Research Article: 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

Date Published: August 23, 2016

Publisher: Public Library of Science

Author(s): Amir Sariaslan, David J. Sharp, Brian M. D’Onofrio, Henrik Larsson, Seena Fazel, Phillipa J. Hay

Abstract: BackgroundTraumatic brain injury (TBI) is the leading cause of disability and mortality in children and young adults worldwide. It remains unclear, however, how TBI in childhood and adolescence is associated with adult mortality, psychiatric morbidity, and social outcomes.Methods and FindingsIn a Swedish birth cohort between 1973 and 1985 of 1,143,470 individuals, we identified all those who had sustained at least one TBI (n = 104,290 or 9.1%) up to age 25 y and their unaffected siblings (n = 68,268) using patient registers. We subsequently assessed these individuals for the following outcomes using multiple national registries: disability pension, specialist diagnoses of psychiatric disorders and psychiatric inpatient hospitalisation, premature mortality (before age 41 y), low educational attainment (not having achieved secondary school qualifications), and receiving means-tested welfare benefits. We used logistic and Cox regression models to quantify the association between TBI and specified adverse outcomes on the individual level. We further estimated population attributable fractions (PAF) for each outcome measure. We also compared differentially exposed siblings to account for unobserved genetic and environmental confounding. In addition to relative risk estimates, we examined absolute risks by calculating prevalence and Kaplan-Meier estimates. In complementary analyses, we tested whether the findings were moderated by injury severity, recurrence, and age at first injury (ages 0–4, 5–9, 6–10, 15–19, and 20–24 y).TBI exposure was associated with elevated risks of impaired adult functioning across all outcome measures. After a median follow-up period of 8 y from age 26 y, we found that TBI contributed to absolute risks of over 10% for specialist diagnoses of psychiatric disorders and low educational attainment, approximately 5% for disability pension, and 2% for premature mortality. The highest relative risks, adjusted for sex, birth year, and birth order, were found for psychiatric inpatient hospitalisation (adjusted relative risk [aRR] = 2.0; 95% CI: 1.9–2.0; 6,632 versus 37,095 events), disability pension (aRR = 1.8; 95% CI: 1.7–1.8; 4,691 versus 29,778 events), and premature mortality (aRR = 1.7; 95% CI: 1.6–1.9; 799 versus 4,695 events). These risks were only marginally attenuated when the comparisons were made with their unaffected siblings, which implies that the effects of TBI were consistent with a causal inference. A dose-response relationship was observed with injury severity. Injury recurrence was also associated with higher risks—in particular, for disability pension we found that recurrent TBI was associated with a 3-fold risk increase (aRR = 2.6; 95% CI: 2.4–2.8) compared to a single-episode TBI. Higher risks for all outcomes were observed for those who had sustained their first injury at an older age (ages 20–24 y) with more than 25% increase in relative risk across all outcomes compared to the youngest age group (ages 0–4 y). On the population level, TBI explained between 2%–6% of the variance in the examined outcomes.Using hospital data underestimates milder forms of TBI, but such misclassification bias suggests that the reported estimates are likely conservative. The sibling-comparison design accounts for unmeasured familial confounders shared by siblings, including half of their genes. Thus, residual genetic confounding remains a possibility but will unlikely alter our main findings, as associations were only marginally attenuated within families.ConclusionsGiven our findings, which indicate potentially causal effects between TBI exposure in childhood and later impairments across a range of health and social outcomes, age-sensitive clinical guidelines should be considered and preventive strategies should be targeted at children and adolescents.

Partial Text: The World Health Organization ranks traumatic brain injury (TBI) as the leading cause of both disability and mortality in individuals below the age of 45 y [1]. Conservative estimates from the United States indicate that TBI accounts for an annual combined average of approximately 848,000 hospital admissions and emergency room visits in individuals under the age of 25 y, the majority of which classified as concussions or mild TBI [2]. In England and Wales, it is estimated that between 462,200 and 700,000 children under 15 y of age attend emergency departments annually with head injury [3]. Similar findings have been reported in other high-income countries [4–6].

We identified 104,290 (9.1%) individuals that had sustained a TBI before age 25 y (Table 1). The overwhelming majority of these persons had suffered from mild TBIs (n = 80,676; 77.4%) and one in eight (n = 12,680; 12.2%) had experienced recurrent injuries. People with head injuries were, on average, more likely to be male and to have grown up in households characterised by a range of adverse psychosocial indicators (Table 1). Individuals who had sustained recurrent TBIs were, on average, approximately 2 y younger at their first injury than those who had sustained a single TBI (12.0 versus 13.8 y). Those who had sustained mild TBIs also tended to be younger at the time of their first injury than those who had sustained moderate to severe TBIs (12.2 versus 19.2 y).

In this population-based register study of over 1.1 million Swedish children, we examined the associations between TBI exposure, identified from inpatient and outpatient episodes, from birth up to age 25, and a range of adverse adult medical and social outcomes with public health implications. We followed the sample for up to 41 y, examined 683,860 siblings in addition to population controls, and the investigation was sufficiently powered to reliably explore the moderating effects of age categories at first injury. There were five principal findings. First, we found that being exposed to a mild TBI was associated with a range of adverse outcomes, including disability pension, psychiatric visits and inpatient hospitalisation, premature mortality, low educational attainment, and welfare recipiency. To provide more accurate estimates, we used unaffected siblings as comparisons, which demonstrated that although there was some familial confounding (shared genetic and childhood family environmental risks), we found that mild TBI was associated with 18%–52% increased risk of these outcomes. In particular, the risks were highest for psychiatric inpatient hospitalisation and disability pension.



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