In this study, we have shown that both children with PVHI and children with PAIS have below average cognitive ability at school age and some weaknesses in other specific cognitive domains. While a neurodevelopmental delay was already present in infancy in participants with PVHI, children with PAIS showed a significant decline in neurodevelopmental outcome over time.
Periventricular haemorrhagic infarction
Children with PVHI already showed performance outside the normal range in infancy and they demonstrated no further decline when tested at school age. At school age, children with PVHI showed an average FSIQ of 86. While this was below that of typically developing children, one should take into account that the cognitive performance of these children might be further complicated by their preterm birth, which is a known risk factor for lower IQ scores. Several studies have shown that IQ scores of preterm-born children are 5 to 10 points lower than in a term-born comparison group. Children with PVHI, therefore, seem to perform only slightly worse than preterm children without PVHI. This is in line with the work of Roze et al., on cognitive function in infants with PVHI, who found a mean FSIQ of 83 in these children. Bassan et al. also found that half of PVHI survivors developed significant cognitive abnormalities.
Although previous studies reported impairments in verbal memory[7, 22] and behavioural problems (especially impairments in executive functions),[22, 23] we could not confirm this. Preterm birth is known to affect visuomotor processes,[24, 25] which is in line with our findings. Similarly, attention and concentration deficits are more frequently observed in preterm children.[26, 27] It is unknown, however, whether these deficits are exacerbated by the presence of a PVHI. Finally, we found shorter reaction times in response to visual stimuli in children with PVHI. We hypothesize that the increased use of electronic devices may play a role in this finding.
Although we were not able to perform a linear regression analysis in the PVHI group, our data suggest that development of PHVD had a negative effect on cognitive performance. Posthaemorrhagic ventricular dilatation is a frequently observed complication of an intraventricular haemorrhage. Although it is not necessarily associated with an unfavourable outcome, even when neurosurgical intervention is required, several studies have shown that PHVD in the presence of PVHI results in lower cognitive performance.[7, 28]
The observed relation between the level of maternal education and FSIQ has been reported before.[29, 30] Possible explanations include a higher quality of child care, cognitive stimulation, and the use of follow-up services. Moreover, IQ differences in children may be genetically caused by differences in the maternal IQ.
Perinatal arterial ischaemic stroke
The reported cognitive outcome after PAIS has been variable. Some studies have reported a favourable long-term outcome, whereas other studies have reported lower intellectual abilities at school age.[8, 32-34] Ricci et al. found normal cognitive outcome in children with PAIS, but the majority of the participants were preschool children at the time of assessment. Ballantyne et al. reported longitudinal measurements and found a normal cognitive function at school age, but found lower IQ scores in children who developed epilepsy. The decline in function over time, as found in our study, is in line with the study of Westmacott et al., who found that the performance of children with PAIS did not differ from the normative sample of preschool children, but when compared with the normative sample of school-age children, performance was significantly lower for overall intellectual ability. This does not reflect a loss of skills, but, rather, slower gains over time and difficulty with higher-level cognitive skills compared with healthy peers. The reported normal performance in other studies might reflect differences in the duration of follow-up, which may have been too short to detect late-emerging deficits. This suggests that a continued follow-up of these children until they are attending school is important to understand how these children cope with more academic tasks.
Previous studies have reported specific language impairments after PAIS.[31, 35] In contrast to these studies, we did not find impairments in word comprehension, but we did find poor visual–motor integration. Talib et al. did not find impairments in visual–motor integration, but this may also be attributed to the short duration of their follow-up.
Linear regression showed that both involvement of the basal ganglia and thalami and development of postneonatal epilepsy were associated with lower FSIQ scores. Development of postneonatal epilepsy has previously been associated with a decline in cognitive function. It remains uncertain, however, what the underlying mechanism is, as both epilepsy and the antiepileptic drugs may play a role. We were unable to differentiate between these two factors, as all children with epilepsy used antiepileptic drugs. Thalamic injury is increasingly being associated with poor cognitive outcome, in both preterm and term infants, possibly owing to the regulatory role of the thalamus in information transmission to the cortex and between cortical areas.[37-39] It has been extensively associated with cognitive deficits in adult stroke, but ours is the first study that associates thalamic injury with lower cognitive scores after PAIS.
This study has some limitations which need to be addressed. First, the comparison of performance across time was complicated by the use of a neurodevelopmental measurement and an intelligence test at school age. After discharge from the neonatal intensive care unit, all children were seen at the neonatal clinic for routine follow-up. In this setting, the Griffiths Mental Developmental Scale provided a useful tool to evaluate the child's development in a limited amount of time. A second potential limitation is that, although we studied a relatively large group with perinatal brain injury, a larger group would allow more extensive statistical analyses, potentially identifying other factors associated with outcome. Another possible limitation is that the age range at neuropsychological assessment was very wide (6–20y). We controlled for this using age-appropriate norms and test versions. All the children in our study were attending school, but it is important to understand how they cope with more academic tasks. Finally, we did not study the visual performance of all children, though prematurity and both PAIS and PVHI are associated with visual disorders, including retinopathy of prematurity, visual field defects, and cerebral visual impairment. Even though visual disorders may also affect the neuropsychological test results, the presence of such disorders seemed low in the present study, as a parental questionnaire reported visual deficits in only three children (one quadrantanopia, two hemianopia) and screening for retinopathy of prematurity in 22 out of 28 preterm-born infants displayed a grade I retinopathy in only one infant.
In conclusion, children with PVHI or PAIS reported in this study showed a below average performance when tested at school age. Their performance was, however, not severely affected, as it fell within 1SD of the healthy population and a majority (76%) still attended mainstream education. While motor outcome can be reliably predicted using conventional neonatal MRI, prediction of cognitive outcome remains challenging, as only development of PHVD after PVHI, and basal ganglia and thalami involvement and development of postneonatal epilepsy after PAIS, were associated with poorer cognitive outcome.