Effects of prenatal alcohol exposure on the development of white matter volume and change in executive function

Prenatal alcohol exposure (PAE) can lead to cognitive, behavioural, and social-emotional challenges. Previous neuroimaging research has identified alterations to brain structure in newborns, older children, adolescents, and adults with PAE; however, little is known about brain structure in young children. Extensive brain development takes place during early childhood; therefore, understanding the neurological profiles of young children with PAE is critical for early identification and effective intervention. We studied 54 children (5.21 +/- 1.11 years; 27 males) with confirmed PAE compared to 54 age- and sex-matched children without PAE. Children underwent diffusion tensor imaging between 2 and 7 years of age. Mean fractional anisotropy (FA) and mean diffusivity (MD) were obtained for 10 major white matter tracts, along with tract volume, axial and radial diffusivity (AD, RD). A univariate analysis of covariance was conducted to test for group differences (PAE vs. control) controlling for age, sex and tract volume. Our results reveal white matter microstructural differences between young children with PAE and unexposed controls. The PAE group had higher FA and/or lower MD (as well as lower AD and RD) in the genu and the body of the corpus callosum, as well as the bilateral uncinate fasciculus and pyramidal tracts. Our findings align with studies of newborns with PAE finding lower AD, but contrast those in older populations with PAE, which consistently report lower FA and higher MD. These findings may reflect premature development of white matter that may then plateau too early, leading to the lower FA/higher MD observed at older ages.

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Executive Functioning Correlates With Communication Ability in Youth With Histories of Heavy Prenatal Alcohol Exposure

Journal of the International Neuropsychological Society ◽

10.1017/s1355617718000772 ◽

2018 ◽

Vol 24 (10) ◽

pp. 1026-1037 ◽

Cited By ~ 4

Author(s):

Lauren R. Doyle ◽

Eileen M. Moore ◽

Claire D. Coles ◽

Julie A. Kable ◽

Elizabeth R. Sowell ◽

...

Keyword(s):

Working Memory ◽

Executive Function ◽

Fetal Alcohol Spectrum Disorders ◽

Spatial Working Memory ◽

Prenatal Alcohol Exposure ◽

Alcohol Exposure ◽

Global Model ◽

Vineland Adaptive Behavior Scales ◽

Communication Ability ◽

Prenatal Alcohol

AbstractObjectives: Caregivers of youth with heavy prenatal alcohol exposure report impaired communication, which can significantly impact quality of life. Using data collected as part of the Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CIFASD), we examined whether cognitive variables predict communication ability of youth with histories of heavy prenatal alcohol exposure. Methods: Subjects (ages 10–16 years) comprised two groups: adolescents with heavy prenatal alcohol exposure (AE) and non-exposed controls (CON). Selected measures of executive function (NEPSY, Delis-Kaplan Executive Function System), working memory (CANTAB), and language were tested in the child, while parents completed communication ratings (Vineland Adaptive Behavior Scales – Second Edition). Separate multiple regression analyses determined which cognitive domains predicted communication ability. A final, global model of communication comprised the three cognitive models. Results: Spatial Working Memory and Inhibition significantly contributed to communication ability across groups. Twenty Questions performance related to communication ability in the CON group only while Word Generation performance related to communication ability in the AE group only. Effects remained significant in the global model, with the exception of Spatial Working Memory. Conclusions: Both groups displayed a relation between communication and Spatial Working Memory and Inhibition. Stronger communication ability related to stronger verbal fluency in the AE group and Twenty Questions performance in the CON group. These findings suggest that alcohol-exposed adolescents may rely more heavily on learned verbal storage or fluency for daily communication while non-exposed adolescents may rely more heavily on abstract thinking and verbal efficiency. Interventions aimed at aspects of executive function may be most effective at improving communication ability of these individuals. (JINS, 2018, 24, 1026–1037)

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White matter integrity of the cerebellar peduncles as a mediator of effects of prenatal alcohol exposure on eyeblink conditioning

Human Brain Mapping ◽

10.1002/hbm.22785 ◽

2015 ◽

Vol 36 (7) ◽

pp. 2470-2482 ◽

Cited By ~ 15

Author(s):

Jia Fan ◽

Ernesta M. Meintjes ◽

Christopher D. Molteno ◽

Bruce S. Spottiswoode ◽

Neil C. Dodge ◽

...

