Kim Annink

115 The papez circuit and school-age outcome in HIE INTRODUCTION Infants with hypoxic-ischemic encephalopathy (HIE) due to presumed perinatal asphyxia are at risk for death, motor problems, cognitive and memory deficits, behavioral problems and epilepsy (1,2). Infants with moderate to severe HIE are treated with whole body hypothermia, which has shown to improve 18-24 month survival without neurological disabilities (1,3,4). However, knowledge about the effect of therapeutic hypothermia on neurological outcome in childhood is limited. Therapeutic hypothermia improves survival and reduces cerebral palsy (CP) and epilepsy at school-age (5,6), but a considerable number of the children treated with hypothermia still has neurocognitive problems at school-age (5,7). To understand and potentially improve neurodevelopmental outcome in these children, it is important to elucidate which brain structures contribute to these long-term problems. With regards to cognitive function, injury to the hippocampus is associated with a lower intelligence quotient (IQ) and memory scores in children with HIE (8,9). The hippocampus is part of the Papez circuit, which further includes the mammillary bodies (MB), fornix and anterior thalamus. It was recently demonstrated that the MB are often affected following HIE (10). Similar to the hippocampus, MB are known to be important for memory function (11). Therefore, our primary aim was to investigate the association between injury to the Papez circuit, brain volumes, white matter integrity at 10 years of age and neurodevelopmental outcome in children with a history of HIE with and without therapeutic hypothermia. The secondary aim was to assess neurodevelopmental outcome in 10-year-old children with HIE treated with and without therapeutic hypothermia. METHODS Study population For this observational study, children were eligible if they: 1) were born after a gestational age ≥36 weeks, 2) had been admitted to the neonatal intensive care unit of the UMC Utrecht or Isala Clinics between 2006 and 2009 because of acute perinatal asphyxia, 3) (would have) qualified for therapeutic hypothermia and 4) had reached the age of 10 years. Exclusion criteria were congenital brain abnormalities and/or other (chromosomal/metabolic) anomalies, acquired brain injury due to trauma or infection, severe cerebral palsy making magnetic resonance imaging (MRI) 6