Perinatal Events and Early Magnetic Resonance Imaging in Therapeutic Hypothermia

Abstract

The incidence of hypoxic-ischemic encephalopathy (HIE) is 1 to 2 in 1000 live births. A number of randomized controlled trials have demonstrated that therapeutic hypothermia reduces death or severe disability in neonates with HIE, and this therapy is used in many centers. The pattern of brain injury and its severity assessed by magnetic resonance imaging (MRI) is commonly used as a predictor of outcome among infants with HIE. Therapeutic hypothermia has been associated with a reduction of lesions in the basal ganglia or thalamus in comparison with noncooled infants, and treated neonates are more likely to have normal scans. MRI findings have been predictive of later neuromotor abnormalities. The relationship between perinatal events and MRI findings in neonates treated with therapeutic hypothermia has not been assessed. The overall aim of this ongoing cohort study was to compare the relationship between the pattern and severity of HIE brain injury and perinatal events assessed by early MRI among infants with and without therapeutic hypothermia. Perinatal events evaluated included decreased fetal movements and sentinel (acute asphyxial) events. MRI was performed in neonates with HIE; 35 received therapeutic hypothermia and 25 were untreated. An MRI scoring system was used to categorize predominant injury patterns as watershed (WS) or basal ganglia/thalamus(BG/T) or normal as well as a dichotomous outcome of normal-mild injury versus moderate-severe brain injury. Compared with untreated neonates, treated neonates had significantly less extensive brain injury to WS and BG/T regions and a significantly higher proportion of normal imaging (P = 0.02 for all comparisons). Among treated infants, there was a significantly reduced frequency of both BG/T-predominant injury (relative risk, 0.29; 95% confidence interval [CI], 0.10–0.81; P = 0.01) and the dichotomous outcome of moderate-severe brain injury (odds ratio, 0.16; 95% confidence interval, 0.05–0.52; P = 0.002). Following treatment of neonates with sentinel events, there was a decrease in BG/T-predominant injury and an increase in normal imaging. All neonates with decreased fetal movements had some degree of injury, despite hypothermia; the most common (>80%) was WS-predominant injury. In addition to confirming previous reports that therapeutic hypothermia reduces brain injury among neonates with HIE, these findings suggest that perinatal factors may serve as important indicators of response to treatment.