Prenatal alcohol exposure and white matter microstructural changes across the first 6-7 years of life: A longitudinal diffusion tensor imaging study of a South African birth cohort

K A Donald; C J Hendrikse; A Roos; C J Wedderburn; S Subramoney; J E Ringshaw; L Bradford; N Hoffman; T Burd; K L Narr; R P Woods; H J Zar; S H Joshi; D J Stein

doi:10.1016/j.nicl.2024.103572

Prenatal alcohol exposure and white matter microstructural changes across the first 6-7 years of life: A longitudinal diffusion tensor imaging study of a South African birth cohort

Neuroimage Clin. 2024:41:103572. doi: 10.1016/j.nicl.2024.103572. Epub 2024 Jan 28.

Authors

K A Donald¹, C J Hendrikse², A Roos³, C J Wedderburn⁴, S Subramoney², J E Ringshaw⁴, L Bradford², N Hoffman⁵, T Burd⁶, K L Narr⁷, R P Woods⁸, H J Zar⁶, S H Joshi⁹, D J Stein³

Affiliations

¹ Division of Developmental Paediatrics, Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa; Neuroscience Institute, University of Cape Town, Cape Town, South Africa. Electronic address: kirsty.donald@uct.ac.za.
² Division of Developmental Paediatrics, Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa.
³ Neuroscience Institute, University of Cape Town, Cape Town, South Africa; Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa; South African Medical Research Council (SAMRC), Unit on Risk and Resilience in Mental Disorders, University of Cape Town, Cape Town, South Africa.
⁴ Division of Developmental Paediatrics, Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa; Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
⁵ Neuroscience Institute, University of Cape Town, Cape Town, South Africa; Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa.
⁶ Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa; South African Medical Research Council (SAMRC), Unit on Child and Adolescent Health, University of Cape Town, Cape Town, South Africa.
⁷ Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, University of California Los Angeles, Los Angeles, CA, United States; Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA, United States.
⁸ Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, University of California Los Angeles, Los Angeles, CA, United States; Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA, United States; The Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA, United States; David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, United States.
⁹ Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, University of California Los Angeles, Los Angeles, CA, United States; Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, United States.

Abstract

Prenatal alcohol exposure (PAE) can affect brain development in early life, but few studies have investigated the effects of PAE on trajectories of white matter tract maturation in young children. Here we used diffusion weighted imaging (DWI) repeated over three time points, to measure the effects of PAE on patterns of white matter microstructural development during the pre-school years. Participants were drawn from the Drakenstein Child Health Study (DCHS), an ongoing birth cohort study conducted in a peri-urban community in the Western Cape, South Africa. A total of 342 scans acquired from 237 children as neonates (N = 82 scans: 30 PAE; 52 controls) and at ages 2-3 (N = 121 scans: 27 PAE; 94 controls) and 6-7 years (N = 139 scans: 45 PAE; 94 controls) were included. Maternal alcohol use during pregnancy and other antenatal covariates were collected from 28 to 32 weeks' gestation. Linear mixed effects models with restricted maxium likelihood to accommodate missing data were implemented to investigate the effects of PAE on fractional anisotropy (FA) and mean diffusivity (MD) in specific white matter tracts over time, while adjusting for child sex and maternal education. We found significant PAE-by-time effects on trajectories of FA development in the left superior cerebellar peduncle (SCP-L: p = 0.001; survived FDR correction) and right superior longitudinal fasciculus (SLF-R: p = 0.046), suggesting altered white matter development among children with PAE. Compared with controls, children with PAE demonstrated a more rapid change in FA in these tracts from the neonatal period to 2-3 years of age, followed by a more tapered trajectory for the period from 2-3 to 6-7 years of age, with these trajectories differing from unexposed control children. Given their supporting roles in various aspects of neurocognitive functioning (i.e., motor regulation, learning, memory, language), altered patterns of maturation in the SCP and SLF may contribute to a spectrum of physical, social, emotional, and cognitive difficulties often experienced by children with PAE. This study highlights the value of repeated early imaging in longitudinal studies of PAE, and focus for early childhood as a critical window of potential susceptibility as well as an opportunity for early intervention.

Keywords: Diffusion tensor imaging; Early brain development; Prenatal alcohol exposure; White matter maturation.

MeSH terms

Anisotropy
Birth Cohort
Brain / diagnostic imaging
Child
Child, Preschool
Cohort Studies
Diffusion Tensor Imaging / methods
Female
Humans
Infant, Newborn
Longitudinal Studies
Pregnancy
Prenatal Exposure Delayed Effects* / diagnostic imaging
South Africa
White Matter* / diagnostic imaging

Grants and funding

R01 AA026834/AA/NIAAA NIH HHS/United States