The convergence of mTOR signaling and ethanol teratogenesis.

Ethanol is one of the most common teratogens and causes of human developmental disabilities. Fetal alcohol spectrum disorders (FASD), which describes the wide range of deficits due to prenatal ethanol exposure, are estimated to affect between 1.1 % and 5.0 % of births in the United States. Ethanol dysregulates numerous cellular mechanisms such as programmed cell death (apoptosis), protein synthesis, autophagy, and various aspects of cell signaling, all of which contribute to FASD. The mechanistic target of rapamycin (mTOR) regulates these cellular mechanisms via sensing of nutrients like amino acids and glucose, DNA damage, and growth factor signaling. Despite an extensive literature on ethanol teratogenesis and mTOR signaling, there has been less attention paid to their interaction. Here, we discuss the impact of ethanol teratogenesis on mTORC1's ability to coordinate growth factor and amino acid sensing with protein synthesis, autophagy, and apoptosis. Notably, the effect of ethanol exposure on mTOR signaling depends on the timing and dose of ethanol as well as the system studied. Overall, the overlap between the functions of mTORC1 and the phenotypes observed in FASD suggest a mechanistic interaction. However, more work is required to fully understand the impact of ethanol teratogenesis on mTOR signaling.

Subcortical volume in middle-aged adults with fetal alcohol spectrum disorders.

Studies of youth and young adults with prenatal alcohol exposure (PAE) have most consistently reported reduced volumes of the corpus callosum, cerebellum and subcortical structures. However, it is unknown whether this continues into middle adulthood or if individuals with PAE may experience premature volumetric decline with aging. Forty-eight individuals with fetal alcohol spectrum disorders (FASD) and 28 healthy comparison participants aged 30 to 65 participated in a 3T MRI session that resulted in usable T1-weighted and T2-weighted structural images. Primary analyses included volumetric measurements of the caudate, putamen, pallidum, cerebellum and corpus callosum using FreeSurfer software. Analyses were conducted examining both raw volumetric measurements and subcortical volumes adjusted for overall intracranial volume (ICV). Models tested for main effects of age, sex and group, as well as interactions of group with age and group with sex. We found the main effects for group; all regions were significantly smaller in participants with FASD for models using raw volumes (P's < 0.001) as well as for models using volumes adjusted for ICV (P's < 0.046). Although there were no significant interactions of group with age, females with FASD had smaller corpus callosum volumes relative to both healthy comparison females and males with FASD (P's < 0.001). As seen in children and adolescents, adults aged 30 to 65 with FASD showed reduced volumes of subcortical structures relative to healthy comparison adults, suggesting persistent impact of PAE. Moreover, the observed volumetric reduction of the corpus callosum in females with FASD could suggest more rapid degeneration, which may have implications for cognition as these individuals continue to age.

Astrocyte extracellular matrix modulates neuronal dendritic development.

Major developmental events occurring in the hippocampus during the third trimester of human gestation and neonatally in altricial rodents include rapid and synchronized dendritic arborization and astrocyte proliferation and maturation. We tested the hypothesis that signals sent by developing astrocytes to developing neurons modulate dendritic development in vivo. We altered neuronal development by neonatal (third trimester-equivalent) ethanol exposure in mice; this treatment increased dendritic arborization in hippocampal pyramidal neurons. We next assessed concurrent changes in the mouse astrocyte translatome by translating ribosomal affinity purification (TRAP)-seq. We followed up on ethanol-inhibition of astrocyte Chpf2 and Chsy1 gene translation because these genes encode for biosynthetic enzymes of chondroitin sulfate glycosaminoglycan (CS-GAG) chains (extracellular matrix components that inhibit neuronal development and plasticity) and have not been explored before for their roles in dendritic arborization. We report that Chpf2 and Chsy1 are enriched in astrocytes and their translation is inhibited by ethanol, which also reduces the levels of CS-GAGs measured by Liquid Chromatography/Mass Spectrometry. Finally, astrocyte-conditioned medium derived from Chfp2-silenced astrocytes increased neurite branching of hippocampal neurons in vitro. These results demonstrate that CS-GAG biosynthetic enzymes in astrocytes regulates dendritic arborization in developing neurons.

Genetic admixture predictors of fetal alcohol spectrum disorders (FASD) in a South African population.

