The impact of prenatal alcohol and tobacco exposure on white matter integrity in 8–12-year-old children

The combined impact of prenatal alcohol exposure (PAE) and prenatal tobacco exposure (PTE) on white-matter integrity in pre-adolescence is poorly understood. We aimed to explore white-matter integrity in children aged 8- to 12-years with PAE and/or PTE versus those without (controls, CON). Here, 410 children (CON: n = 84; PAE: n = 94; PTE: n = 67; PAE + PTE: n = 165) underwent diffusion tensor MRI as part of the Safe Passage Study, a cohort based in Cape Town, South Africa. Linear regression modeling was used to investigate the main and interaction effects of PAE and PTE. There were disordinal PAE × PTE interactions on right-cerebral-peduncle mean, axial, and radial diffusivity: Individuals with PAE and PTE had higher mean and axial diffusivity than those with either exposure on its own, but similar to those with neither. In children with PAE, there were associations with altered axial diffusivity among those exposed during the first trimester and mean, axial, and radial diffusivity in those exposed during the second trimester in commissural, association, and projection tracts. Further, there were PTE associations with fractional anisotropy and radial diffusivity in projection tracts among those exposed mainly during the second trimester. These results support previous research in children with PAE and add to the PTE literature, highlighting potentially lasting impact on axonal and myelin microstructural development, which are important for motor, sensory, cognitive, and behavioral functions. Our results suggest sensitivity to the timing of exposure of PAE and PTE, particularly during the first and second trimesters of pregnancy.