Association of the APOE-ε4 allele with outcome of traumatic brain injury in children and youth: a meta-analysis and meta-regression

Objective To disentangle the temporal relationship between the APOE-epsilon 4 allele and outcomes of paediatric traumatic brain injury (TBI). Methods PubMed, EMBASE, Web of Science, MEDLINE, PsychINFO and HuGE Navigator Genopedia databases were searched from their inception up to January 2015 without language limitations. Included studies were analysed under a dominant genetic model to assess the association between the APOE-epsilon 4 allele and poor outcomes of paediatric TBI at 6 months. Metaregression was used to assess trends over time. Results Of the 325 initially identified records, 6 studies were selected and analysed based on inclusion/exclusion criteria. A total of 358 cases of paediatric TBI were included. 2 studies assessed outcomes at multiple time points ranging from 3 to 36 months; 4 studies assessed outcomes at a single time point (either 6 or 12 months). At 6 months, there is 2.36 (95% CI 1.26 to 4.42; p=0.007) times higher odds of poor outcome following TBI in children with at least one APOE-epsilon 4 allele, compared with the children without. Further, the adjusted odds suggested an increasing trend of 7% per month (95% CI -9 to 25; p=0.359). Conclusions This meta-analysis provides cumulative evidence that the APOE-epsilon 4 allele is important to the prognosis of paediatric TBI, but may have a different effect compared with adult TBI; moreover, this effect may be time dependent.