Ancestrally admixed populations are underrepresented in genetic studies of complex diseases, which are still dominated by European-descent populations. This is relevant not only from a representation standpoint but also because of admixed populations' unique features, including being enriched for rare variants, for which effect sizes are disproportionately larger than common polymorphisms. Furthermore, results from these populations may be generalizable to other populations. The South African Cape Coloured (SACC) population is genetically admixed and has one of the highest prevalences of fetal alcohol spectrum disorders (FASD) worldwide. We profiled its admixture and examined associations between ancestry profiles and FASD outcomes using two longitudinal birth cohorts (N=308 mothers, 280 children) designed to examine effects of prenatal alcohol exposure on development. Participants were genotyped via MEGAex array to capture common and rare variants. Rare variants were overrepresented in our SACC cohorts, with numerous polymorphisms being monomorphic in other reference populations (e.g., ∼30,000 and âˆ¼ 221,000 variants in gnomAD European and Asian populations, respectively). The cohorts showed global African (51 %; Bantu and San); European (26 %; Northern/Western); South Asian (18 %); and East Asian (5 %; largely Southern regions) ancestries. The cohorts exhibited high rates of homozygosity (6 %), with regions of homozygosity harboring more deleterious variants when lying within African local-ancestry genomic segments. Both maternal and child ancestry profiles were associated with higher FASD risk, and maternal and child ancestry-by-prenatal alcohol exposure interaction effects were seen on child cognition. Our findings indicate that the SACC population may be a valuable asset to identify novel disease-associated genetic loci for FASD and other diseases.

Fetal alcohol spectrum disorders prevention and clinical guidelines research - workshop report.

It is estimated that up to 1 in 20 people in the United States may have a fetal alcohol spectrum disorder (FASD), or the array of physical, cognitive, emotional, and social disorders caused by exposure to alcohol during prenatal development (May et al., JAMA 319:474-82, 2018). While this condition is present in a broad range of individuals and families, it has not previously been examined in the military community, where cultural factors including an increased prevalence of alcohol misuse may pose a unique set of challenges (Health.mil, Alcohol misuse, 2024).The Uniformed Services University of the Health Sciences (USUHS), in conjunction with FASD United, hosted the second annual Workshop on Fetal Alcohol Spectrum Disorders Prevention and Clinical Guidelines Research on 20 September 2023 in Washington, DC. Organized as part of a four-year, federally-funded health services research initiative on FASD in the U.S. Department of Defense (DoD) Military Health System (MHS), the workshop provided a forum for exploring the initiative's focus and progress; examining current knowledge and practice in the research and clinical spheres; and identifying potential strategies to further improve prevention, screening, diagnosis, interventions, and family support. Building off of the 2022 workshop that covered the state of the science surrounding prenatal alcohol exposure and FASD, the 2023 focused primarily on FASD and efforts aimed at identification and management (Koehlmoos et al., BMC Proc 17 Suppl 12:19, 2023). One hundred and thirty attendees from academia, healthcare, federal agencies, and patient advocacy organizations gathered to share research findings; learn from lived experiences; and discuss initiatives to advance research, screening, and services for at-risk pregnant women as well as families and caregivers supporting individuals with FASD.

Validation of the ND-PAE Diagnosis in Children with Heavy Prenatal Alcohol Exposure.

This study evaluated criteria for neurobehavioral disorder associated with prenatal alcohol exposure (ND-PAE). Kable et al. (Child Psychiatry Hum Dev 55:426, 2022) assessed the validity of this diagnosis in a sample with low exposure to alcohol. The current study expanded this assessment to a sample with a wider age range and heavier alcohol exposure. Data were collected from participants (5-17 years) with prenatal alcohol exposure (PAE) and typically developing controls at six Collaborative Initiative on Fetal Alcohol Spectrum Disorders sites using neuropsychological assessment and caregiver reports. Impairment was tested at 1SD, 1.5SD, and 2SD below the normative average and a modification of the adaptive functioning requirement was tested. Testing impairment at 1SD resulted in the highest endorsement rates in both groups. Our findings replicated the study by Kable et al. and show that current criteria captured a high rate of those with PAE and that requiring fewer adaptive functioning criteria resulted in higher sensitivity to PAE.

Technologies for Supporting Individuals and Caregivers Living With Fetal Alcohol Spectrum Disorder: Scoping Review.

