In the introduction section of this review, problems were mentioned with regard to the comparability of different outcome studies of NE. Even after careful selection on the basis of predetermined criteria, comparing studies remained difficult. The main reason for this was the way test results were presented. In many cases, outcome of the children was reported in two or more categories, e.g., normal/mildly delayed/abnormal. One of the problems that arise due to such categorization, is the subjectivity involved in determining the cut-off points of the categories. Often, these cut-off points seemed to be chosen arbitrarily or not justified at all. Another issue that adds to this problem is the use of different tests of development, cognitive ability or behavioral problems. One can hardly compare, for example, the proportions of children with developmental delay in two studies when these are represented by a score below 85 on the Bayley Scales of Infant Development in one of the studies and by a score below 70 on the Griffiths Mental Developmental Scales in the other. To enable readers to compare studies, results of significance testing between subgroups of children with NE and comparison groups were added to the tables whenever available.
Children with a history of NE who suffer from CP at the age of 12 months are often also severely developmentally delayed. Estimates vary between 77% [12
] and 90% [24
]. Of the children without CP, those with mild NE have an excellent prognosis. Their intelligence, educational achievement and neuropsychological functions are comparable to healthy peers at least until middle childhood.
Children with severe NE appear to be impaired in every cognitive domain. They are less intelligent and perform worse at school and at neuropsychological tests than both healthy controls and children with mild or moderate NE.
As was expected, the children with moderate NE seem to form the most heterogeneous group. In general, these children are significantly less intelligent than children with mild NE and healthy peers, but their scores are still in the average range. And although these children are equally ready to go to school as other children at the age of 5.5 years, when measured in middle childhood, they perform less well in the domains reading, spelling and mathematics. On the basis of these results, it is possible that children with moderate NE fall behind in school, but do not show clear deficits at standardized testing. Another issue is raised by the relatively broad range of performance of children with moderate NE. Calculating mean IQ scores masks individual differences, which are large in groups of children with moderate NE. Therefore, means do not describe this group well, and it would be more informative to look at the distribution of scores. The description of neuropsychological functions in this review is based on six studies, in which five different tests were used in five different samples of children with moderate NE. These studies do not provide sufficient and comparable data to draw reliable conclusions about patterns of neuropsychological strengths and difficulties. The heterogeneous nature of the group of children with moderate NE raises the question whether these children really form one group. Marlow et al. [32
] divided a group of children with moderate NE according to the severity of the symptoms of the NE. The group with the least severe neonatal symptoms showed a few discrete neuropsychological difficulties, but was more intelligent and performed better in school than the group with the most severe neonatal symptoms. Marlow suggested a dose-response effect of hypoxia within this group with moderate NE. This idea of a continuum of casualty with regard to morbidity has already been proposed by Low [29
]. He suggested a theory of a critical threshold of asphyxia beyond which brain damage occurs. Beyond this threshold, a spectrum of minor and major deficits would occur. So, although the classification system of Sarnat [50
] appears to be very useful for the prediction of the outcome of children with mild or severe NE, in case of moderate NE this qualitative system lacks predictive power. Future research should therefore focus on developing a reliable, more gradual model of prediction.
Another issue regarding prediction of outcome after NE also mainly concerns moderately affected children. It is still unclear whether NE has a general effect on intellectual abilities or leads to specific patterns of cognitive strengths and difficulties. This review shows that systematic, detailed research of neuropsychological function is still scarce. A few case reports, which are not included in this review, have shown specific impairments in episodic memory (memory for events), with relatively intact semantic memory (memory for facts) [21
]. However, these findings, which were based on small numbers of children, do not justify generalization to all children with NE and should therefore be replicated in larger, well-defined samples.
The introduction section of this review referred to possible associations between brain areas that are vulnerable to perinatal hypoxia and psychopathology, such as ADHD and autism. Long-term behavioral outcome of survivors of NE has received very little attention compared to neurological outcome and general intellectual ability. Only a few studies looked at the behavioral consequences of NE. Those studies found elevated rates of hyperactivity and autism in children with moderate NE. Evidence of hyperactivity and impulsive behavior has also been found in animal studies of PA [1
]. These findings suggest that, in addition to cognitive impairment, children with NE could be at risk of developing behavioral problems. Because of the clinical implications this would have, future research should include behavioral monitoring of all children with NE.
Long-term follow-up of children with NE has been advocated before, including the optimal ages of assessment of specific functions [48
]. Recommendations include assessment of general cognitive and adaptive behavioral functioning at preschool age, and, in some cases, school achievement tests and a neuropsychological screening at school age. The authors of this review would like to go one step further in recommending standard screening for behavioral problems in all children with NE, regardless of their level of cognitive functioning. In addition, detailed neuropsychological assessment is recommended especially in all children with moderate NE.
From this review it is concluded that general intellectual, educational and neuropsychological outcomes are consistently positive for children with mild NE and negative for severely affected children. However, children with moderate NE form a more heterogeneous group with respect to outcome. On average, intelligence scores are below those of children with mild NE and age-matched peers, but within the normal range. Difficulties have been found in the domains reading, spelling and arithmetic/mathematics. So far, neuropsychological functioning of children with NE has received relatively little attention. The studies that were selected for this review have yielded ambiguous results in children with moderate NE. A few studies suggest elevated rates of hyperactivity in children with moderate NE and autism in children with moderate and severe NE. Therefore, behavioral monitoring is required for all children with NE. In addition, systematic, detailed neuropsychological examination is needed especially for children with moderate NE.