PREMORBID DISABILITY

We identified 115 children among the 151 survivors in whom prior neurocognitive morbidity was considered unlikely by the stringent criteria above. There was no significant difference in mean age between this group and the remainder of the 278 child cohort (p > 0.8; unpaired t test), but there were significant differences in the frequencies of specific aetiologies between these prior normal children and the full cohort (see table 2). Relative to the series as a whole (deaths plus other survivors), intoxication and unknown aetiologies were over represented, and infection under represented in the prior normal survivors group (p < 0.0001; χ²  = 48.7; df  = 7; table 2).

AGE AT INSULT AND COGNITIVE OUTCOMES

We analysed the 115 children in the prior normal subset for age at insult effects. No relation was evident between age at insult and final CQ for the 115 children as a whole (Pearson'sr = 0.03; p > 0.5).

Separate analyses were performed within each aetiological group across the entire age range. We found no significant correlation between age at insult and final CQ, nor were there significant gender effects.

TIME COURSE OF RECOVERY AFTER NTC

Cognitive data were available at both early and late time points (nominally six weeks and 12 months post-insult) for 82 of the 115 prior normal children. This gave an opportunity to assess the recovery at two time points. For a small number of children who crossed age limits for the use of the cognitive outcome instruments between first and second assessments, we needed to use a different instrument at each time point. Bayley, WPPSI, or WISC data were consolidated into a single all age CQ (see Methods). Across the whole age range, there was no correlation between age (treated as a continuous variable) and change in CQ between early and late time points (ΔCQ). However, we noted a trend for younger children not to show the improvement between early and late time points shown by older children. For children over 24 months at insult, mean ΔCQ was significantly greater than zero (mean +4.1; 95% confidence interval (CI) 0.9 to 7.4; p < 0.05), implying some spontaneous recovery between early and late time points. This was not the case for children less than 24 months at insult who showed a mean ΔCQ of −3.3 (95% CI −9.0 to +2.3; p > 0.2), implying no significant spontaneous recovery in cognitive abilities (see fig 1 and Discussion).

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Figure 1

Effect of age at injury on difference in CQ between early (six week) and late (12 month) time points (ΔCQ).

Subgroup analysis by aetiological category showed a significant relation between ΔCQ and age at insult for the epilepsy group (Spearman r corrected for ties 0.61; two tailed p < 0.05). Previously normal children experiencing an episode of NTC caused by epilepsy under the age of 12 months showed a mean fall in CQ in the interval six weeks to 12 months insult of −12.4 (SEM 2.0) points (p < 0.05). This fall is additional to the morbidity already evident six weeks after insult.

ADAPTIVE BEHAVIOUR

Of 151 late survivors, 141 had neurological and cognitive assessments. Ninety three children showed no impairment in any assessed domain. These children were thus assigned an assumed normal range VABS adaptive behaviour composite score category. A remaining 48 were eligible for full Vineland assessment, of whom we assessed 33 (see table 3). We found significant morbidity in the adaptive behaviour domain, with 13% of survivors showing an adaptive behaviour composite score more than two standard deviations below the population mean (that is, in the moderate or severe categories as described above). Among the prior normals, eight of 115 children (7.0%) showed this degree of disability.

There was a significant association between the presence of significant disability after an episode of NTC (defined as adaptive behaviour of less than −2SD) and the presence of premorbid disability. Children identified as having significant disabilities were under represented in the prior normal group (table 3; p < 0.0001, Fisher exact test). This suggests that some of the adaptive behaviour morbidity seen in the series as a whole was indeed of premorbid origin (see Discussion).

MEASUREMENT OF IMPACT OF DISABILITY

The quantification of neurological morbidity is particularly challenging in children. Adult measures of acquired neurological disability such as the Glasgow Outcome Scale and the Disability Rating Scale14-16 compare outcome to a baseline of mature independent adult functioning. In contrast, paediatric measures must relate to age dependent expectations of independence. Furthermore the neurological, cognitive, and other aspects of physiological child development resume after a neurological insult and can be modified as a consequence of its occurrence: thus the shortfall between current functional status and the changing age dependent standards of “normality” is dynamic. There is an additional dynamic relation between the component parts of the total morbidity burden. The relative contributions of the physical, behavioural, and cognitive subdomains to overall morbidity are highly variable. These complex interrelations hamper the creation of unidimensional global morbidity scores.

