Delayed cortical thinning in children and adolescents with prenatal alcohol exposure

Abstract

Background Prenatal alcohol exposure (PAE) is associated with abnormalities in cortical structure and maturation, including cortical thickness (CT), cortical volume, and surface area. This study provides a longitudinal context for the developmental trajectory and timing of abnormal cortical maturation in PAE. Methods We studied 35 children with PAE and 30 nonexposed typically developing children (Comparisons), aged 8–17 at enrollment, who were recruited from the University of Minnesota FASD Program. Participants were matched on age and sex. They underwent a formal evaluation of growth and dysmorphic facial features associated with PAE and completed cognitive testing. MRI data were collected on a Siemens Prisma 3T scanner. Two sessions, each including MRI scans and cognitive testing, were spaced approximately 15 months apart on average. Change in CT and performance on tests of executive function (EF) were examined. Results Significant age‐by‐group (PAE vs. Comparison) linear interaction effects in CT were observed in the parietal, temporal, occipital, and insular cortices suggesting altered developmental trajectories in the PAE vs. Comparison groups. Results suggest a pattern of delayed cortical thinning in PAE, with the Comparison group showing more rapid thinning at younger ages and those with PAE showing accelerated thinning at older ages. Overall, children in the PAE group showed reduced cortical thinning across time relative to the Comparison participants. Symmetrized percent change (SPC) in CT in several regions was significantly correlated with EF performance at 15‐month follow‐up for the Comparison group but not the group with PAE. Conclusions Regional differences were seen longitudinally in the trajectory and timing of CT change in children with PAE, suggesting delayed cortical maturation and an atypical pattern of development compared with typically developing individuals. In addition, exploratory correlation analyses of SPC and EF performance suggest the presence of atypical brain–behavior relationships in PAE. The findings highlight the potential role of altered developmental timing of cortical maturation in contributing to long‐term functional impairment in PAE.

Altered markers of brain metabolism and excitability are associated with executive functioning in young children exposed to alcoholin utero

“…Notably, our finding of higher tCho in PAE groups contrasts with prior evidence that showed lower tCho in older children and adolescents with PAE. This may point to altered developmental trajectories of phospholipid metabolism, myelination, and cortical development in PAE, consistent with findings from structural brain imaging studies (Gimbel et al, 2023; Kar et al, 2022). In fact, no differences in tCho were found in an MRS study of neonates with PAE (Howells et al, 2016), suggesting that alterations in tCho may emerge later in postnatal development and change over childhood.…”

“…These behavioral difficulties emerge in the context of PAE-related brain differences (Donald et al, 2015; Lebel et al, 2011; Moore & Xia, 2022). Reduced white matter and gray matter volume (Nardelli et al, 2011; Subramoney et al, 2022), altered microstructure and developmental trajectories (Donald et al, 2024; Gimbel et al, 2023; Kar et al, 2021, 2022; M. Long et al, 2024; X. Long & Lebel, 2022), and disrupted structural and functional connectivity (X.…”

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

“…Another area with large differences between male and female children with PAE was the right lingual gyrus, which was 16.6% larger in males. Previous research has indicated that the right lingual gyrus shows altered development of cortical structure, such as cortical thinning ( Gimbel et al, 2023 ) in individuals with PAE as compared to an unexposed group. While we are not aware of any other studies that have specifically examined sex effects on development of the right lingual gyrus, it may be that male and female children are differentially susceptible to the insult of PAE, manifesting in stark differences in gray matter regions that are prominently affected by PAE.…”

Association of in utero HIV exposure with child brain structure and language development: a South African birth cohort study

“…HEU children may therefore be demonstrating delayed cortical maturation or disrupted pruning or myelination at this early age. While the clinical significance of this remains to be determined, studies have found profiles of delayed cortical maturation may be associated with mood disorders [57], attention-deficit/ hyperactivity disorder [58], and autism spectrum disorders [59], as well as being linked to other exposures including alcohol [60,61] and infections such as cytomegalovirus infection (CMV) [62]. The process of cortical maturation is dynamic and there is substantial regional heterogeneity in the cortical thickness trajectory.…”