Background: Fetal alcohol spectrum disorder (FASD) is a common developmental disability that requires lifelong and ongoing support but is often difficult to find due to the lack of trained professionals, funding, and support available. Technology could provide cost-effective, accessible, and effective support to those living with FASD and their caregivers. Objective: In this review, we aimed to explore the use of technology available for supporting people living with FASD and their caregivers. Methods: We conducted a scoping review to identify studies that included technology for people with FASD or their caregivers; focused on FASD; used an empirical study design; were published since 2005; and used technology for assessment, diagnosis, monitoring, or support for people with FASD. We searched MEDLINE, Web of Science, Scopus, Embase, APA PsycINFO, ACM Digital Library, JMIR Publications journals, the Cochrane Library, EBSCOhost, IEEE, study references, and gray literature to find studies. Searches were conducted in November 2022 and updated in January 2024. Two reviewers (CZC and HW) independently completed study selection and data extraction. Results: In total, 17 studies exploring technology available for people with FASD showed that technology could be effective at teaching skills, supporting caregivers, and helping people with FASD develop skills. Conclusions: Technology could provide support for people affected by FASD; however, currently there is limited technology available, and the potential benefits are largely unexplored.

Perinatal influences on academic achievement and the developing brain: a scoping systematic review.

Introduction and methods: In this PRISMA-compliant systematic review, we identify and synthesize the findings of research in which neuroimaging and assessments of achievement have been used to examine the relationships among aspects of developmental programming, neurodevelopment, and achievement in reading and mathematics. Results: Forty-seven studies met inclusion criteria. The majority examined the impact of prematurity (n = 32) and prenatal alcohol exposure (n = 13). Several prematurity studies reported a positive correlation between white-matter integrity of callosal fibers and executive functioning and/or achievement, and white matter properties were consistently associated with cognitive and academic performance in preterm and full-term children. Volumetric studies reported positive associations between academic and cognitive abilities and white and gray matter volume in regions such as the insula, putamen, and prefrontal lobes. Functional MRI studies demonstrated increased right-hemispheric language processing among preterm children. Altered activation of the frontoparietal network related to numerical abilities was also reported. Prenatal alcohol exposure studies reported alterations in white matter microstructure linked to deficits in cognitive functioning and academic achievement, including mathematics, reading, and vocabulary skills. Volumetric studies reported reductions in cerebral, cerebellar, and subcortical gray matter volumes associated with decreased scores on measures of executive functioning, attention, working memory, and academic performance. Functional MRI studies demonstrated broad, diffuse activation, reduced activation in canonical regions, and increased activation in non-canonical regions during numeric tasks. Discussion: A preponderance of studies linked prematurity and prenatal alcohol exposure to altered neurodevelopmental processes and suboptimal academic achievement. Limitations and recommendations for future research are discussed. Systematic review registration: Identifier: DOI 10.17605/OSF.IO/ZAN67.

Teachers' needs for an FASD-informed resource: a qualitative interview needs assessment based on the ADAPT-ITT framework.

Background: Fetal alcohol spectrum disorders (FASD) represent a wide range of neurodevelopmental differences associated with prenatal alcohol exposure and are highly prevalent. The current study represents the initial stages in adapting the Families Moving Forward (FMF) Program, an evidence-based behavioral consultation intervention for caregivers of children with FASD, to a website for teachers. Aims: To understand teachers' needs and preferences for an FASD-informed intervention website and to assess the goodness of fit of the FMF Program to teachers and the school setting. Methods: Twenty-three teachers with experience teaching students with FASD were interviewed. Interviews were conducted via Zoom and lasted about 53 minutes on average. Data were transcribed verbatim and analyzed using qualitative content analysis in Dedoose. Results: Three overarching themes represented teachers' needs for an FASD-informed resource: teachers need evidence-based FASD information and strategies, teachers have very little extra time, and the needs of special and general education teachers vary. Teachers were positive about the concepts of the FMF Program and felt they would have good fit. Conclusions: Teachers need an evidence-based FASD-informed intervention that is easy to use, concise, and responsive to varying needs and levels of experience. Results will inform the adaptation process of the FMF Program.

Multigenerational effects of alcohol: A behavioral study in three zebrafish populations.

