Traumatic brain injury (TBI) is the world’s leading cause of death and disability among young people and children, according to the World Health Organisation (WHO, 2006). There are an estimated 3 million new cases of paediatric TBI annually (Dewan et al., 2016).

There is some evidence to suggest that TBI sustained in youth is associated with long-term adverse outcomes such as:

• Psychiatric symptoms (Timonen et al., 2002)
• Criminality (McKinlay et al., 2014)
• Quality of life (Anderson et al., 2011)

However, more research is needed in this area to elucidate the impact of specific injury factors such as severity, age at injury and the effect of recurrent injury.

The current study aimed to explore the association between TBI and long-term adverse outcomes using population-based registers for the entire Swedish population (Sariaslan et al., 2016).

Methods

Participants included all Swedish children born between 1973 and 1985 who could be linked to their biological parents and neither died nor emigrated before the age of 26 years (n = 1,143,470). Data was derived from nationwide registries, including medical registers and census data.

Six main outcomes were assessed from the year the participants turned 26 years old until they experienced the outcome, died, migrated or the study itself ended. The outcomes were chosen as they relate to social or medical functioning and included:

1. Disability pension
2. Psychiatric visit
3. Psychiatric hospitalisation
4. Premature mortality (death before age 41 years)
5. Low educational level
6. Welfare recipiency

A wide range of covariates were adjusted for at different stages of the analysis such as sex, birth year, birth order, parental lifetime history of psychiatric morbidity and criminality, family income, parental education level and maternal marital status. For a subsample with available biological sibling data, a sibling-comparison model was fitted to account for unobserved familial confounders, such as environmental and genetic influences. Most analyses separated the TBI participants in terms of mild TBI and moderate-to-severe TBI.

Additional analyses were conducted on:

1. Participants who had a fall-related injury without a TBI diagnosis to examine potential effects of general injury-proneness;
2. Those who sustained more than one TBI compared to those with a single TBI episode; and
3. Participants stratified by age at first injury, i.e. 0-4 years, 5-9 years, 10-14 years, 15-19 years and 20-24 years.

The authors also calculated the population attributable fractions (PAF) for each outcome, this has been discussed in a previous blog.

Results

• There were 104,290 participants identified as having a TBI before age 25 years, the majority (77.4%) of these were mild TBIs.
• For all six outcomes, participants with a TBI had higher risk ratios that those without a TBI (see Table 1).

Table 1: Relative risks (RR) and corresponding 95% confidence intervals (CIs) for the associations

Notes:

• Model I: Full sample, adjusted for sex, birth order, and birth year
• Model II: Additional adjustments for individual and parental highest achieved education levels, parental income, parental lifetime criminal and psychiatric histories, and maternal single status
• Model III: Within-family estimates that are additionally adjusted for individual educational attainment at age 26 y.

• Mild TBI was associated with an 18% to 52% increased risk of the six outcomes
• There was a dose-response relationship with injury severity; those with moderate-to-severe injuries had much poorer outcomes. This was most notable for disability pension (RR = 2.06, 95% CI 1.78 to 2.38) and premature mortality (RR = 1.92, 95% CI 1.34 to 2.74)
• Recurrent TBIs were associated with increased risks compared with a single TBI event. In particular the risk for disability pension was 2-fold (RR = 2.22, 95% CI 1.88 to 2.63) for an individual with recurrent TBI compared to their sibling with a single TBI
• The PAFs (population attributable fractions) ranged from approximately 2% to 6% for TBI for the six outcomes
• The analysis on age at injury revealed that those who sustained their injury over the age of 15 years had greater risks of all outcomes. The most notable difference was for inpatient psychiatric hospitalisation, where the risk ratio for TBI exposure between ages 0-4 years was 1.24 (95% CI 1.15 to 1.34) and between ages 20-24 years was 2.47 (95% CI 2.37 to 2.58).

Conclusion

This study has a number of strengths including the large representative sample size, the use of data gathered from official registers and the well-controlled analyses. As the study was based on a whole population, selection bias is likely minimised and the findings have increased generalisability. The use of sibling-comparison design is an excellent method of accounting for unmeasurable familial confounders, while the inclusion of a fall-related non-TBI injury group allows for testing of general injury effects. Meanwhile the temporal relationship between the TBI exposure and the outcomes strengthens causal inference.

The authors note that one of the main limitations is that the use of medical records will naturally preclude cases of mild TBI where medical attention was not sought (Sariaslan et al., 2016). Nonetheless this is unlikely to have affected the main conclusions, although it may have caused a slight underestimation of the effects.

Overall this is a very useful and important study into the associations between TBI and adverse outcomes. Although the nature of epidemiological studies does not allow for an understanding of the interplay between certain exposures and outcomes, this large-scale investigation adds to a growing body of evidence associating TBI with the long-term outcomes.

Links

Primary paper

Sariaslan A, Sharp DJ, Onofrio BMD, Larsson H, Fazel S. (2016) Long-Term Outcomes Associated with Traumatic Brain Injury in Childhood and Adolescence : A Nationwide Swedish Cohort Study of a Wide Range of Medical and Social Outcomes. PLoS Medicine, 15–19. http://doi.org/10.1371/journal.pmed.1002103

Other references

Anderson, V., Brown, S., Newitt, H., & Hoile, H. (2011). Long-Term Outcome From Childhood Traumatic Brain Injury: Intellectual Ability, Personality, and Quality of Life. Neuropsychology, 25(2), 176–184. http://doi.org/10.1037/a0021217

Dewan, M. C., Mummareddy, N., Wellons, J. C., & Bonfield, C. M. (2016). The epidemiology of global pediatric traumatic brain injury: a qualitative review. World Neurosurgery. http://doi.org/10.1016/j.wneu.2016.03.045

McKinlay, A., Corrigan, J., Horwood, L. J., & Fergusson, D. M. (2014). Substance abuse and criminal activities following traumatic brain injury in childhood, adolescence, and early adulthood. The Journal of Head Trauma Rehabilitation, 29(6), 498–506. http://doi.org/10.1097/HTR.0000000000000001

Sariaslan, A., Sharp, D. J., Onofrio, B. M. D., Larsson, H., & Fazel, S. (2016). Long-Term Outcomes Associated with Traumatic Brain Injury in Childhood and Adolescence : A Nationwide Swedish Cohort Study of a Wide Range of Medical and Social Outcomes. PLoS Medicine, 15–19. http://doi.org/10.1371/journal.pmed.1002103

Timonen, M., Miettunen, J., Hakko, H., Zitting, P., Veijola, J., Von Wendt, L., & Räsänen, P. (2002). The association of preceding traumatic brain injury with mental disorders, alcoholism and criminality: The Northern Finland 1966 Birth Cohort Study. Psychiatry Research, 113, 217–226. http://doi.org/10.1016/S0165-1781(02)00269-X

WHO. (2006). Neurological Disorders: Public Health Challenges. World Health Organisation. Retrieved from http://www.who.int/mental_health/neurology/neurological_disorders_report_web.pdf

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