Long, Madison, Kar, Preeti, Forkert, Nils Daniel, Landman, Bennett Allan, Giesbrecht, Gerald F., Dewey, Deborah Margret, Gibbard, William Benton, Tortorelli, Christina, McMorris, Carly A., & Huo, Yuankai. (2025). Sex-specific relationships between gray matter volume and executive function in young children with and without prenatal alcohol exposure. Developmental Cognitive Neuroscience, 75, 101608. https://doi.org/10.1016/j.dcn.2025.101608
Sex differences in brain volume are well known across ages, but it is less clear how these differences relate to early cognitive abilities, especially in children exposed to alcohol before birth (prenatal alcohol exposure, PAE), which is a leading cause of developmental delays in North America. In this study, we examined how executive function—skills such as planning, attention, and self-control, measured by the BRIEF/BRIEF-P Global Executive Composite (GEC) and the Statue subtest of the NEPSY-II—relates to the volume of 36 brain regions in 169 children aged 2–8 years (37 with PAE; 534 total MRI scans). We found significant interactions between sex, alcohol exposure, and executive function in many regions: 22 regions for the GEC and 6 regions for the Statue. Unexposed boys generally showed negative associations between brain volume and executive function, while boys with PAE showed the opposite pattern. Unexposed girls showed strong positive associations, whereas girls with PAE showed weaker positive associations. In regions without these three-way interactions, we still observed sex differences: boys tended to show negative volume-executive function relationships and girls positive relationships, regardless of alcohol exposure. Overall, the findings suggest that boys with PAE and unexposed girls show more mature patterns of brain volume related to executive function compared to girls with PAE and unexposed boys. This study emphasizes the importance of considering sex when studying brain structure and cognitive development, especially in children affected by prenatal alcohol exposure.
Fig. 1. Box plot showing the distribution of scores for the Statue and the GEC. We found no significant differences in Statue scores between exposure groups. For the GEC, there was a significant difference (indicated by **) between the unexposed and PAE groups. Within exposure groups there were no sex differences in performance on executive function measures.