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

. 2025 May;49(5):1028-1041.

doi: 10.1111/acer.70048. Epub 2025 Apr 6.

Shantanu H Joshi 2 3, Jessica E Ringshaw 1 4 5, Layla Bradford 1, Annerine Roos 4 6, Catherine J Wedderburn 1 4, Nadia Hoffman 4 6, Tiffany Burd 7 8, Katherine L Narr 2 9, Roger P Woods 2 9 10 11, Heather J Zar 7 8, Dan J Stein 4 6 12, Kirsten A Donald 1 4

Affiliations

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

Chanellé J Hendrikse et al. Alcohol Clin Exp Res (Hoboken). 2025 May.

Abstract

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.

Keywords: early learning outcomes; neurodevelopment; prenatal alcohol exposure; structural magnetic resonance imaging.

© 2025 The Author(s). Alcohol, Clinical and Experimental Research published by Wiley Periodicals LLC on behalf of Research Society on Alcohol.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

FIGURE 1

FIGURE 1

Flowchart of participation in the Drakenstein Child Health Study (DCHS).

FIGURE 2

FIGURE 2

Illustration of the simple mediation model.

FIGURE 3

FIGURE 3

Cortical regions of the Desikan–Killiany atlas (Desikan et al., 2006) with significant univariate prenatal alcohol exposure (PAE) effects in the main (Table 3; Section PAE effects on regional cortical metrics) and exploratory analyses (Table S1; Section Exploratory univariate PAE effects on individual ROIs). All effects are illustrated on the right hemisphere.

FIGURE 4

FIGURE 4

Illustration of the mediating role of surface area of the left middle temporal gyrus in the associations between prenatal alcohol exposure (PAE) and the early learning outcomes measure (ELOM) numeracy and mathematics (results indicated in orange rectangles) and cognition and executive functioning (results indicated in blue rectangles) subscales.

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