Prenatal tobacco and alcohol exposure, white matter microstructure, and early language skills in toddlers from a South African birth cohort

Chloe Scholten; Mohammad Ghasoub; Bryce Geeraert; Shantanu Joshi; Catherine J Wedderburn; Annerine Roos; Sivenesi Subramoney; Nadia Hoffman; Katherine Narr; Roger Woods; Heather J Zar; Dan J Stein; Kirsten Donald; Catherine Lebel

doi:10.3389/fnint.2024.1438888

Prenatal tobacco and alcohol exposure, white matter microstructure, and early language skills in toddlers from a South African birth cohort

Front Integr Neurosci. 2024 Sep 2:18:1438888. doi: 10.3389/fnint.2024.1438888. eCollection 2024.

Authors

Chloe Scholten^{1

2}, Mohammad Ghasoub^{1

2}, Bryce Geeraert^{1

2}, Shantanu Joshi^{3

4}, Catherine J Wedderburn^{5

6}, Annerine Roos^{6

7

8}, Sivenesi Subramoney⁵, Nadia Hoffman⁷, Katherine Narr^{3

9}, Roger Woods^{3

9

10

11}, Heather J Zar^{12

13}, Dan J Stein^{6

7

8}, Kirsten Donald^{5

6}, Catherine Lebel^{1

2

14}

Affiliations

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

Abstract

Introduction: Tobacco and alcohol are the two most common substances used during pregnancy, and both can disrupt neurodevelopment, resulting in cognitive and behavioral deficits including language difficulties. Previous studies show that children with prenatal substance exposure exhibit microstructural alterations in major white matter pathways, though few studies have investigated the impact of prenatal substance exposure on white matter microstructure and language skills during the toddler years.

Methods: In this study, 93 children (34 exposed to alcohol and/or tobacco) aged 23 years from the Drakenstein Child Health Study, South Africa, completed Expressive and Receptive Communication assessments from the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) and underwent diffusion MRI scans. Diffusion images were preprocessed, and 11 major white matter tracts were isolated. Fractional anisotropy (FA) and mean diffusivity (MD) were extracted for each white matter tract. Linear regression was used to examine differences between the tobacco/alcohol exposed group and unexposed controls for FA, MD, and language scores, as well as relationships between brain metrics and language. There were no significant group differences in language scores or FA.

Results: Children with alcohol or tobacco exposure had lower average MD in the splenium of the corpus callosum compared to unexposed controls. Significant interactions between prenatal substance exposure and language scores were seen in 7 tracts but did not survive multiple comparisons correction.

Discussion: Our findings show that prenatal alcohol and/or tobacco exposure appear to alter the relationship between white matter microstructure and early language skills in this population of toddlers, potentially laying the basis of language deficits observed later in older children with prenatal substance exposure, which may have implications for learning and interventions.

Keywords: development; diffusion tensor imaging (DTI); early language; prenatal alcohol exposure (PAE); prenatal tobacco exposure.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was funded by the Jacobs Foundation, and Bill and Melinda Gates Foundation (OPP 1017641) and this particular sub-study was supported through a US Brain and Behavior Foundation Independent Investigator grant (24467) awarded to KD. KD and additional aspects of the research were supported by the SA National Research Foundation (NRF), an Academy of Medical Sciences Newton Advanced Fellowship (NAF002/1001) funded by the UK Government's Newton Fund, by NIAAA via (R21AA023887 and R01 AA026834-01), by the Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CIFASD) developmental grant (U24 AA014811). Additional support for HZ and DS was provided by the Medical Research Council of South Africa. CW was supported by the Wellcome Trust through a Research Training Fellowship [203525/Z/16/Z]. AR was supported by the SA NRF. MG was supported by the Hotchkiss Brain Institute. CL receives salary support from the Canada Research Chairs Program.