Associations between community-level patterns of prenatal alcohol and tobacco exposure on brain structure in a non-clinical sample of 6-year-old children: a South African pilot study.

The current small study utilised prospective data collection of patterns of prenatal alcohol and tobacco exposure (PAE and PTE) to examine associations with structural brain outcomes in 6-year-olds and served as a pilot to determine the value of prospective data describing community-level patterns of PAE and PTE in a non-clinical sample of children. Participants from the Safe Passage Study in pregnancy were approached when their child was ∼6 years old and completed structural brain magnetic resonance imaging to examine with archived PAE and PTE data (n = 51 children-mother dyads). Linear regression was used to conduct whole-brain structural analyses, with false-discovery rate (FDR) correction, to examine: (a) main effects of PAE, PTE and their interaction; and (b) predictive potential of data that reflect patterns of PAE and PTE (e.g. quantity, frequency and timing (QFT)). Associations between PAE, PTE and their interaction with brain structural measures demonstrated unique profiles of cortical and subcortical alterations that were distinct between PAE only, PTE only and their interactive effects. Analyses examining associations between patterns of PAE and PTE (e.g. QFT) were able to significantly detect brain alterations (that survived FDR correction) in this small non-clinical sample of children. These findings support the hypothesis that considering QFT and co-exposures is important for identifying brain alterations following PAE and/or PTE in a small group of young children. Current results demonstrate that teratogenic outcomes on brain structure differ as a function PAE, PTE or their co-exposures, as well as the pattern (QFT) or exposure.

Sex-specific impulsivity, but not other facets of executive function, predicts fat and sugar intake two-years later amongst adolescents with a healthy weight: Findings from the ABCD study.

During adolescence, processes that control food intake (executive functions [EF]) undergo extensive refinement; underlying differences in EF may explain the inability to resist overeating unhealthy foods. Yet, overeating fat and sugar also causes changes to EF and cognition but disentangling these relationships has been difficult, as previous studies included youth with obesity. Here, amongst youth initially of a healthy weight, we evaluate whether 1) sex-specific underlying variation in EF/cognition at 9/10-years-old predict fat/sugar two-years later (Y2) and 2) if these relationships are moderated by body mass index (BMI), using linear mixed effects models (controlled for puberty, caregiver education; random effect: study site). Data were leveraged from Adolescent Brain Cognitive Development Study (n = 2987; 50.4% male; 15.4% Latino/a/x; 100% healthy weight at baseline; 12.4% overweight/obese by Y2, data release 4.0). EF and cognition (e.g., inhibition, cognition, motor, memory, impulsivity) were assessed with the NIH toolbox, Rey Auditory Verbal Learning Task, Little Man Task, the BIS/BAS, and UPPS-P. A saturated fat/added sugar (kcals) composite score was extracted from the validated Kids Food Block Screener. For males, greater baseline impulsivity (e.g., Positive Urgency, Lack of Planning and Perseverance) and reward (e.g., Fun seeking, Drive) was related to greater Y2 intake. For both sexes, greater baseline Negative Urgency and higher BMI was related to greater Y2 intake. No other relationships were observed. Our findings highlight a phenotype that may be more at risk for weight gain due to overconsumption of fat/sugar. Thus, prevention efforts may wish to focus on impulsive tendencies for these foods.

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

Background: Alcohol and tobacco are known teratogens. Historically, more severe prenatal alcohol exposure (PAE) and prenatal tobacco exposure (PTE) have been examined as the principal predictor of neurodevelopmental alterations, with little incorporation of lower doses or ecological contextual factors that can also impact neurodevelopment, such as socioeconomic resources (SER) or adverse childhood experiences (ACEs). Here, a novel analytical approach informed by a socio-ecological perspective was used to examine the associations between SER, PAE and/or PTE, and ACEs, and their effects on neurodevelopment. Methods: N = 313 mother-child dyads were recruited from a prospective birth cohort with maternal report of PAE and PTE, and cross-sectional structural brain neuroimaging of child acquired via 3T scanner at ages 8-11 years. In utero SER was measured by maternal education, household income, and home utility availability. The child's ACEs were measured by self-report assisted by the researcher. PAE was grouped into early exposure (<12 weeks), continued exposure (>=12 weeks), and no exposure controls. PTE was grouped into exposed and non-exposed controls. Results: Greater access to SER during pregnancy was associated with fewer ACEs (maternal education: ß = -0.293,p = 0.01; phone access: ß = -0.968,p = 0.05). PTE partially mediated the association between SER and ACEs, where greater SER reduced the likelihood of PTE, which was positively associated with ACEs (ß = 1.110,p = 0.01). SER was associated with alterations in superior frontal (ß = -1336.036, q = 0.046), lateral orbitofrontal (ß = -513.865, q = 0.046), caudal anterior cingulate volumes (ß = -222.982, q = 0.046), with access to phone negatively associated with all three brain volumes. Access to water was positively associated with superior frontal volume (ß=1569.527, q = 0.013). PTE was associated with smaller volumes of lateral orbitofrontal (ß = -331.000, q = 0.033) and nucleus accumbens regions (ß = -34.800, q = 0.033). Conclusion: Research on neurodevelopment following community-levels of PAE and PTE should more regularly consider the ecological context to accelerate understanding of teratogenic outcomes. Further research is needed to replicate this novel conceptual approach with varying PAE and PTE patterns, to disentangle the interplay between dose, community-level and individual-level risk factors on neurodevelopment.