Keyword(s):

White Matter ◽

Eyeblink Conditioning ◽

Prenatal Alcohol Exposure ◽

Alcohol Exposure ◽

White Matter Integrity ◽

Cerebellar Peduncles ◽

Prenatal Alcohol

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White matter abnormalities in fetal alcohol spectrum disorders: Focus on axon growth and guidance

Experimental Biology and Medicine ◽

10.1177/1535370220980398 ◽

2021 ◽

pp. 153537022098039

Author(s):

Erin Mathews ◽

Kevyn Dewees ◽

Deborah Diaz ◽

Carlita Favero

Keyword(s):

White Matter ◽

Fetal Alcohol Spectrum Disorders ◽

Prenatal Alcohol Exposure ◽

Alcohol Exposure ◽

Fetal Alcohol ◽

White Matter Abnormalities ◽

Guidance Cue ◽

Prenatal Alcohol ◽

Spectrum Disorders ◽

Fetal Alcohol Spectrum

Fetal Alcohol Spectrum Disorders (FASDs) describe a range of deficits, affecting physical, mental, cognitive, and behavioral function, arising from prenatal alcohol exposure. FASD causes widespread white matter abnormalities, with significant alterations of tracts in the cerebral cortex, cerebellum, and hippocampus. These brain regions present with white-matter volume reductions, particularly at the midline. Neural pathways herein are guided primarily by three guidance cue families: Semaphorin/Neuropilin, Netrin/DCC, and Slit/Robo. These guidance cue/receptor pairs attract and repulse axons and ensure that they reach the proper target to make functional connections. In several cases, these signals cooperate with each other and/or additional molecular partners. Effects of alcohol on guidance cue mechanisms and their associated effectors include inhibition of growth cone response to repellant cues as well as changes in gene expression. Relevant to the corpus callosum, specifically, developmental alcohol exposure alters GABAergic and glutamatergic cell populations and glial cells that serve as guidepost cells for callosal axons. In many cases, deficits seen in FASD mirror aberrancies in guidance cue/receptor signaling. We present evidence for the need for further study on how prenatal alcohol exposure affects the formation of neural connections which may underlie disrupted functional connectivity in FASD.

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Validity and Reliability of Executive Function Measures in Children With Heavy Prenatal Alcohol Exposure: Correspondence Between Multiple Raters and Laboratory Measures

Alcoholism Clinical and Experimental Research ◽

10.1111/acer.14547 ◽

2021 ◽

Author(s):

Gemma A. Bernes ◽

Miguel Villodas ◽

Claire D. Coles ◽

Julie A. Kable ◽

Philip A. May ◽

...

Keyword(s):

Executive Function ◽

Prenatal Alcohol Exposure ◽

Alcohol Exposure ◽

Validity And Reliability ◽

Prenatal Alcohol ◽

Laboratory Measures

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The Clinical Utility and Specificity of Parent Report of Executive Function among Children with Prenatal Alcohol Exposure

Journal of the International Neuropsychological Society ◽

10.1017/s1355617714000599 ◽

2014 ◽

Vol 20 (7) ◽

pp. 704-716 ◽

Cited By ~ 22

Author(s):

Tanya T. Nguyen ◽

Leila Glass ◽

Claire D. Coles ◽

Julie A. Kable ◽

Philip A. May ◽

...

Keyword(s):

Executive Function ◽

Function Analysis ◽

Prenatal Alcohol Exposure ◽

Alcohol Exposure ◽

Parent Report ◽

Parent Ratings ◽

Behavioral Issues ◽

Neuropsychological Measures ◽

Prenatal Alcohol ◽

Main Effects

AbstractPrenatal alcohol exposure and attention-deficit/hyperactivity disorder (ADHD) result in behavioral issues related to poor executive function (EF). This overlap may hinder clinical identification of alcohol-exposed children. This study examined the relation between parent and neuropsychological measures of EF and whether parent ratings aid in differential diagnosis. Neuropsychological measures of EF, including the Delis-Kaplan Executive Function System (D-KEFS), were administered to four groups of children (8–16 years): alcohol-exposed with ADHD (AE+, n=80), alcohol-exposed without ADHD (AE−, n=36), non-exposed with ADHD (ADHD, n=93), and controls (CON, n=167). Primary caregivers completed the Behavior Rating Inventory of Executive Function (BRIEF). For parent ratings, multivariate analyses of variance revealed main effects of Exposure and ADHD and an interaction between these factors, with significant differences between all groups on nearly all BRIEF scales. For neuropsychological measures, results indicated main effects of Exposure and ADHD, but no interaction. Discriminant function analysis indicated the BRIEF accurately classifies groups. These findings confirm compounded behavioral, but not neuropsychological, effects in the AE+ group over the other clinical groups. Parent-report was not correlated with neuropsychological performance in the clinical groups and may provide unique information about neurobehavior. Parent-report measures are clinically useful in predicting alcohol exposure regardless of ADHD. Results contribute to a neurobehavioral profile of prenatal alcohol exposure. (JINS, 2014, 20, 1–13)

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