Prenatal alcohol exposure is associated with altered cortical structure and neurocognition at age 6
Poster No:
390
Submission Type:
Abstract Submission
Authors:
Chanelle Hendrikse1, Shantanu Joshi2, Jessica Ringshaw1, Layla Bradford1, Annerine Roos1, Catherine Wedderburn1, Nadia Hoffman1, Tiffany Burd1, Katherine Narr2, Roger Woods2, Heather Zar1, Dan Stein1, Kirsty Donald1
Institutions:
1University of Cape Town, Cape Town, South Africa, 2University of California Los Angeles, Los Angeles, CA
First Author:
Co-Author(s):
Introduction:
We previously reported widespread brain structural changes in 2-3-year-old children with prenatal alcohol exposure (PAE; Subramoney et al., 2022) in a South African birth cohort study, the Drakenstein Child Health Study (DCHS), which may underpin foetal alcohol spectrum disorders symptomatology. However, few studies have examined the associations between PAE-related brain structural changes and neurocognitive functions through middle childhood. We aimed to examine the potential associations between PAE and cortical and subcortical grey matter morphology and neurocognitive outcomes in 6-7-year-old children.
Methods:
One hundred fifty-eight children (49 PAE, 109 controls; 46% female; mean age 76 ± 5 months) participating in a brain imaging substudy of the DCHS in Cape Town, South Africa, were included (Donald et al., 2018; Zar et al., 2015). Maternal alcohol use during pregnancy was prospectively assessed using the Alcohol, Smoking, and Substance Involvement Screening Test, with additional data on quantity and timing reported soon after birth. Using a 3T MRI scanner, high-resolution T1-weighted brain structural scans were acquired on children at 6-7 years and processed using FreeSurfer 7.1.1. In SPSS, general linear models (GLMs) were used to test the associations between PAE (categorical variable) and global and regional cortical metrics (i.e., volume [CV], surface area [CSA], thickness [CT]) and subcortical volumes. Cortical regions of interest (ROIs) spanning the frontal, parietal, temporal, and occipital lobes were assessed in a lobe-wise manner. The Benjamini-Hochberg false discovery rate (FDR) method was applied to correct for multiple comparisons. Covariates were child age, sex, maternal education, prenatal tobacco exposure, and¬-in volumetric models only-total intracranial volume. Associations between PAE and neurocognitive outcomes, as assessed using the Early Learning Outcomes Measure (ELOM; n = 119) specifically designed for South African children, were examined. The potential mediating influence of significant PAE-related brain structural effects on associations between PAE and neurocognitive outcomes was assessed using the PROCESS macro for SPSS (Hayes, 2022) while adjusting for the same covariates.
Results:
PAE was associated with lower total CSA (p = 0.044), as well as regional CV and CSA reductions in frontal, parietal, and temporal lobe ROIs, and CT increases in specific parietal and occipital lobe ROIs. PAE effects on CSA in the right superior parietal and precuneus cortices survived FDR correction. A main multivariate PAE effect on regional CSA of temporal ROIs was found which survived FDR correction, eliminating the need for further FDR corrections in post hoc univariate GLMs with individual ROIs in this lobe-PAE was associated with lower CSA in the left middle temporal and right inferior temporal, fusiform and parahippocampal gyri (Figure 1). Moreover, PAE was associated with poorer ELOM total (p = 0.002) and subscale scores for the numeracy/mathematics (p < 0.001), cognition/executive functioning (p = 0.029), and language/literacy subscales (p = 0.012). CSA of the left middle temporal gyrus partially mediated the associations between PAE and ELOM total scale scores, as well as the numeracy/mathematics and cognition/executive functioning subscale scores (Figure 2).
Conclusions:
We found widespread PAE effects on cortical morphology at 6-7 years, expanding our earlier findings at 2-3 years (Subramoney et al., 2022). While frontal and occipital effects were present, CSA of parietal and temporal ROIs appeared to be most affected by PAE. Smaller CSA suggests immature gyrification in these regions involved in numerous cognitive and sensorimotor functions. Increased efforts to reduce maternal drinking during pregnancy and early interventions for children with PAE are needed to enhance school readiness.
Disorders of the Nervous System:
Neurodevelopmental/ Early Life (eg. ADHD, autism) 1
Modeling and Analysis Methods:
Segmentation and Parcellation 2
Keywords:
Cognition
Cortex
Development
Learning
Morphometrics
PEDIATRIC
STRUCTURAL MRI
Other - prenatal alcohol exposure
1|2Indicates the priority used for review
Provide references using author date format
Subramoney, S., Joshi, S. H., Wedderburn, C. J., Lee, D., Roos, A., Woods, R. P., Zar, H. J., Narr, K. L., Stein, D. J., & Donald, K. A. (2022). The impact of prenatal alcohol exposure on gray matter volume and cortical surface area of 2 to 3-year-old children in a South African birth cohort. Alcoholism, clinical and experimental research, 46(7), 1233–1247. https://doi.org/10.1111/acer.14873
Hayes, A. F. (2022). Introduction to mediation, moderation, and conditional process analysis: A regression-based approach (3rd edition), Guilford Press, New York, NY.
Zar, H. J., Barnett, W., Myer, L., Stein, D. J., & Nicol, M. P. (2015). Investigating the early-life determinants of illness in Africa: the Drakenstein Child Health Study. Thorax, 70(6), 592–594. https://doi.org/10.1136/thoraxjnl-2014-206242