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Effects of prenatal alcohol exposure (PAE): insights into FASD using mouse models of PAE.

ABSTRACT: The potential impact of prenatal alcohol exposure (PAE) varies considerably among exposed individuals, with some displaying serious alcohol-related effects and many others showing few or no overt signs of fetal alcohol spectrum disorder (FASD). In animal models, variables such as nutrition, genetic background, health, other drugs, and stress, as well as dosage, duration, and gestational timing of exposure to alcohol can all be controlled in a way that is not possible in a clinical situation. In this review we examine mouse models of PAE and focus on those with demonstrated craniofacial malformations, abnormal brain development, or behavioral phenotypes that may be considered FASD-like outcomes. Analysis of these data should provide a valuable tool for researchers wishing to choose the PAE model best suited to their research questions or to investigate established PAE models for FASD comorbidities. It should also allow recognition of patterns linking gestational timing, dosage, and duration of PAE, such as recognizing that binge alcohol exposure(s) during early gestation can lead to severe FASD outcomes. Identified patterns could be particularly insightful and lead to a better understanding of the molecular mechanisms underlying FASD.

SUBMITTER: Petrelli B

PROVIDER: S-EPMC5991836 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Effects of prenatal alcohol exposure (PAE): insights into FASD using mouse models of PAE.

Petrelli Berardino B Weinberg Joanne J Hicks Geoffrey G GG

Biochemistry and cell biology = Biochimie et biologie cellulaire 20180125 2

The potential impact of prenatal alcohol exposure (PAE) varies considerably among exposed individuals, with some displaying serious alcohol-related effects and many others showing few or no overt signs of fetal alcohol spectrum disorder (FASD). In animal models, variables such as nutrition, genetic background, health, other drugs, and stress, as well as dosage, duration, and gestational timing of exposure to alcohol can all be controlled in a way that is not possible in a clinical situation. In ...[more]

PMID: 29370535

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Project description:BackgroundPrenatal alcohol exposure (PAE) is associated with growth deficits and neurodevelopmental impairment including foetal alcohol spectrum disorder (FASD). Difficulties with oral and written communication skills are common among children with PAE; however, less is known about how communication skills of adolescents who have PAE compare with those who do not. Adolescence is a critical time for development, supporting the transition into adulthood, but it is considered a high-risk period for those with FASD.AimsWe conducted a systematic review to synthesize evidence regarding oral and written communication skills of adolescents with PAE or FASD and how they compare with those with no PAE.Methods & proceduresA comprehensive search strategy used seven databases: Cochrane Library, Cinahl, Embase, Medline, PsycInfo, Eric and Web of Science. Included studies reported on at least one outcome related to oral and written communication for a PAE (or FASD) group as well as a no/low PAE group, both with age ranges of 10-24 years. Quality assessment was undertaken.Main contributionCommunication skills most often assessed in the seven studies included in this review were semantic knowledge, semantic processing, and verbal learning and memory. These communication skills, in addition to reading and spelling, were commonly weaker among adolescents with PAE compared with those with no/low PAE. However, the findings were inconsistent across studies, and studies differed in their methodologies.Conclusions & implicationsOur results emphasize that for adolescents with PAE, communication skills in both oral and written modalities should be comprehensively understood in assessment and when planning interventions. A key limitation of the existing literature is that comparison groups often include some participants with a low level of PAE, and that PAE definitions used to allocate participants to groups differ across studies.What this paper addsWhat is already known on the subject PAE and FASD are associated with deficits in oral and written communication skills. Studies to date have mostly focused on children with a FASD diagnosis as well as combined groups of children and adolescents with FASD or PAE. There is a gap in what is known about oral and written communication skills of adolescents, specifically, who have PAE or FASD. This has implications for the provision of assessment and supports during a period of increased social and academic demands. What this study adds to existing knowledge This review provides systematic identification, assessment and synthesis of the current literature related to oral and written communication skills of adolescents with PAE compared with those with no/low PAE. The review revealed a small knowledge base with inconsistent methodologies and findings across studies. However, the findings overall highlight that adolescents with PAE have weaker skills in oral and written language than those with no/low PAE. Results are discussed in relation to education, social and emotional well-being, and forensic contexts. What are the potential or actual clinical implications of this work? Findings emphasize that for adolescents with PAE, comprehensive assessment of both oral and written communication skills, through both standardized and functional tasks, should be undertaken. Speech-language pathologists have a key role in assessment with individuals who have PAE.