Fetal alcohol exposure can result in fetal alcohol spectrum disorder (FASD), which encompasses a range of cognitive and behavioral impairments. Although zebrafish have been used as a reliable model to study FASD, little is known about the ontogeny of this disorder and population differences in subsequent generations not directly exposed to alcohol. In this study, we evaluated the behavioral outcomes of zebrafish populations AB, Outbred (OB), and Tubingen (TU), offspring of parents exposed to alcohol during embryonic development. The offspring of adult fish with FASD (exposed to 1 % alcohol at the embryonic stage) was compared to the offspring of unexposed parental fish (0 % alcohol at the embryo phase). The behavioral profile of the offspring was assessed at 6 days post-fertilization (dpf) and 45 dpf. At 6dpf, the AB FASD offspring exhibited hyperactivity and increased time at the edge of the tank, while the TU and OB FASD offspring showed hypoactivity. At 45dpf, TU fish maintained the larval locomotor pattern, characterized by decreased average speed and total distance traveled and increased immobility. However, AB and OB fish did not show alterations in locomotor activity and anxiety-related responses at 45dpf. Our results demonstrate, for the first time, that FASD zebrafish offspring display behavioral differences, which were most evident during the early ontogenetic phase (6dpf) but may vary throughout animal ontogeny. TU fish exhibited the most consistent behavioral pattern across different developmental stages. These findings provide insights into the multigenerational and persistent behavioral consequences of embryonic alcohol exposure in zebrafish. Further research should focus on other features that can be inherited and the development of treatments for the offspring affected by it.

Embryonic ethanol exposure induces oxidative stress and inflammation in zebrafish model: A dose-dependent study.

Alcohol, or ethanol, is a major contributor to detrimental diseases and comorbidities worldwide. Alcohol use during pregnancy intervenes the developing embryos leading to morphological changes, neurocognitive defects, and behavioral changes known as fetal alcohol spectrum disorder (FASD). Zebrafish have been used as a model to study FASD; however, the mechanism and the impact of ethanol on oxidative stress and inflammation in the zebrafish FASD model remain unexplored. Hence, we exposed zebrafish embryos to different concentrations of ethanol (0 %, 0.5 %, 1.0 %, 1.25 %, and 1.5 % ethanol (v/v)) at 4-96 hours post-fertilization (hpf) to study and characterize the ethanol concentration for the FASD model to induce oxidative stress and inflammation. Here, we studied the survival rate and developmental toxicity parameters at different time points and measured oxidative stress, reactive oxygen species (ROS) generation, apoptosis, and pro-inflammatory gene expression in zebrafish larvae. Our findings indicate that ethanol causes various developmental abnormalities, including decreased survival rate, spontaneous tail coiling, hatching rate, heart rate, and body length, associated with increased malformation. Further, ethanol exposure induced oxidative stress by increasing lipid peroxidation and nitric oxide production and decreasing glutathione levels. Subsequently, ethanol increased ROS generation, apoptosis, and pro-inflammatory gene (TNF-α and IL-1ß) expression in ethanol exposed larvae. 1.25 % and 1.5 % ethanol had significant impacts on zebrafish larvae in all studied parameters. However, 1.5 % ethanol showed decreased survival rate and increased malformations. Overall, 1.25 % ethanol is the ideal concentration to study the oxidative stress and inflammation in the zebrafish FASD model.

Positive behavior support (PBS) with children with fetal alcohol spectrum disorders: Characterizing caregivers' use of PBS using follow-up clinical trial data.

BACKGROUND: Fetal alcohol spectrum disorders (FASD) are associated with neurodevelopmental challenges leading to difficulties with everyday life tasks. The Families Moving Forward (FMF) Program teaches caregivers to use positive behavior support (PBS), integrated with other techniques. However, it is unknown how caregivers retain and use these PBS strategies after the intervention. METHODS: About 4.5 months after completing the FMF Program, twenty-three caregivers of children with FASD aged 4-12 were interviewed about problem behaviors targeted during the FMF Program and their continued use of PBS strategies. Interviews were recorded and coded thematically by a five-coder team. Higher-level pattern codes were developed to facilitate themes across descriptive codes. RESULTS: Caregivers commonly targeted task incompletion and rule breaking, and problem behaviors were often complex or combined. Caregivers identified environmental and interpersonal triggers for problem behavior. They used many accommodations to prevent problem behaviors, most often related to task or environment simplification. Caregivers also used consequence-based strategies. CONCLUSIONS: This study is the first to characterize caregivers' use of PBS strategies for children with FASD using mixed methods. Problem behaviors such as rule breaking were more difficult to target. Caregivers found most success when using a combination of multiple different accommodations per problem behavior. WHAT THIS PAPER ADDS: This is the first study to use mixed methods to characterize how caregivers of children with fetal alcohol spectrum disorders (FASD) use positive behavior support (PBS) strategies to target problem behavior after completion of the empirically validated Families Moving Forward (FMF) Program. Among other techniques involved in the FMF Program, PBS strategies are taught to caregivers and are used to target two distinct, caregiver-identified problem behaviors. This data provides essential information about behaviors responsive to PBS supports, for children with FASD, to inform clinical intervention and research. Notably, multiple problem behaviors often occurred together, emphasizing complexity of behavior challenges in this population and the resulting need for individualized supports. This study is the first to describe commonly observed triggers (antecedents) and commonly used supports (accommodations) from the perspective of caregivers of children with FASD. Importantly, results indicate that use of a wide variety of accommodations, or antecedent-based strategies, are effective in supporting behavior in children with FASD. However, success was most common when caregivers used multiple accommodations for any given concerning behavior. Findings represent 'real-world' strategies caregivers use to support adaptive behavior in their children several months after completion of the FMF Program, suggesting these strategies are applicable to clinical practice.

