Prenatal alcohol exposure alters brain structure and neurocognitive outcomes for 6- to 7-year-old children in a South African birth cohort

Background: Several studies have demonstrated an association between prenatal alcohol exposure (PAE) and altered brain structure. However, more research is needed to understand how structural brain changes may influence neurocognitive performance in children with PAE at the age of school entry. We investigated the associations between PAE and cortical and subcortical gray matter morphology and whether PAE-related structural brain changes mediate the associations between PAE and neurocognitive outcomes in 6- to 7-year-old children. Methods: One hundred fifty-eight children (49 PAE, 109 unexposed controls; 46% female; mean age 76 ± 5 months) who participated in a brain imaging substudy of the population-based Drakenstein Child Health Study were included. The children had moderate-to-high PAE without other substance exposure, except prenatal tobacco exposure. T1-weighted brain structural scans were acquired using a 3T MRI scanner. General linear models and mediation analyses tested the associations of PAE with cortical and subcortical metrics and associated neurocognitive outcomes. Results: PAE was associated with a smaller total cortical surface area and had multivariate effects on regional cortical volume and surface area in the temporal lobe. The smaller volume and surface area of the left middle temporal gyrus mediated associations between PAE and neurocognitive outcomes for numeracy and mathematics and/or cognition and executive functioning. Findings persisted when adjusting for age, sex, maternal education, prenatal tobacco exposure, and, in volumetric and surface area models, intracranial volume. Conclusion: This study suggests that there is persistent altered brain structural development in children with PAE, consistent with previous findings in this cohort at infancy and age 2–3 years. Cortical changes in regions known to play a role in numeracy and semantic memory mediated associations between PAE and neurocognitive deficits, highlighting clinical relevance. Efforts to prevent PAE and improve neurocognitive development in children with PAE should be implemented as early as possible after birth.