Therapeutic Hypothermia for Treatment of Neonatal Encephalopathy

Current Research and Nursing Care

Carmen K. Cederholm, BSN, RN, CCRN; C. Michael Cotten, MD, MHS


NAINR. 2014;14(2):77-81. 

In This Article

New Topics in Therapeutic Hypothermia Research

Early research has shown that TH can be beneficial in the treatment of NE. However, researchers are now attempting to identify methods for real-time assessment of effectiveness of treatment and ways to predict outcomes. Knowledge pertaining to these topics could aid in counseling parents as well as finding complimentary treatments.


Magnetic resonance imaging (MRI) is a useful tool for defining the extent of brain injury in infants following perinatal asphyxia. A main focus in current literature is research aimed at expanding the utility of MRI beyond diagnosis. Studies are now reporting evaluations of MRI in measuring the effectiveness of TH as well as predicting neurodevelopmental outcomes. Additional information is being sought to determine appropriate timing of scans and whether TH interferes with the reliability of MRI readings.

Shankaran, et al. (2011) compared MRIs performed at 44 weeks gestational age and categorized by pattern of injury to neurodevelopmental assessments at 18–22 months.[21] Because some patterns of injury did not fit into earlier defined systems of categorization, a method called the NICHD Neonatal Research Network (NRN) pattern of injury was created that classified injuries into six groups. The most common pattern of injury included damage to the posterior limb of the internal capsule (PLIC), the anterior limb of the internal capsule (ALIC), or the basal ganglia and thalami (BGT). Infants in the hypothermia group tended to have more normal appearing MRIs, normal PLIC and ALIC, and significantly fewer areas of watershed infarction. They found excellent correlation between the NICHD NRN pattern of injury categorization system and the primary outcome of death or disability at 18–22 months. Additionally, there was no statistically significant effect of age at time of scan on the prognostic utility of the NICHD NRN pattern of injury system.[21]

Rutherford, et al. (2010) and Cheong, et al. (2012) analyzed T1 and T2 weighted MRIs and performed sub-studies of infants in the TOBY and ICE trials, respectively.[22,23] Lesions were categorized into 1 of 5 patterns of injury as defined by Okeraefor, et al.[24] Cheong, et al. found moderate to severe injuries in certain regions to be prognostic of poor outcomes at 2 years of age.[23] In both studies, cooled infants were more likely to have a normal scan and had reduced incidence and severity of MRI abnormalities in the basal ganglia and thalami as well as the white and gray matter.[22,23] They also inferred that MRIs performed during the neonatal period were predictive of outcomes at 18 months and 2 years and were not affected by TH.[22,23] Both groups suggest that timing of MRI may affect the reliability of the reading. Rutherford, et al. discovered more major abnormalities on infants scanned at less than 8 days of age when compared to those scanned at greater than 8 days of age.[22] The variation may be due to spontaneous resolution of lesions or increased severity of disease for those scanned earlier. Because the reason for differences in timing of obtaining MRI was unknown, generalizations about optimal timing were unable to be ascertained.[22]

Tusor, et al. (2012) aimed to identify an early biomarker that could help assess the efficacy of a treatment.[25] They also hypothesized that MRI results could be used to predict neurodevelopmental outcomes in infants with NE. The MRIs were evaluated using tract-based spatial statistical (TBSS) analysis of diffusion tensor imaging (DTI). DTI can be used to make presumptions about the underlying microstructure of tissue using the random motion of water molecules within that tissue. TBSS is an observer-independent, multi-subject analysis tool that can be used to assess DTI data for white matter degenerative changes. This study compared measures derived from DTI with results of Griffiths Mental Development Scales (Revised) (GMDS-R) performed at 24–28 months of age. They found TBSS to be more accurate at predicting outcomes than HIE staging. Their findings also suggest that TBSS can be used as an early biomarker to study additional neuroprotective interventions.[25]

HIE Staging

Shankaran, et al. (2012) hypothesized that the clinical course of NE, as measured by serial neurological exams, could have prognostic utility.[26] Modified Sarnat exams were performed at greater than 6, 24, 48, and 72 hours during the intervention and once again at discharge. Follow-up with 204 surviving infants was performed at 18–22 months when they were assessed for severe disability. There was no significant difference in stage of encephalopathy at greater than 6 and at 72 hours as well as at discharge. However, the cooled group had earlier improvement in stage of encephalopathy, with reduced staging at 24 and 48 hours. Persistent severe encephalopathy through the 72-hour mark was strongly correlated with increased risk of death or severe disability at 18 months of age. They suggest that NE stage at the end of cooling intervention can be used as a good predictor of the risk of death or severe disability.[26]