Project description:Craniofacial bone dysmorphology is an important but under-explored potential diagnostic feature of fetal alcohol spectrum disorders. This study used longitudinal MicroCT 3D imaging to examine the effect of prenatal alcohol exposure on craniofacial bone growth in a mouse model. C57BL/6J dams were divided into 3 groups: alcohol 4.2% v/v in PMI® liquid diet (ALC), 2 weeks prior to and during pregnancy from embryonic (E) days 7-E16; pair-fed controls (PF), isocalorically matched to the ALC group; chow controls (CHOW), given ad libitum chow and water. The MicroCT scans were performed on pups on postnatal days 7 (P7) and P21. The volumes of the neurocranium (volume encased by the frontal, parietal, and occipital bones) and the viscerocranium (volume encased by the mandible and nasal bone), along with total skull bone volume, head size, and head circumference were evaluated using general linear models and discriminant analyses. The pups in the alcohol-treated group, when compared to the chow-fed controls (ALC vs CHOW) and the isocaloric-fed controls (ALC vs PF), showed differences in head size and circumference at P7 and P21, the total skull volume and parietal bone volume at P7, and volume of all the tested bones except nasal at P21. There was a growth trend of ALC < CHOW and ALC < PF. While covarying for gender and head size or circumference, the treatment affected the total skull and mandible at P7 (ALC > CHOW), and the total skull, parietal bone, and occipital bone at P21 (ALC < CHOW, ALC < PF). While covarying for the P7 measures, the treatment affected only the 3 neurocranial bones at P21 (ALC < CHOW, ALC < PF). Discriminant analysis sensitively selected between ALC and CHOW (AUC = 0.967), between ALC and PF (AUC = 0.995), and between PF and CHOW (AUC = 0.805). These results supported our hypothesis that craniofacial bones might be a reliable and sensitive indicator for the diagnosis of prenatal alcohol exposure. Significantly, we found that the neurocranium (upper skull) was more sensitive to alcohol than the viscerocranium (face).

Project description:Heavy prenatal alcohol exposure and attention-deficit/hyperactivity disorder (ADHD) are associated with adaptive behavior deficits. This study examined the interaction between these 2 factors on parent ratings of adaptive behavior.As part of a multisite study, primary caregivers of 317 children (8 to 16 years, M = 12.38) completed the Vineland Adaptive Behavior Scales-Second Edition (VABS-II). Four groups of subjects were included: children with prenatal alcohol exposure with ADHD (AE+, n = 82), children with prenatal alcohol exposure without ADHD (AE-, n = 34), children with ADHD (ADHD, n = 71), and control children (CON, n = 130). VABS-II domain scores (Communication, Daily Living Skills, Socialization) were examined using separate 2 (Alcohol Exposure [AE]) × 2 (ADHD diagnosis) between-subjects analyses of covariance.There were significant main effects of AE (p < 0.001) and ADHD (p < 0.001) on all VABS-II domains; alcohol-exposed children had lower scores than children without prenatal alcohol exposure and children with ADHD had lower scores than those without ADHD. There was a significant AE × ADHD interaction effect for Communication, F(1, 308) = 7.49, p = 0.007, partial ?(2) = 0.024, but not Daily Living Skills or Socialization domains (ps > 0.27). Follow-up analyses in the Communication domain indicated the effects of ADHD were stronger in comparison subjects (ADHD vs. CON) than exposed subjects (AE+ vs. AE-), and the effects of alcohol exposure were stronger in subjects without ADHD (AE- vs. CON) than in subjects with ADHD (AE+ vs.As found previously, both prenatal alcohol exposure and ADHD increase adaptive behavior deficits in all domains. However, these 2 factors interact to cause the greatest impairment in children with both prenatal alcohol exposure and ADHD for communication abilities. These results further demonstrate the deleterious effects of prenatal alcohol exposure and broaden our understanding of how ADHD exacerbates behavioral outcomes in this population.

