Neonatal encephalopathy and associated brain injury is a serious problem that results in an estimated 1 million annual neonatal deaths despite major advances in obstetrics and neonatal care. Recent studies have shown that cooling babies who suffer neonatal brain injury to 33.5? C for 72 hours, a process known as Therapeutic Hypothermia (TH), can markedly reduce brain injury in about 50% of affected babies. However, it appears to be more effective in neonates who have a sentinel event at the time of birth and basal ganglia injury on MRI than in those with intervascular boundary zone ("watershed") injury identified on MRI. Neither the exact mechanisms by which TH reduces brain injury nor the reasons that the treatment is effective in some babies but not others are understood. It is known that neonatal brain injuries have a mixture of characteristics and, probably different mechanisms. Therefore, different treatments might eventually be tailored to individual babies based upon the type of injury and response to initial therapy. This study proposes to use techniques involving magnetic resonance imaging, called diffusion tensor imaging (DTI) and proton MR spectroscopy (MRS) in the neonatal period to assess which types of injury respond best to TH. A later MRI study at age 6 months from this cohort will use more sophisticated methods to evaluate how severe the injury was and how well the body was able to repair the injury with the help of TH as compared to prior studies without TH. Finally, MRI scans will be obtained at ages of 8-10 years from patients that were enrolled in an earlier study. Children who had very similar injuries will be grouped together and the MRI results will be used to see what MRI characteristics (using the more sophisticated MRI methods) are found in the children who recovered best from their injury but not in those who did not recover well. These MRI characteristics will be designated as "markers of brain repair" after neonatal injury. Knowledge of these markers will help to more quickly evaluate new therapeutic interventions being used to increase repair after neonatal brain injury.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Program Projects (P01)
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National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
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University of California San Francisco
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Jenster, Meike; Bonifacio, Sonia L; Ruel, Theodore et al. (2014) Maternal or neonatal infection: association with neonatal encephalopathy outcomes. Pediatr Res 76:93-9