Continuous normal voltage was found in 50% (n = 14), discontinuous normal voltage in 7.1% (n = 2), burst suppression in 32.1% (n = 9), continuous low voltage in 3.6% (n = 1) and flat trace in 7.1% (n = 2) of the infants. No differences in seizure activ-ity (Fisher’s exact test, p = 0.754) or aEEG background pat-tern (Fisher’s exact test, p = 0.355) were observed for the two Hb concentration groups. The aEEG background pat-terns in the deceased group were more often non-favour-able (burst suppression or flat trace; Fisher’s exact test, p = 0.010). These non-favourable patterns were associated with motor developmental delay in the surviving patients (χ2 test, p = 0.001). For neurodevelopment, non-favourable patterns showed a trend towards delay (χ2 test, p = 0.100).Neonatal OutcomeEighteen patients (36.7%) did not survive the neonatal period. Thirteen patients died within 72 h after birth, mainly due to acute multiple organ failure. The other 5 patients died following a decision to redirect care due to the expected serious long-term sequelae, based on clinical parameters (e.g. therapy-resistant convulsions) and/or extensive cerebral damage documented by MRI. The de-ceased patients had a significantly higher need for respi-ratory and circulatory support compared to the living pa-tients, but there was no difference in the presence of sei-zure activity.MRI AnalysisImaging was performed in 25 patients between day 2 and day 8 after birth (median: day 6). Five of the patients284 Neonatology 2016;109:282–288 Zonnenberg/Vermeulen/Rohaan/DOI: 10.1159/000443320van Weissenbruch/Groenendaal/de Vries. MRI findings in the total population abnormalities Values are given as n (%). WM = White matter.died, and MRI imaging was performed post-mortem in 3 of the patients. DWI images were available for 18 infants imaged during life. The clinical characteristics of infantswith an MRI were not significantly different compared to the total study population. In 3 deceased patients, MRI imaging was obtained c dpost-mortem. In 1 deceased patient, DWI (MRI obtained during life on day 6) showed few abnormalities in con- Fig. 1. MRI imaging. a, b MRI day 7: term born male with Apgar Values are given as n (%). WM = White matter; BGT = basal ganglia and thalami. Fisher’s exact test.. There was no difference in mortality between the two Hb concentration groups.Cerebellar damage was seen in 6 infants, in both Hb concentration groups (table 4). Haemorrhagic lesions were found in 3 infants, while ischaemic lesions were found in the other 3 infants.Neurodevelopmental OutcomeNeurodevelopmental test results were available in 20 of the 31 surviving patients (median age: 19 months, range: 14–35). The mean Z-score for neurodevelop-ment was 0.43 (SD 0.71). Only 1 patient (5%) was mild-ly delayed (Z-score: –1.08). The mean Z-score for mo-tor outcome was 0.58 (SD 0.81). One patient (5%) was mildly delayed (Z-score: –1.10). Unilateral spastic cere-bral palsy was diagnosed in 1 patient with haemor-rhagic cortical infarction. Of the 11 patients who were not formally tested, information was retrieved from the paediatrician, general practitioner or the parents. Cere-bral palsy was not diagnosed in any of these patients, but behavioural problems were reported in 1 patient. Information about outcome could not be retrieved in 2 patients.Thirteen of the 20 survivors with available MRI data were tested. The median age of testing was 24 months (range: 15–35). The mean Z-score for neurodevelopment was 0.37 (SD 0.76) and the mean Z-score for motor out-come was 0.67 (SD 0.88). No differences were found in neurodevelopmental and motor outcome between pa-tients with no/mild white matter abnormalities and pa-tients with moderate-to-severe white matter abnormal-ities.There were no differences between the two Hb con-centration groups for the neurodevelopmental outcome [mean Z-score: 0.33 (SD 0.79) and 0.73 (SD 0.59), respec-tively] and the motor outcome [mean Z-score: 0.62 (SD 0.88) and 0.49 (SD 0.62), respectively].DiscussionIn this retrospective study we were able to show that lesions in the basal ganglia and thalami, and especially in the white matter, are common findings in infants with severe neonatal anaemia.Cerebral damage has been suggested to be caused by several pathophysiological mechanisms. In full-term in-fants, the deep grey matter nuclei are probably affected after an acute hypoxic-ischaemic insult due to changes in brain maturation and increased metabolic demands [1]. White matter injury is also found in full-term infants and is considered to be due to more prolonged and repetitive hypoxic-ischaemic events. A combination of deep grey matter damage and white matter lesions can also be found [2]. We hypothesize that the mechanisms that cause bas-al ganglia and white matter injury following severe anae-mia might be similar to the mechanisms responsible for cerebral injury in full-term infants with perinatal asphyx-ia due to other causes. White matter injury has been de-scribed in animals as well as in humans after moderate prolonged foetal or neonatal asphyxia, as well as after neonatal hypoglycaemia [3, 4]. It is important to note that a substantial percentage (31%) of our anaemic patients also had a period of hypoglycaemia. The mechanism of injury due to hypoglycaemia is still unclear, although it has been hypothesized that it is caused by increased re-gional cerebral blood flow during hypoglycaemia with a subsequent reduction in regional glucose uptake [3].Even more interesting are the clinical implications of these findings. MRI is a well-established method to as-sess brain injury in infants suffering from perinatal as-phyxia, and these findings are closely related to later neurodevelopmental outcome [5–11]. Data on the long-term outcome of patients with severe acute anaemia combined with a less severe component of perinatal as-phyxia are still limited. It is of interest that early neuro-developmental and motor outcomes in the first 2 years of life in the survivors is favourable. In the absence of damage in the thalamus and basal ganglia, neonatal anaemia itself does not have a