (HVP). The objective of this study was to evaluate the clinical ability of the HVP to predict adverse outcomes neonates with HIE. Methods: This is a prospective study of neonates with HIE who underwent therapeutic hypothermia (TH) at a level 4 neonatal intensive care unit (NICU). Continuous cerebral NIRS and mean arterial blood pressure (MAP) from indwelling arterial catheters were measured during TH and through rewarming. Multivariate autoregressive process was used to calculate the coherence between MAP and the sum total of the oxy- and deoxygenated Hb densities (HbT), a surrogate measure of cerebral blood volume (CBV). The HVP was calculated as the cosine-transformed phase shift at the frequency of maximal MAP-HbT coherence. Brain injury was assessed by neonatal magnetic resonance imaging (MRI), and developmental outcomes were assessed by the Bayley Scales of Infant Development (BSID-III) at 15–30 months. The ability of the HVP to predict (a) death or severe brain injury by MRI and (b) death or significant developmental delay was assessed using logistic regression analyses. Results: In total, 50 neonates with moderate or severe HIE were monitored. Median HVP was higher, representing more dysfunctional autoregulation, in infants who had adverse outcomes. After adjusting for sex and encephalopathy grade at presentation, HVP at 21–24 and 24–27 h of life predicted death or brain injury by MRI (21–24 h: OR 8.8, p = 0.037; 24–27 h: OR 31, p = 0.011) and death or developmental delay at 15–30 months (21–24 h: OR 11.8, p = 0.05; 24–27 h: OR 15, p = 0.035). Conclusions: Based on this pilot study of neonates with HIE, HVP merits further study as an indicator of death or severe brain injury on neonatal MRI and neurodevelopmental delay in early childhood. Larger studies are warranted for further clinical validation of the HVP to evaluate cerebral autoregulation following HIE.