Kim Annink

17 General introduction (43). Therefore, in chapter five we investigate the association between HIE, hippocampal volume at ten years of age and cognitive outcome in the above described cohort. We do not have this ten year outcome information of children with HIE treated with hypothermia. Follow-up until six to seven years of age of the TOBY trial, one of the large RCTs investigating the effect therapeutic hypothermia in HIE, showed that significantly more children in the hypothermia group (52%) compared to the control group (39%) survived with an IQ above 85 points (1). Nevertheless, health related quality of life was comparable between the groups (44). Childhood outcome of another trial revealed that 27% of the surviving children treated with hypothermia had an IQ below 70 and 33% in the control group (45). The frequency of CP declined from 29% in controls to 17% in children treated with hypothermia in this study (45). Although neurodevelopmental outcome in childhood has improved with therapeutic hypothermia, as stated above, there is still a significant number of children with HIE that experience long-term neurodevelopmental problems. Information about which regions of the brain are still vulnerable for hypoxic-ischemic injury despite therapeutic hypothermia would be helpful, for clinicians to better predict outcome and for researchers to develop new neuroprotective strategies. However, childhood MRI studies exploring the association between brain injury and childhood outcomes are lacking. Therefore, we conducted a prospective observational cohort study assessing cognition, memory, motor functioning and MRI at ten years of age in children with HIE following perinatal asphyxia that were treated with therapeutic hypothermia and those who were born before therapeutic hypothermia became standard of care . The results of this study are presented in chapter six. Add-on neuroprotective therapies Since HIE still is a burden to patients and their family despite the current treatment with hypothermia, additional neuroprotective add-on therapies are essential to further reduce brain injury in neonates with HIE and to optimize their future perspectives. HIE also comes with a financial burden to society. Based on the six to seven year outcome data of the TOBY trial, the healthcare costs for infants in the United Kingdom who were cooled and those who were not were compared. Healthcare costs were £2549 per child per six months for controls and £1543 per child per six 1