Although this study presents novel findings concerning the brain regions that are most influenced by familial risk factors versus those associated with prenatal exposure to alcohol, the study limitations warrant discussion. The distribution of subjects by gender varied between the high and low-risk groups. Considering the underlying differences in the brain morphology of male and female subjects, testing for differences in male and female only samples was warranted but resulted in loss of subjects and associated power. Additionally, prenatal use of particular substances was not available for all subjects. Accordingly, VBM analyses involving use of covariates to control for specific prenatal exposures required the elimination of those subjects without this information (a total of 13 subjects) reducing the power of the analysis. This limitation was offset by the mixed model analysis performed using SPSS in which subjects missing a particular covariate are not dropped from the analysis. Accordingly, the analyses performed in SPSS did allow for inclusion of all subjects even those with missing covariates.
