The impact of prenatal alcohol and/or tobacco exposure on brain structure in a large sample of children from a South African birth cohort

Abstract

Background Neuroimaging studies have emphasized the impact of prenatal alcohol exposure (PAE) on brain development, traditionally in heavily exposed participants. However, less is known about how naturally occurring community patterns of PAE (including light to moderate exposure) affect brain development, particularly in consideration of commonly occurring concurrent impacts of prenatal tobacco exposure (PTE). Methods Three hundred thirty‐two children (ages 8 to 12) living in South Africa's Cape Flats townships underwent structural magnetic resonance imaging. During pregnancy, their mothers reported alcohol and tobacco use, which was used to evaluate PAE and PTE effects on their children's brain structure. Analyses involved the main effects of PAE and PTE (and their interaction) and the effects of PAE and PTE quantity on cortical thickness, surface area, and volume. Results After false‐discovery rate (FDR) correction, PAE was associated with thinner left parahippocampal cortices, while PTE was associated with smaller cortical surface area in the bilateral pericalcarine, left lateral orbitofrontal, right posterior cingulate, right rostral anterior cingulate, left caudal middle frontal, and right caudal anterior cingulate gyri. There were no PAE × PTE interactions nor any associations of PAE and PTE exposure on volumetrics that survived FDR correction. Conclusion PAE was associated with reduction in the structure of the medial temporal lobe, a brain region critical for learning and memory. PTE had stronger and broader associations, including with regions associated with executive function, reward processing, and emotional regulation, potentially reflecting continued postnatal exposure to tobacco (i.e., second‐hand smoke exposure). These differential effects are discussed with respect to reduced PAE quantity in our exposed group versus prior studies within this geographical location, the deep poverty in which participants live, and the consequences of apartheid and racially and economically driven payment practices that contributed to heavy drinking in the region. Longer‐term follow‐up is needed to determine potential environmental and other moderators of the brain findings here and assess the extent to which they endure over time.

Contextualizing the impact of prenatal alcohol and tobacco exposure on neurodevelopment in a South African birth cohort: an analysis from the socioecological perspective

“…These functional correlates of lateral orbitofrontal cortex and nucleus accumbens are consistent with the negative association between PTE and global cognition in children between 9 to 12 years old found in the current literature, suggesting a potential brain-behavior relationship ( Fried et al, 1998 ; Gonzalez et al, 2023 ). Our results are consistent with prior studies from this same birth cohort representing community patterns of PAE and PTE, showing more widespread cortical and subcortical brain alterations with PTE compared to PAE at ages 6 years old ( Uban et al, 2023 ) and ages 8–12 years ( Marshall et al, 2022 ). Compared to alcohol, tobacco use is less likely to be cut back during pregnancy and more likely to be associated with tobacco exposure after pregnancy ( Leech et al, 1999 ; Cornelius and Day, 2000 ).…”

“…The potential for PTE from others’ use may be a mechanism for reaching higher doses of exposure, and/or longer durations of exposure across postnatal developmental stages, unlike PAE. Together, these mechanisms for PTE that are unique from those of PAE may explain the more widespread effects on brain development at ages 6 ( Uban et al, 2023 ) and 8–11 years as seen here and in Marshall et al (2022) . Interestingly, PTE dose-response relationships did not show significant results after corrections for multiple comparisons ( Marshall et al, 2022 ), suggesting that PTE exposure from the postnatal period, or relating to perinatal tobacco exposure from others around the pregnant person or baby may be driving PTE outcomes more than maternal use in pregnancy alone.…”

Brain structural differences in children with fetal alcohol spectrum disorder and its subtypes

“…Magnetic resonance imaging (MRI) studies of individuals with PAE have identified structural changes in brain size and shape (including microcephaly), gray and white matter volumes, cortical thickness (CT), and surface area (SA) in children, adolescents, and young adults ( Sowell et al, 2002b ; Riley et al, 2004 ; Lebel et al, 2011 ; Zhou et al, 2011 ; Roussotte et al, 2012 ; Yang et al, 2012a ). While the severity of abnormalities is positively correlated with higher doses of PAE ( Sowell et al, 2008 ; Zhou et al, 2011 ; Hoyme et al, 2016 ; Marshall et al, 2022 ), some studies found teratogenic effects due to PAE even in cases of minimal alcohol consumption in humans ( Joseph et al, 2014 ; Williams and Smith, 2015 ; Marshall et al, 2022 ).…”

Longitudinal effects of prenatal alcohol exposure on visual neurodevelopment over infancy.

“…It is important to recognize the structural and cultural factors, including historical sociopolitical frameworks, which might contribute to the high prevalence of PAE present in certain South African communities. The colonial apartheid regime in South Africa created a system of significant economic and sociopolitical inequalities that served to disadvantage communities such as those in the current study sample (Adebiyi et al, 2021; Jacobson et al, 2017; Marshall et al, 2022; May et al, 2019). Additionally, in health systems with access to limited resources, more acutely life-threatening medical conditions may be prioritized over conditions that are more chronic and less immediately life-threatening, leading to less resource allocation to mental health and substance use disorder treatment and support (Williams & Wyatt, 2015).…”