My Health Coach: Community members' perspectives on a mobile health tool for adults with fetal alcohol spectrum disorders.

Objectives: Fetal alcohol spectrum disorders (FASD) affect the health and development of people across the lifespan. Adults with FASD experience significant barriers to care. Accessible and scalable solutions are needed. In partnership with members of the International Adult Leadership Collaborative of FASD Changemakers, an international group of adults with FASD, we developed a mobile health (mHealth) application based on self-determination theory (SDT), called "My Health Coach," to promote self-management and health advocacy. Methods: This project follows an established user-centered design approach to app development and evaluation, allowing for feedback loops promoting iterative change. Research staff and ALC members co-led online focus groups (n = 26) and an online follow-up survey (n = 26) with adults with FASD to elicit feedback on completed design prototypes. Focus group transcriptions and surveys underwent systemic thematic and theoretical framework analysis. Results: Analyses show overall positive impressions of the My Health Coach app. Participants were enthusiastic about the proposed features and tools the app will provide. Discussions and free responses revealed SDT constructs (autonomy, competence, relatedness) are a strong fit with participants' perceived outcomes shared in their evaluation of the prototype. Interesting recommendations were made for additional features that would further promote SDT constructs. Conclusions: This project demonstrates advantages of community-engaged partnerships in FASD research. Adults with FASD have a strong interest in scalable mHealth tools and described the acceptability of our initial design. App features and tools promoted SDT constructs.

Analysis of alcohol-metabolizing enzymes genetic variants and RAR/RXR expression in patients diagnosed with fetal alcohol syndrome: a case-control study.

Understanding the mechanisms underlying alcohol metabolism and its regulation, including the effect of polymorphisms in alcohol-metabolizing enzymes, is crucial for research on Fetal Alcohol Spectrum Disorders. The aim of this study was to identify specific single nucleotide polymorphisms in key alcohol-metabolizing enzymes in a cohort of 71 children, including children with fetal alcohol syndrome, children prenatally exposed to ethanol but without fetal alcohol spectrum disorder, and controls. We hypothesized that certain genetic variants related to alcohol metabolism may be fixed in these populations, giving them a particular alcohol metabolism profile. In addition, the difference in certain isoforms of these enzymes determines their affinity for alcohol, which also affects the metabolism of retinoic acid, which is key to the proper development of the central nervous system. Our results showed that children prenatally exposed to ethanol without fetal alcohol spectrum disorder traits had a higher frequency of the ADH1B*3 and ADH1C*1 alleles, which are associated with increased alcohol metabolism and therefore a protective factor against circulating alcohol in the fetus after maternal drinking, compared to FAS children who had an allele with a lower affinity for alcohol. This study also revealed the presence of an ADH4 variant in the FAS population that binds weakly to the teratogen, allowing increased circulation of the toxic agent and direct induction of developmental abnormalities in the fetus. However, both groups showed dysregulation in the expression of genes related to the retinoic acid pathway, such as retinoic acid receptor and retinoid X receptor, which are involved in the development, regeneration, and maintenance of the nervous system. These findings highlight the importance of understanding the interplay between alcohol metabolism, the retinoic acid pathway and genetic factors in the development of fetal alcohol syndrome.

Risk and Resilience Variants in the Retinoic Acid Metabolic and Developmental Pathways Associated with Risk of FASD Outcomes.

