Kim Annink

96 Chapter 5 METHODS Study population This study is a sub-study of a larger follow-up cohort, other results of this cohort have been previously published by van Handel et al. and van Kooij et al. (10,11,17,18). All participants were born at term (37 to 42 weeks of gestation) between 1993 and 1997 in the Wilhelmina Children’s Hospital with HIE following presumed perinatal asphyxia. Perinatal asphyxia was diagnosed when at least three of the following criteria were met: signs of fetal distress (late decelerations on fetal monitoring or meconium-staining amniotic fluid), Apgar score below seven at 5 minutes postpartum, arterial umbilical pH <7.10, delayed onset of spontaneous respiration or multi-organ failure (10,11). Exclusion criteria were small for gestational age, neurological malformations, congenital or chronic diseases influencing outcome, maternal substance use during pregnancy and focal damage with total loss of hippocampal volume. Children with HIE were divided in two groups. Mild HIE (HIE1) was defined as recovery within 24 hours and a normal electroencephalography (EEG), corresponding with Sarnat stage 1 (3). Moderate HIE (HIE2) was defined as no recovery within 24 hours and an abnormal EEG, the presence of neonatal seizures, corresponding with Sarnat stage 2 (3). Infants with severe HIE were not included in this study. All infants were born and admitted to our level three neonatal intensive care unit before therapeutic hypothermia became standard of care. Children with the same sex and age, attending regular schools without any special help, were invited as controls. Parents provided details on the perinatal history to exclude children with complications around delivery or referral to a hospital in the first month after birth. Informed parental consent and child assent were obtained for all participants according to the Declaration of Helsinki. The Ethical Committee of the University Medical Center Utrecht approved the study. MRI and volumetric measurements Magnetic resonance imaging (MRI) was obtained between the age of 9 and 10 years, using a 1.5 Tesla Philips system. Brain segmentation was performed using coronal 3D-T1-weighted images (TR: 30ms; TE: 4.6ms, slice thickness: 1.5mm). The left and