A pilot cohort study of cerebral autoregulation and 2-year neurodevelopmental outcomes in neonates with hypoxic-ischemic encephalopathy who received therapeutic hypothermia

Abstract

BackgroundNeurodevelopmental disabilities persist in survivors of neonatal hypoxic-ischemic encephalopathy (HIE) despite treatment with therapeutic hypothermia. Cerebrovascular autoregulation, the mechanism that maintains cerebral perfusion during changes in blood pressure, may influence outcomes. Our objective was to describe the relationship between acute autoregulatory vasoreactivity during treatment and neurodevelopmental outcomes at 2 years of age.MethodsIn a pilot study of 28 neonates with HIE, we measured cerebral autoregulatory vasoreactivity with the hemoglobin volume index (HVx) during therapeutic hypothermia, rewarming, and the first 6 h of normothermia. The HVx, which is derived from near-infrared spectroscopy, was used to identify the individual optimal mean arterial blood pressure (MAPOPT) at which autoregulatory vasoreactivity is greatest. Cognitive and motor neurodevelopmental evaluations were completed in 19 children at 21–32 months of age. MAPOPT, blood pressure in relation to MAPOPT, blood pressure below gestational age + 5 (ga + 5), and regional cerebral oximetry (rSO2) were compared to the neurodevelopmental outcomes.ResultsNineteen children who had HIE and were treated with therapeutic hypothermia performed in the average range on cognitive and motor evaluations at 21–32 months of age, although the mean performance was lower than that of published normative samples. Children with impairments at the 2-year evaluation had higher MAPOPT values, spent more time with blood pressure below MAPOPT, and had greater blood pressure deviation below MAPOPT during rewarming in the neonatal period than those without impairments. Greater blood pressure deviation above MAPOPT during rewarming was associated with less disability and higher cognitive scores. No association was observed between rSO2 or blood pressure below ga + 5 and neurodevelopmental outcomes.ConclusionIn this pilot cohort, motor and cognitive impairments at 21–32 months of age were associated with greater blood pressure deviation below MAPOPT during rewarming following therapeutic hypothermia, but not with rSO2 or blood pressure below ga + 5. This suggests that identifying individual neonates’ MAPOPT is superior to using hemodynamic goals based on gestational age or rSO2 in the acute management of neonatal HIE.Electronic supplementary materialThe online version of this article (doi:10.1186/s12883-015-0464-4) contains supplementary material, which is available to authorized users.

Cerebral Autoregulation and Conventional and Diffusion Tensor Imaging Magnetic Resonance Imaging in Neonatal Hypoxic-Ischemic Encephalopathy

“…In the current study, we extend our prior work 5,6,11,12 to validate the relationships between blood pressure, optimal MAP, and brain injury using qualitative and quantitative MRIs with the NRN brain injury score 2 and DTI MD scalars in neonates younger than 10 days. We hypothesized that both the NRN score and MD scalars would detect relationships between blood pressure deviation from optimal MAP and brain injury in newborns with HIE.…”

“…Inclusion criteria, which included a diagnosis of moderate to severe HIE based on the National Institute of Child Health and Human Development clinical trial of hypothermia 14 and gestational age ≥35 weeks, have been reported previously. 5,6,11 Only neonates who underwent a brain MRI on a 1.5 Tesla (T) scanner before the tenth day of life were eligible for the study. Exclusion criteria included congenital anomalies that could make cooling unsafe, coagulopathy with active bleeding, and absence of an arterial blood pressure catheter.…”

“…We reported autoregulation and MRI data from a subset of these neonates in our prior studies. 5,6,11,12 …”

“…Cerebral vasoreactivity describes the vasodilatory and vasoconstrictive responses to changes in blood pressure that mediate cerebral blood flow autoregulation. Dysfunctional vasoreactivity and autoregulation during resuscitation, 3 hypothermia, 4 and rewarming 5,6 may contribute to secondary brain injury and poor neurological outcomes in HIE.…”

“…Using optimal MAP as a hemodynamic goal to optimize autoregulatory vasoreactivity in individual neonates reflects a precision medicine approach that contrasts with using generalized blood pressure goals, such as those based on gestational age, that assume similar hemodynamic needs among all neonates. We previously demonstrated a relationship between blood pressure relative to optimal MAP and brain injury on magnetic resonance imaging (MRI) 5,11,12 and neurodevelopmental outcomes 6 in a small cohort of babies with HIE.…”