The conceptual framework of the World Health Organisation International Classification of Impairment, Disability, and Handicap (ICIDH)17 is widely used. “Impairments” relate to limitations of function at the level of an individual organ while “disabilities” refer to limitations at the level of the individual's ability to function. Limitations in the child's ability to fulfil meaningful roles in society are designated within the WHO classification under the rubric of “handicap”, although this remains unsatisfactory both as a term and a concept,18 and is replaced by the concept of “participation” in the forthcoming revision of the ICIDH. The neurological and cognitive/behavioural assessments we used can be regarded as measures of impairment or disability. They share with other measures of impairment the advantage of relative ease of assessment. The logistical implications of performing Vineland assessments in all survivors obliged us to use measures of impairment as a screening device, making the implicit assumption that “handicap” (as measured by the Vineland score) would not occur in the absence of detectable impairment in one or more of the assessed domains. We acknowledge the limitations of this approach. Additionally, the limitations of the Vineland instrument in measuring the full impact of an episode of NTC are recognised. For example, the Vineland instrument is an entirely “within the child” measure, that does not attempt to capture the effects of a child's illness on wider family function.

BURDEN OF DISABILITY CAUSED BY NTC

While no prior data were available, it seemed probable that some children with pre-existing neurodisabilities might be at increased risk for NTC of particular aetiologies. Table 2 confirms an association between certain aetiologies of NTC and the presence or otherwise of premorbid disability. While it was not possible to systematically collect data on premorbid functioning, we attempted to identify a cohort in whom there were no prior suspicions of particular neurocognitive difficulties.

The statistically significant association between diminished adaptive behaviour and the suspicion of premorbid disability (table 3 and Results) suggests that some of the adaptive behaviour morbidity seen in the series as a whole was indeed of premorbid origin. Nevertheless at least 7% of the stringently defined prior normal group acquired moderate or severe levels of adaptive disability, defined as VABS scores less than two standard deviations below population mean, as a direct result of their NTC. This figure excludes any disability among the group lost to follow up (table 3). Additionally, in this selected population of “prior normal” children the prior distribution of adaptive behaviour scores might be expected to be shifted to the right (more capable) relative to the full “normal” population. Thus this figure of 7% is an underestimate of the prevalence rate of moderate or severe disability that can be directly attributed to NTC.

AGE AT INJURY EFFECTS

It is now recognised that traumatic brain injury is an event that will alter the entire subsequent developmental trajectory for a child. As a child injured in the early years of life attempts to acquire new skills, the apparently subtle deficits in new learning that are often selectively impaired in TBI may compound over the years into a significant late morbidity.7 This study provides evidence for limited age at insult effects in NTC: they are obscured to a considerable extent by differences in the pathophysiology of the NTC between aetiological groups. Children recovering from NTC are probably a more heterogeneous group than their traumatically injured counterparts. Nevertheless it is clear that very young children (under 24 months of age at insult) are a group with a more guarded prognosis, showing little or no catch up over time after NTC (fig 1). This may reflect a limited repertoire of pre-existing skills on which to draw in making a recovery.

The relative weakness of the age related effects seen here may in part reflect the use of global IQ scores rather than specific tests of attentional, executive, and other functions that may be more selectively impaired following acquired brain injury. Additionally, effects may be obscured by the need to use different instruments within different age bands: it is not clear that the Bayley Mental Developmental Index is measuring precisely the same processes in infants that the WISC reflects in older children

Age related effects on outcome can reflect several different mechanisms.2 Our study, assessing at a standard interval since insult, highlights age at injury relations. These may reflect the consequences of selective damage to brain regions undergoing active development at the time of injury.2 Additionally, the association of particular aetiologies with age1 will be important. Within the various aetiological categories, significant age at insult effects were only evident within the epilepsy group, with younger children having a poorer outlook. Epileptic encephalopathies presenting in early childhood are known to have a poorer long term outlook.19

By comparison, time since insult analyses may highlight the consequences of damage to structures required for skill acquisition. Cross sectional studies have shown that cognitive weaknesses among children with early brain insults caused by hydrocephalus20 or myelomeningocoele21 are more evident in older than younger children. Figure 1 begins to show this effect longitudinally in children following NTC. It will be important to reassess this cohort at later timepoints.

We have highlighted significant morbidity following NTC in childhood, and provided further support for the hypothesis of increased vulnerability of very young brains to cognitive sequelae of acquired brain injury.