Fetal Alcohol Spectrum Disorder (FASD) is a common neurodevelopmental disorder that affects an estimated 2-5% of North Americans. FASD is induced by prenatal alcohol exposure (PAE) during pregnancy and while there is a clear genetic contribution, few genetic factors are currently identified or understood. In this study, using a candidate gene approach, we performed a genetic variant analysis of retinoic acid (RA) metabolic and developmental signaling pathway genes on whole exome sequencing data of 23 FASD-diagnosed individuals. We found risk and resilience alleles in ADH and ALDH genes known to normally be involved in alcohol detoxification at the expense of RA production, causing RA deficiency, following PAE. Risk and resilience variants were also identified in RA-regulated developmental pathway genes, especially in SHH and WNT pathways. Notably, we also identified significant variants in the causative genes of rare neurodevelopmental disorders sharing comorbidities with FASD, including STRA6 (Matthew-Wood), SOX9 (Campomelic Dysplasia), FDG1 (Aarskog), and 22q11.2 deletion syndrome (TBX1). Although this is a small exploratory study, the findings support PAE-induced RA deficiency as a major etiology underlying FASD and suggest risk and resilience variants may be suitable biomarkers to determine the risk of FASD outcomes following PAE.

In Vivo Administration of Phosphatidic Acid, a Direct Alcohol Target Rescues Fetal Growth Restriction and Maternal Uterine Artery Dysfunction in Rat FASD Model.

Fetal growth restriction is a hallmark of Fetal Alcohol Syndrome (FAS) and is accompanied by maternal uterine circulatory maladaptation. FAS is the most severe form of Fetal Alcohol Spectrum Disorder (FASD), a term for the range of conditions that can develop in a fetus when their pregnant mother consumes alcohol. Alcohol exerts specific direct effects on lipids that control fundamental developmental processes. We previously demonstrated that direct in vitro application of phosphatidic acid (PA, the simplest phospholipid and a direct target of alcohol exposure) to excised uterine arteries from alcohol-exposed rats improved vascular function, but it is unknown if PA can rescue end organ phenotypes in our FASD animal model. Pregnant Sprague-Dawley rats (n = 40 total dams) were gavaged daily from gestational day (GD) 5 to GD 19 with alcohol or maltose dextrin, with and without PA supplementation, for a total of four unique groups. To translate and assess the beneficial effects of PA, we hypothesized that in vivo administration of PA concomitant with chronic binge alcohol would reverse uterine artery dysfunction and fetal growth deficits in our FASD model. Mean fetal weights and placental efficiency were significantly lower in the binge alcohol group compared with those in the control (p < 0.05). However, these differences between the alcohol and the control groups were completely abolished by auxiliary in vivo PA administration with alcohol, indicating a reversal of the classic FAS growth restriction phenotype. Acetylcholine (ACh)-induced uterine artery relaxation was significantly impaired in the uterine arteries of chronic in vivo binge alcohol-administered rats compared to the controls (p < 0.05). Supplementation of PA in vivo throughout pregnancy reversed the alcohol-induced vasodilatory deficit; no differences were detected following in vivo PA administration between the pair-fed control and PA alcohol groups. Maximal ACh-induced vasodilation was significantly lower in the alcohol group compared to all the other treatments, including control, control PA, and alcohol PA groups (p < 0.05). When analyzing excitatory vasodilatory p1177-eNOS, alcohol-induced downregulation of p1177-eNOS was completely reversed following in vivo PA supplementation. In summary, these novel data utilize a specific alcohol target pathway (PA) to demonstrate a lipid-based preventive strategy and provide critical insights important for the development of translatable interventions.

An examination of executive functioning in adolescents with FASD in a self-regulation intervention.

Adolescents with Fetal Alcohol Spectrum Disorder (FASD) often have challenges with executive functioning (EF), which impacts their ability to self-regulate. In this study, 23 adolescents with FASD completed a self-regulation intervention. The intervention was a manualized Teen Adaptation of the Alert Program®. A nonrandomized waitlist control design was used, and participants completed pre- and post-testing using performance-based measures of EF, and rating scales of EF were completed by caregivers. Results were analyzed three ways; 1) intervention and waitlist control group comparison, 2) whole sample pre-and post- test comparison, and 3) using Reliable Change Indexes to examine individual-level clinically relevant changes. No significant intervention effects were found when comparing the intervention and waitlist control groups. A significant difference was found on a measure of verbal inhibition when total sample pre-and post-test scores were compared. Using Reliable Change Index analysis, 30% participants showed reliable change in the direction of improvement on direct measures of EF, and 57% demonstrated reliable change in the direction of improvement on rating scales. This research study underscores the importance of investigating both individual and group level changes when analyzing data, as well as using reliable change to understand clinically meaningful effects that may be otherwise masked. These findings highlight the potential of the SR intervention to positively impact EF in adolescents with FASD. This study contributes to the growing literature that demonstrates the potential of individuals with FASD to benefit from direct intervention.