Prenatal tobacco exposure associations with physical health and neurodevelopment in the ABCD cohort.

OBJECTIVE: To investigate the strength and reproducibility of the teratogenic impact of prenatal tobacco exposure (PTE) on child physical health and neurodevelopmental outcomes, in the context of intersecting sociodemographic and other prenatal correlates, and test if early postnatal health mediates PTE associations with childhood outcomes. METHOD: Among 9-10-year-olds (N = 8,803) in the Adolescent Brain Cognitive Development Study, linear mixed-effect models tested PTE associations with birth and childhood outcomes of physical health, cognitive performance, and brain structure, controlling for confounding sociodemographic and prenatal health correlates. Mediation analysis tested the extent to which health at birth explained the associations between PTE and childhood outcomes. RESULTS: PTE was reported by 12% of mothers (8% [n = 738] pre-knowledge of pregnancy only, and 4% [n = 361] pre- and post-knowledge of pregnancy). PTE was highest for children with a risk for passive smoke exposure. Overall, children with any PTE had shorter breastfeeding durations than those without PTE, and PTE following knowledge of pregnancy was associated with being small for gestational age having lower birth weight, and obesity and lower cortical volume and surface area in childhood. Among children from high-parent education households, any PTE was related to lower cognitive performance, which was partially mediated by duration of breastfeeding. CONCLUSIONS: PTE was linked to poorer health indicators at birth and neurodevelopmental outcomes at age 9-10 years in a large community cohort, independent of sociodemographic factors. Efficacious interventions for smoking-cessation during pregnancy are still needed and should incorporate support for breastfeeding to promote healthier development. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Relating neighborhood deprivation to childhood obesity in the ABCD study: Evidence for theories of neuroinflammation and neuronal stress.

OBJECTIVE: We evaluated whether relationships between area deprivation (ADI), body mass index (BMI) and brain structure (e.g., cortical thickness, subcortical volume) during preadolescence supported the immunologic model of self-regulation failure (NI) and/or neuronal stress (NS) theories of overeating. The NI theory proposes that ADI causes structural alteration in the brain due to the neuroinflammatory effects of overeating unhealthy foods. The NS theory proposes that ADI-related stress negatively impacts brain structure, which causes stress-related overeating and subsequent obesity. METHOD: Data were gathered from the Adolescent Brain Cognitive Development Study (9 to 12 years old; n = 3,087, 51% male). Linear mixed-effects models identified brain regions that were associated with both ADI and BMI; longitudinal associations were evaluated with mediation models. The NI model included ADI and BMI at 9 to 10 years old and brain data at 11 to 12 years old. The NS model included ADI and brain data at 9 to 10 years old and BMI at 11 to 12 years old. RESULTS: BMI at 9 to 10 years old partially mediated the relationship between ADI and ventral diencephalon (DC) volume at 11 to 12 years old. Additionally, the ventral DC at 9 to 10 years old partially mediated the relationship between ADI and BMI at 11 to 12 years old, even in youth who at baseline, were of a healthy weight. Results were unchanged when controlling for differences in brain structure and weight across the 2-years. CONCLUSION: Greater area deprivation may indicate fewer access to resources that support healthy development, like nutritious food and nonstressful environments. Our findings provide evidence in support of the NI and NS theories of overeating, specifically, with greater ADI influencing health outcomes of obesity via brain structure alterations. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

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

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.

Neural correlates of verbal memory in youth with heavy prenatal alcohol exposure.

