Cerebral Injury in Perinatal Asphyxia, epidemiological, clinical, neurophysiological and neuromatabolic investigations

University dissertation from Kristina Thorngren-Jerneck, Department of Paediatrics, University Hospital, SE-221 85 Lund

Abstract: Perinatal asphyxia with hypoxic ischemic encephalopathy (HIE) is the most important cause of perinatal mortality and cerebral palsy (CP) in infants born at term. The aim of the thesis was to investigate epidemiology of perinatal asphyxia, and to investigate early clinical neurological symptoms after perinatal asphyxia in relation to cerebral glucose metabolism (CMRgl) measured by 18-FDG-PET, neurophysiological function, some biochemical markers, also in relation to long-term outcome. The main purpose was to investigate hypoxic-ischemic brain injury in relation to cerebral metabolism, neurophysiology, and neurochemistry in order to evaluate prognostic tools after perinatal asphyxia. After the hypoxic-ischemic event there is evidence of a time-window before the permanent brain injury is established. In the near future, interventional treatment for hypoxic-ischemic brain injury may become a reality in infants born at term who have suffered perinatal asphyxia and hypoxia-ischemia. It is therefore of high priority to evaluate methods for early prediction of outcome that could be used for selecting infants with the highest risks of developing brain injury after asphyxia. The epidemiological problem of perinatal asphyxia was defined in two large population-based studies. The first study showed several obstetric and infant risk factors (e.g. breech presentation, high birth weight) to be associated with low 5 minute Apgar score in term infants. Mortality and the risk for severe neurological morbidity (CP, epilepsy and mental retardation) were increased in these infants. The second study showed that the majority (65 %) of children with CP are born at term. In term infants there is a strong correlation between some perinatal risk factors (abruptio placentae, breech presentation and low Apgar score) and development of CP. Cerebral glucose metabolism, measured by FDG-PET in the sub-acute period after perinatal asphyxia, was significantly reduced in term infants who developed moderate or severe HIE and subsequently CP. Early postnatal electro-cortical background activity, and delayed epileptic seizure activity were significantly correlated with CMRgl measured during the sub-acute phase after asphyxia, reflecting the degree of cerebral injury. The fifth study showed postnatal increased serum S100 reflecting the extent of brain damage in infants with HIE after asphyxia, suggesting S100 protein to be a complementary prognostic tool in predicting the risk for CP. A fetal/neonatal sheep model was developed, intended to reflect the clinical situation in newborn infants who had suffered a severe perinatal asphyxia. The model, incorporating the transition from fetal to neonatal life, was used to study early cerebral glucose metabolism with FDG-PET. The global CMRgl was significantly reduced in newborn lambs 4 hours after asphyxia induced by fetal umbilical cord occlusion.

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