The HYPOTOP Trial is a multi-center double-blinded randomized clinical trial which is led by our group. This study is based on the investigation of the effects of hypothermia on moderate to severe hypoxic ischemic encephalopathy (HIE) in term newborns, which is causing infantile cerebral palsy and mental retardation. In this clinical trial two groups are compared, both subjected to moderate prolonged hypothermia, one receiving topiramate and the other one a placebo. The main objective of the study is to investigate the clinical outcomes of patients treated with hypothermia and topiramate. Furthermore, pharmacodynamics of topiramate and monitoring the concentrations of topiramate in plasma at several time points during treatment are studied. In addition, oxidative stress and damage on the central nervous system are evaluated using biomarkers determined employing LC-MS/MS methods that allow the quantification of the studied biomarkers in a complex samples matrix at very low concentrations. Having access to this pool of clinical and biochemical information opens the doors for an innovative approach based on untarget metabolomics for the dynamic monitoring of the effect of hypothermia with topiramate vs. hypothermia with placebo, which will also be evaluated in the course of this trial.