Prenatal alcohol exposure can impact both brain development and neurobehavioral function, including verbal learning and recall, although the relation between verbal recall and brain structure in this population has not been examined fully. We aimed to determine the structural neural correlates of verbal learning and recall in youth with histories of heavy prenatal alcohol exposure using a region of interest (ROI) approach. As part of an ongoing multisite project, subjects (age 10-16 years) with prenatal alcohol exposure (AE, n = 81) and controls (CON, n = 81) were tested using the CVLT-C and measures of cortical volume, surface area, and thickness as well as hippocampal volume were derived from MRI. Group differences in brain and memory indices were tested with ANOVA. Multiple regression analyses tested whether brain ROIs significantly predicted memory performance. The AE group had lower scores than the CON group on all CVLT-C variables (ps ≤ .001) and volume and surface area (ps < .025), although results varied by ROI. No group differences in cortical thickness were found. The relations between cortical structure and memory performance differed between group among some ROIs, particularly those in the frontal cortex, generally with smaller surface area and/or thinner cortex predicting better performance in CON but worse performance in AE. Cortical surface area appears to be the most sensitive index to the effects of prenatal alcohol exposure, while cortical thickness appears to be the least sensitive. These findings also indicate that the neural correlates of verbal memory are altered in youth with heavy prenatal alcohol exposure compared to controls.

Executive function and cortical thickness in youths prenatally exposed to cocaine, alcohol and tobacco.

Small and detrimental, albeit inconsistent, effects of prenatal cocaine exposure (PCE) during early childhood have been reported. The teratogenic effects of prenatal alcohol (PAE) and tobacco exposure (PTE) on neurobehavior are more firmly established than PCE. We tested if co-exposure to all three drugs could be related to greater differences in brain structure than exposure to cocaine alone. Participants (n=42, PCE=27; age range=14-16 years) received an executive function battery prior to a T1-weighted 3T structural MRI scan. Cortical thickness was measured using FreeSurfer (v5.1). Fetal drug exposure was quantified through maternal self-reports usage during pregnancy. Using general linear modeling, we found no main effects of PCE on cortical thickness, but significant main effects of PAE and PTE in superior and medial frontal regions, after co-varying for the effects of age, sex, and each drug of exposure. Significant alcohol-by-tobacco interactions, and significant cocaine-by-alcohol interactions on cortical thickness in medial parietal and temporal regions were also observed. Poly-drug exposure and cognitive function also showed significant interactions with cortical thickness: lower cortical thickness was associated with better performance in PCE-exposed adolescents. Results suggest that although children with PCE have subtle but persistent brain cortical differences until mid-to-late adolescence.

A longitudinal study: changes in cortical thickness and surface area during pubertal maturation.

Sex hormones have been shown to contribute to the organization and function of the brain during puberty and adolescence. Moreover, it has been suggested that distinct hormone changes in girls versus boys may contribute to the emergence of sex differences in internalizing and externalizing behavior during adolescence. In the current longitudinal study, the influence of within-subject changes in puberty (physical and hormonal) on cortical thickness and surface area was examined across a 2-year span, while controlling for age. Greater increases in Tanner Stage predicted less superior frontal thinning and decreases in precuneus surface area in both sexes. Significant Tanner Stage and sex interactions were also seen, with less right superior temporal thinning in girls but not boys, as well as greater decreases in the right bank of the superior temporal sulcus surface area in boys compared to girls. In addition, within-subject changes in testosterone over the 2-year follow-up period were found to relate to decreases in middle superior frontal surface area in boys, but increases in surface area in girls. Lastly, larger increases in estradiol in girls predicted greater middle temporal lobe thinning. These results show that within-subject physical and hormonal markers of puberty relate to region and sex-specific changes in cortical development across adolescence.

The role of testosterone and estradiol in brain volume changes across adolescence: a longitudinal structural MRI study.

It has been postulated that pubertal hormones may drive some neuroanatomical changes during adolescence, and may do so differently in girls and boys. Here, we use growth curve modeling to directly assess how sex hormones [testosterone (T) and estradiol (E2)] relate to changes in subcortical brain volumes utilizing a longitudinal design. 126 adolescents (63 girls), ages 10 to 14, were imaged and restudied ∼2 years later. We show, for the first time, that best-fit growth models are distinctly different when using hormones as compared to a physical proxy of pubertal maturation (Tanner Stage) or age, to predict brain development. Like Tanner Stage, T and E2 predicted white matter and right amygdala growth across adolescence in both sexes, independent of age. Tanner Stage also explained decreases in both gray matter and caudate volumes, whereas E2 explained only gray matter decreases and T explained only caudate volume decreases. No pubertal measures were related to hippocampus development. Although specificity was seen, sex hormones had strikingly similar relationships with white matter, gray matter, right amygdala, and bilateral caudate volumes, with larger changes in brain volume seen at early pubertal maturation (as indexed by lower hormone levels), followed by less robust, or even reversals in growth, by late puberty. These novel longitudinal findings on the relationship between hormones and brain volume change represent crucial first steps toward understanding which aspects of puberty influence neurodevelopment.