Kim Annink

74 Chapter 4 METHODS Study population We included (near-) term infants (36 until 42 weeks of gestational age) with HIE who were treated with hypothermia in the University Medical Center Utrecht between January 2008 and July 2014, who had at least one CUS on day one and a second CUS between day three and seven after birth. An additional inclusion criterion was the availability of outcome data, either death or a neurodevelopmental follow-up examination at the age of two years. We excluded infants with metabolic or genetic abnormalities. We used this cohort to create the scoring system (cohort I). A different cohort with similar clinical characteristics, born in the Erasmus Medical Center in Rotterdam, with at least one CUS between day three and seven and available outcome data was used to validate the scoring system (cohort II). The same inclusion and exclusion criteria applied to this cohort. In both cohorts the CUS scans were part of standard clinical care. The scans were conducted by trained neonatologists, fellows in neonatology and physician assistants with different levels of experience in CUS. In cohort I CUS were performed using an ultrasound machine from Toshiba (Medical System Corporation, Tokyo, Japan) and in cohort II from Esaote (Genova, Italy). Convex 5-10 MHz and linear 15-18 MHz probes were used in both cohorts. The Ethical Committee of the University Medical Center Utrecht approved this retrospective study and waived the requirement to obtain written informed consent for this study analyzing pseudonymized data. Development of the CUS scoring system We searched the literature for possible CUS items to include in the scoring system. The relevance of all these items was discussed by a group of experts including neonatologists and a pediatric neuroradiologist, all with many years of experience in CUS (JD, LdV, FG, PG, ML). Items were categorized into normal-mild, moderate and severe or into absent and present. The same group of experts reached consensus on the definitions of the different categories. For examples of the items see Figure 1 and for definitions see Table 1. Additional antenatally acquired pathology was also scored i.e. porencephaly and atrophy.