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ObjectiveThe aim of this pilot study was to assess associations of prenatal alcohol exposure (PAE), prenatal tobacco exposure (PTE), and their interaction and quantity on subsequent cortical and subcortical measures at age 6 years.MethodsMothers with varying levels of alcohol and tobacco exposure at different trimesters during pregnancy were approached when their children (born participating in the Safe Passage Study) were approximately 6 years old. 72 mothers agreed to participate, and 51 children completed brain magnetic resonance imaging (MRI). Brain regions of interest (ROIs) that were significantly associated prior to multiple comparison testing, were examined for associations related to exposure quantity, frequency, and timing (QFT), to explore how patterns of PAE and PTE influence brain outcomes in children. Linear regression was used to identify associations between PAE, PTE, and their interaction with cortical (n = 68 ROIs) and subcortical (n = 40 ROIs) measures.ResultsPrior to correction for multiple comparison testing, both PAE and PTE, as well as their interaction, were associated with a range of cortical and subcortical measures. However, none of these findings survived correction for multiple comparisons. Nevertheless, when exploring quantity of PAE, the total amount of standard drinks consumed during pregnancy and the average number of drinks per drinking day were positively associated with cortical volume in the right fusiform gyrus.ConclusionThese trend results in this pilot study provide preliminary evidence that PAE impacts brain development in unique ways from PTE, and their interactive co-exposure is not a straight forward synergistic or additive effect on the brain.