The Effects of Prenatal Alcohol Exposure on Structural Brain Connectivity and Early Language Skills in a South African Birth Cohort

Mohammad Ghasoub^{1

2}, Chloe Scholten^{1

2}, Bryce Geeraert^{1

2

3}, Xiangyu Long^{1

2

3}, Shantanu Joshi^{4

5}, Catherine J Wedderburn^{6

7}, Annerine Roos^{7

8}, Sivenesi Subramoney⁶, Nadia Hoffman⁸, Katherine Narr^{4

9}, Roger Woods^{4

9

10

11}, Heather J Zar^{12

13}, Dan J Stein^{7

8

14}, Kirsten Donald^{6

7}, Catherine Lebel^{1

2

3}

Affiliations

¹ Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Canada.
² Hotchkiss Brain Institute, University of Calgary, Calgary, Canada.
³ Department of Radiology, Cumming School of Medicine, University of Calgary, Calgary, Canada.
⁴ Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, University of California, Los Angeles, Los Angeles, CA, USA.
⁵ Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA, USA.
⁶ Division of Developmental Paediatrics, Department of Paediatrics and Child Health, Red Cross Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa.
⁷ Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
⁸ Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa.
⁹ Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA, USA.
¹⁰ Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA, USA.
¹¹ David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
¹² Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa.
¹³ South African Medical Research Council (SAMRC), Unit on Child and Adolescent Health, University of Cape Town, Cape Town, South Africa.
¹⁴ South African Medical Research Council (SAMRC), Unit on Risk and Resilience in Mental Disorders, University of Cape Town, Cape Town, South Africa.

PMID: 40201449
PMCID: PMC11977823
DOI: 10.1162/nol_a_00161

The Effects of Prenatal Alcohol Exposure on Structural Brain Connectivity and Early Language Skills in a South African Birth Cohort

Mohammad Ghasoub et al. Neurobiol Lang (Camb). 2025.

. 2025 Apr 2:6:nol_a_00161.

doi: 10.1162/nol_a_00161. eCollection 2025.

Authors

Affiliations

¹ Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Canada.
² Hotchkiss Brain Institute, University of Calgary, Calgary, Canada.
³ Department of Radiology, Cumming School of Medicine, University of Calgary, Calgary, Canada.
⁴ Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, University of California, Los Angeles, Los Angeles, CA, USA.
⁵ Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA, USA.
⁶ Division of Developmental Paediatrics, Department of Paediatrics and Child Health, Red Cross Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa.
⁷ Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
⁸ Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa.
⁹ Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA, USA.
¹⁰ Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA, USA.
¹¹ David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
¹² Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa.
¹³ South African Medical Research Council (SAMRC), Unit on Child and Adolescent Health, University of Cape Town, Cape Town, South Africa.
¹⁴ South African Medical Research Council (SAMRC), Unit on Risk and Resilience in Mental Disorders, University of Cape Town, Cape Town, South Africa.

PMID: 40201449
PMCID: PMC11977823
DOI: 10.1162/nol_a_00161

Abstract

Prenatal alcohol exposure (PAE) is associated with various neurological, behavioral and cognitive deficits, including reading and language. Previous studies have demonstrated altered white matter in children and adolescents with PAE and associations with reading and language performance in children aged 3 years and older. However, little research has focused on the toddler years, despite this being a critical period for behavioral and neural development. We aimed to determine associations between structural brain connectivity and early language skills in toddlers, in the context of PAE. Eighty-eight toddlers (2-3 yr, 56 males), 23 of whom had PAE, underwent a diffusion MRI scan in Cape Town, South Africa, with language skills assessed using the Expressive and Receptive Communication subtests from the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III). Diffusion scans were preprocessed to create a structural network of regions associated with language skills using graph theory analysis. Linear regression models were used to examine moderation effects of PAE on structural network properties and language skills. Toddlers with PAE had higher structural connectivity in language networks than unexposed children. PAE moderated the relationship between structural network properties and Expressive Communication scores. None of the effects survived correction for multiple comparisons. Our findings show weak moderation effects of PAE on structural language network properties and language skills. Our study sheds light on the structural connectivity correlates of early language skills in an understudied population during a critical neurodevelopmental period, laying the foundation for future research.

Keywords: brain network; connectome; development; language; prenatal alcohol exposure.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

<b>Figure 1.</b> — **Figure 1.**
Left, bilateral, and right hemisphere language networks were defined as including the inferior temporal gyrus (light green; ITG), superior temporal gyrus (orange; STG), Heschl’s gyrus (yellow; HES), angular gyrus (navy blue; ANG), fusiform gyrus (sky blue; FFG), lingual gyrus (green; LING), triangular part of the inferior frontal gyrus (purple; IFG_T), and opercular part of the inferior frontal gyrus (red; IFG_O). Figure was generated using BrainNet Viewer (Xia et al., 2013).

<b>Figure 2.</b> — **Figure 2.**
Differences in graph theory metrics between prenatal alcohol exposure (PAE) and control (CON) groups. Clustering coefficient (top row), global efficiency (second row), local efficiency (third row), nodal degree (fourth row), and betweenness centrality (fifth row) in the bilateral network (16 × 16 matrix, first column), left network (8 × 8 matrix, second column), and right network (8 × 8 matrix, third column). The PAE group had higher clustering coefficient (p = 0.008) and local efficiency (p = 0.008) in the bilateral network compared to controls. ** indicates significant differences (p < 0.01); however, these differences did not survive multiple comparison correction (q < 0.05).

<b>Figure 3.</b> — **Figure 3.**
PAE moderated the Expressive Communication–graph theory metric associations for (A) global efficiency, (B) nodal degree, and (C) betweenness centrality in the right hemisphere network.

See this image and copyright information in PMC

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The Effects of Prenatal Alcohol Exposure on Structural Brain Connectivity and Early Language Skills in a South African Birth Cohort

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The Effects of Prenatal Alcohol Exposure on Structural Brain Connectivity and Early Language Skills in a South African Birth Cohort

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Abstract

Conflict of interest statement

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