Neurodevelopmental 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. In 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. Nineteen 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. In 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.

Prior to therapeutic hypothermia (that is, cooling), transfontanellar duplex brain sonography resistive indices (RI) were studied as a bedside non-invasive measures of cerebral hemodynamics in neonates who suffered from hypoxic-ischemic encephalopathy (HIE). We compared pre- and post-cooling RI values and examined the relationships between RI values and specific long-term neurodevelopmental outcomes. Transfontanellar duplex brain sonography, including RI, were obtained for 28 neonates prior to cooling and for 20 neonates following cooling. All RI values were sampled in the anterior cerebral artery at the beginning of each ultrasound study. Neurodevelopmental assessment was conducted between ages 20–32 months with the Mullen Scale of Early Learning. The relationships between pre- and post-cooling RI and cognitive and motor outcomes were studied. Neonates with RI values 0.60. Lower RI values were associated with specific neurodevelopmental deficits in motor skill attainment. Pre- and post-cooling transfontanellar duplex brain sonography RI values may be a useful prognostic tool, in conjunction with other clinical information, for neonates diagnosed with HIE. The results of this study suggest that further study of the prognostic value of RI values for short- and long-term outcomes is warranted.

Early studies following perinatal hypoxic-ischemic encephalopathy (HIE) suggested expressive language deficits and academic difficulties, but there is only limited detailed study of language development in this population since the widespread adoption of therapeutic hypothermia (TH). Expressive and receptive language testing was performed as part of a larger battery with 45 children with a mean age of 26 months following perinatal HIE treated with TH. Overall cohort outcomes as well as the effects of gender, estimated household income, initial pH and base excess, and pattern of injury on neonatal brain MRI were assessed. The cohort overall demonstrated expressive language subscore, visual-reception subscore, and early learning composite scores significantly below test norms, with relative sparing of receptive language subscores. Poorer expressive language manifested as decreased vocabulary size and shorter utterances. Expressive language subscores showed a significant gender effect, and estimated socioeconomic status showed a significant effect on both receptive and expressive language subscores. Initial blood gas markers and modified Sarnat scoring did not show a significant effect on language subscores. Binarized MRI abnormality predicted a significant effect on both receptive and expressive language subscores; the presence of specific cortical/subcortical abnormalities predicted receptive language deficits. Overall, the language development profile of children following HIE in the era of hypothermia shows a relative strength in receptive language. Gender and socioeconomic status predominantly predict expressive language deficits; abnormalities detectable on MRI predominantly predict receptive language deficits.