Project description:BACKGROUND:Our objective is to help clinicians detect the facial effects of prenatal alcohol exposure by developing computer-based tools for screening facial form. METHODS:All 415 individuals considered were evaluated by expert dysmorphologists and categorized as (i) healthy control (HC), (ii) fetal alcohol syndrome (FAS), or (iii) heavily prenatally alcohol exposed (HE) but not clinically diagnosable as FAS; 3D facial photographs were used to build models of facial form to support discrimination studies. Surface curvature-based delineations of facial form were introduced. RESULTS:(i) Facial growth in FAS, HE, and control subgroups is similar in both cohorts. (ii) Cohort consistency of agreement between clinical diagnosis and HC-FAS facial form classification is lower for midline facial regions and higher for nonmidline regions. (iii) Specific HC-FAS differences within and between the cohorts include: for HC, a smoother philtrum in Cape Coloured individuals; for FAS, a smoother philtrum in Caucasians; for control-FAS philtrum difference, greater homogeneity in Caucasians; for control-FAS face difference, greater homogeneity in Cape Coloured individuals. (iv) Curvature changes in facial profile induced by prenatal alcohol exposure are more homogeneous and greater in Cape Coloureds than in Caucasians. (v) The Caucasian HE subset divides into clusters with control-like and FAS-like facial dysmorphism. The Cape Coloured HE subset is similarly divided for nonmidline facial regions but not clearly for midline structures. (vi) The Cape Coloured HE subset with control-like facial dysmorphism shows orbital hypertelorism. CONCLUSIONS:Facial curvature assists the recognition of the effects of prenatal alcohol exposure and helps explain why different facial regions result in inconsistent control-FAS discrimination rates in disparate ethnic groups. Heavy prenatal alcohol exposure can give rise to orbital hypertelorism, supporting a long-standing suggestion that prenatal alcohol exposure at a particular time causes increased separation of the brain hemispheres with a concomitant increase in orbital separation.

Project description:BackgroundIn animal models, it is possible to induce different alcohol-related dysmorphic abnormalities based on the timing of prenatal alcohol exposure (PAE). Our objective was to assess whether patterns of PAE differentially predict alcohol-related dysmorphic features in 415 infants.MethodsWe analyzed a prospective pregnancy cohort in western Ukraine enrolled between 2008 and 2014. Five distinct trajectories were previously identified to summarize PAE: (i) minimal/no PAE (n = 253), (ii) low/moderate PAE with reduction early in gestation (n = 78), (iii) low/moderate sustained PAE (n = 20), (iv) moderate/high PAE with reduction early in gestation (n = 45), and (v) high sustained PAE (n = 19). A dysmorphology examination of body size, 3 cardinal, and 15 noncardinal dysmorphic features was performed at approximately 6 to 12 months of age. A modified dysmorphology score was created based on previously published weights. Univariate comparisons were made between each dysmorphic feature and trajectory group. Features that differed by trajectory group were assessed in multivariable analyses. Models were adjusted for maternal age, prenatal vitamin use, socioeconomic status, smoking, and child's age at dysmorphology examination, with censoring weights for losses to follow-up.ResultsThe 3 highest trajectories predicted total dysmorphology score, with larger effects in sustained exposure groups. Cardinal features: The 3 highest trajectories were each associated with a 2- to 3-fold increased risk of having 2 + cardinal facial features. When assessed individually, there were no consistent associations between the individual trajectories and each cardinal feature. Noncardinal features: The 3 highest trajectories were associated with increased risk of hypotelorism. Only the highest trajectory was associated with heart murmur. The highest trajectory predicted <10th centile for sex and age on height, weight, and head circumference; and moderate/high with reduction trajectory also predicted height.ConclusionsWhile we did not observe differential results based on specific trajectories of exposure, findings support the wide range of dysmorphic features associated with PAE, particularly at high and sustained levels.

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Effects of prenatal alcohol exposure (PAE): insights into FASD using mouse models of PAE.

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Effects of prenatal alcohol exposure (PAE): insights into FASD using mouse models of PAE.

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