Sex and age effects on gray matter volume trajectories in young children with prenatal alcohol exposure

Madison Long; Preeti Kar; Nils D Forkert; Bennett A Landman; W Ben Gibbard; Christina Tortorelli; Carly A McMorris; Yuankai Huo; Catherine A Lebel

doi:10.3389/fnhum.2024.1379959

Sex and age effects on gray matter volume trajectories in young children with prenatal alcohol exposure

Front Hum Neurosci. 2024 Apr 10:18:1379959. doi: 10.3389/fnhum.2024.1379959. eCollection 2024.

Authors

Madison Long^{1

2

3}, Preeti Kar^{1

2

3}, Nils D Forkert^{1

2

3}, Bennett A Landman^{4

5}, W Ben Gibbard^{2

6}, Christina Tortorelli⁷, Carly A McMorris^{2

3

6

8

9}, Yuankai Huo^{4

5}, Catherine A Lebel^{1

2

3}

Affiliations

¹ Department of Radiology, University of Calgary, Calgary, AB, Canada.
² Owerko Centre, Alberta Children Hospital Research Institute, University of Calgary, Calgary, AB, Canada.
³ Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.
⁴ Department of Electrical and Computer Engineering, Vanderbilt University, Nashville, TN, United States.
⁵ Department of Computer Science, Vanderbilt University, Nashville, TN, United States.
⁶ Department of Paediatrics, University of Calgary, Calgary, AB, Canada.
⁷ Department of Child Studies and Social Work, Mount Royal University, Calgary, AB, Canada.
⁸ Werklund School of Education, University of Calgary, Calgary, AB, Canada.
⁹ Mathison Centre for Mental Health Research and Education, Calgary, AB, Canada.

Abstract

Prenatal alcohol exposure (PAE) occurs in ~11% of North American pregnancies and is the most common known cause of neurodevelopmental disabilities such as fetal alcohol spectrum disorder (FASD; ~2-5% prevalence). PAE has been consistently associated with smaller gray matter volumes in children, adolescents, and adults. A small number of longitudinal studies show altered gray matter development trajectories in late childhood/early adolescence, but patterns in early childhood and potential sex differences have not been characterized in young children. Using longitudinal T1-weighted MRI, the present study characterized gray matter volume development in young children with PAE (N = 42, 84 scans, ages 3-8 years) compared to unexposed children (N = 127, 450 scans, ages 2-8.5 years). Overall, we observed altered global and regional gray matter development trajectories in the PAE group, wherein they had attenuated age-related increases and more volume decreases relative to unexposed children. Moreover, we found more pronounced sex differences in children with PAE; females with PAE having the smallest gray matter volumes and the least age-related changes of all groups. This pattern of altered development may indicate reduced brain plasticity and/or accelerated maturation and may underlie the cognitive/behavioral difficulties often experienced by children with PAE. In conjunction with previous research on older children, adolescents, and adults with PAE, our results suggest that gray matter volume differences associated with PAE vary by age and may become more apparent in older children.

Keywords: development; early childhood; gray matter volume; prenatal alcohol exposure; structural MRI; teratogen; trajectories.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. Data collection was supported by the Canadian Institutes of Health Research (grant numbers IHD134090, MOP-136797), and a grant from the Alberta Children’s Hospital Research Institute. This project was also supported by a scholarship from the Cummings School of Medicine at the University of Calgary.