Direct and Indirect Mechanisms of Alcohol Teratogenesis: Implications for Understanding Alterations in Brain and Behavior in FASD

Uban, Kristina A.; Bodnar, Tamara S.; Butts, Kelly A.; Śliwowska, Joanna H.; Comeau, Wendy; Weinberg, Joanne

doi:10.1002/9783527632510.ch5

Cited by 5 publications

(4 citation statements)

References 180 publications

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“…Similar HPA and brain alterations have been found to associate with PAE. Animal models of implicate HPA-dysregulation as a key mechanism of lasting harm of PAE on brain structural alterations in prefrontal and the limbic regions ( Uban et al, 2010 , 2013 ). Few studies to date have examined PAE, PTE, socioeconomic resources, and HPA-function and warrant future investigation.…”

Section: Discussionmentioning

confidence: 99%

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

Xia

Rebello

Bodison

et al. 2023

Front. Integr. Neurosci.

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BackgroundAlcohol 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.MethodsN = 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.ResultsGreater access to SER during pregnancy was associated with fewer ACEs (maternal education: β = −0.293,p = 0.01; phone access: β = −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 (β = 1.110,p = 0.01). SER was associated with alterations in superior frontal (β = −1336.036, q = 0.046), lateral orbitofrontal (β = −513.865, q = 0.046), caudal anterior cingulate volumes (β = −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 (β=1569.527, q = 0.013). PTE was associated with smaller volumes of lateral orbitofrontal (β = −331.000, q = 0.033) and nucleus accumbens regions (β = −34.800, q = 0.033).ConclusionResearch 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.

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Section: Discussionmentioning

confidence: 99%

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

Xia

Rebello

Bodison

et al. 2023

Front. Integr. Neurosci.

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“…Prenatal alcohol exposure (PAE) is one of the most common in-utero adverse substance exposures worldwide ( 1 ) and it is well documented that PAE has a significant negative impact on the developing brain ( 2 , 3 ). When PAE occurs at a sufficient frequency and/or volume, it can result in fetal alcohol spectrum disorder (FASD), which is a heterogenous neurodevelopmental disability affecting approximately 2%–5% of the North American population ( 4 ).…”

Section: Introductionmentioning

confidence: 99%

Factors predicting general health concerns and atypical behaviours in children with prenatal alcohol exposure and other adverse exposures

et al. 2023

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BackgroundPrenatal alcohol exposure (PAE) can have significant negative consequences on the health outcomes of children. Children with PAE often experience other prenatal and postnatal adverse exposures. Increased rates of general health concerns and atypical behaviours are seen in both children with PAE as well as with other patterns of adverse exposures, although these have not been systematically described. The association between multiple adverse exposures and adverse health concerns and atypical behaviours in children with PAE is unknown.MethodsDemographic information, medical history, adverse exposures, health concerns, and atypical behaviours were collected from children with confirmed PAE (n = 22; 14 males, age range = 7.9–15.9 years) and their caregivers. Support vector machine learning classification models were used to predict the presence of health concerns and atypical behaviours based on adverse exposures. Associations between the sums of adverse exposures, health concerns, and atypical behaviours were examined using correlation analysis.ResultsAll children experienced health concerns, the most common being sensitivity to sensory inputs (64%; 14/22). Similarly, all children engaged in atypical behaviours, with atypical sensory behaviour (50%; 11/22) being the most common. Prenatal alcohol exposure was most important factor for predicting some health concerns and atypical behaviours, and alone and in combination with other factors. Simple associations between adverse exposures could not be identified for many health concerns and atypical behaviours.ConclusionChildren with PAE and other adverse exposures experience high rates of health concerns and atypical behaviours. This study demonstrates the complex effects of multiple adverse exposures on health and behaviour in children.

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“…Prenatal alcohol exposure (PAE) is associated with brain abnormalities and neurocognitive difficulties (Uban et al, 2010). Fetal alcohol spectrum disorder (FASD) is the neurodevelopmental disorder related to heavy PAE (Cook et al, 2016), and its estimated prevalence ranges from 2% to 21% around the world (Lange et al, 2017; Popova et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Frontoparietal and temporal white matter diffusion MRI in children and youth with prenatal alcohol exposure

Gómez

Beaulieu

McMorris

et al. 2022

Alcoholism Clin & Exp Res

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Background: Prenatal alcohol exposure (PAE) is associated with brain alterations and neurocognitive deficits, but relationships between brain alterations and neurocognitive deficits remain unclear. Methods: Diffusion tensor imaging (DTI) data were obtained from 31 participants with PAE and 31 unexposed controls aged 7-15 years. Mean diffusivity (MD) and fractional anisotropy (FA) were derived from the genu, body, and splenium of the corpus callosum (CC), bilateral cingulum, and inferior and superior longitudinal fasciculus (ILF, SLF). Participants completed language subtests from the NEPSY-II. Executive functioning was measured using the Behavior Rating Inventory of Executive Functioning (BRIEF-PR) and verbal learning was assessed using the California Verbal Learning Test-Children's Version (CVLT-C) only in children with PAE. Group differences in diffusion metrics and cognitive scores were tested. Principal component analysis was used to reduce redundancy in cognitive and behavior variables; associations between components and brain measures were then assessed. Results: Children with PAE had lower MD in the right SLF compared with unexposed controls. FA was positively related to age in 6 of 9 tracts and MD negatively related to age in all tracts; there were no significant age-by-group interactions. Participants with PAE scored lower than unexposed peers on the NEPSY-II Comprehension of Instructions and Phonological Processing and above population norms (indicating worse performance) on the BRIEF-PR. Children with PAE had a negative association between a principal component closely associated with Speeded Naming and FA in the left SLF (PAE: p = 0.002) and left ILF (PAE: p = 0.002); unexposed controls showed no significant associations. Conclusion:We found widespread cognitive difficulties in children with PAE, but relatively limited differences in brain metrics and associations with age. Different brain-cognitive relationships were found in children with PAE compared with controls. Overall, the results provide additional evidence that PAE may lead to cognitive difficulties and disrupt typical brain-function relationships.

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Direct and Indirect Mechanisms of Alcohol Teratogenesis: Implications for Understanding Alterations in Brain and Behavior in FASD

Cited by 5 publications

References 180 publications

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

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

Factors predicting general health concerns and atypical behaviours in children with prenatal alcohol exposure and other adverse exposures

Frontoparietal and temporal white matter diffusion MRI in children and youth with prenatal alcohol exposure

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