Prevalence of co-occurring diagnoses in people exposed to alcohol prenatally: Findings from a meta-analysis.

BACKGROUND: Individuals with prenatal alcohol exposure (PAE) commonly experience co-occurring diagnoses, which are often overlooked and misdiagnosed and have detrimental impacts on accessing appropriate services. The prevalence of these co-occurring diagnoses varies widely in the existing literature and has not been examined in PAE without an FASD diagnosis. METHOD: A search was conducted in five databases and the reference sections of three review papers, finding a total of 2180 studies. 57 studies were included in the final analysis with a cumulative sample size of 29,644. Bayesian modeling was used to determine aggregate prevalence rates of co-occurring disorders and analyze potential moderators. RESULTS: 82 % of people with PAE had a co-occurring diagnosis. All disorders had a higher prevalence in individuals with PAE than the general population with attention deficit hyperactivity disorder, learning disorder, and intellectual disability (ID) being the most prevalent. Age, diagnostic status, and sex moderated the prevalence of multiple disorders. LIMITATIONS: While prevalence of disorders is crucial information, it does not provide a direct representation of daily functioning and available supports. Results should be interpreted in collaboration with more individualized research to provide the most comprehensive representation of the experience of individuals with PAE. CONCLUSIONS: Co-occurring diagnoses are extremely prevalent in people with PAE, with older individuals, females, and those diagnosed with FASD being most at risk for having a co-occurring disorder. These findings provide a more rigorous examination of the challenges faced by individuals with PAE than has existed in the literature, providing clinicians with information to ensure early identification and effective treatment of concerns to prevent lifelong challenges.

"Taking part in the project has really changed our experience as a family" investigating parents' experience of participation in a study to screen for fetal alcohol spectrum disorder.

Background: Screening children for developmental disorders presents unique ethical and methodological challenges, particularly with disorders associated with high levels of shame and stigma. Fetal alcohol spectrum disorder (FASD) is a neurodevelopmental condition resulting from prenatal alcohol exposure. The potential distress caused by informing parents that their child may have FASD has been cited as a significant barrier to conducting such studies. However, limited research has investigated the impact of screening for FASD on parents and children. Aims: This exploratory study aimed to examine the experiences of a small sample of parents participating in an active case ascertainment prevalence study screening for FASD in Greater Manchester, UK (ADD-GM study). Methods: Interviews were conducted with six parents, whose children aged 8-10 years, underwent screening (including three cases of FASD). Thematic analysis was performed on the collected data to identify key themes and patterns. Results: The analysis revealed that parents perceived participation in the study as worthwhile, and their children either enjoyed or were indifferent to the process of data collection. Parents of children identified with FASD reported that although the results were surprising, they did not find the experience overly distressing. Conclusion: The findings suggest that parents generally view participation positively and perceive limited negative impact. These insights contribute to a better understanding of the challenges and benefits associated with screening children for FASD.

Influence of childhood trauma and traumatic stress on a woman's risk of having a child with a fetal alcohol spectrum disorder.

BACKGROUND: Maternal risk factors for having a child diagnosed on the fetal alcohol spectrum disorders (FASD) continuum are complex and include not only the quantity, frequency, and timing of alcohol use but also a woman's physical stature, socio-economic status, and pregnancy-related factors. Exposure to trauma may predispose women to a range of physiological and mental disorders. A woman's mental and physical health may in turn influence her probability of having a child with FASD. This study investigated the role of maternal childhood trauma and lifetime traumatic stress on prenatal alcohol consumption and on the risk of having a child with FASD. METHODS: A nested, case-control study was conducted for maternal risk assessment. Study participants were mothers of first-grade learners from five rural communities in the Western Cape Province of South Africa who were assessed for FASD. Face-to-face surveys were conducted, which included mental health and trauma assessment questionnaires. RESULTS: In logistic regression analyses, higher maternal childhood trauma scores were associated with an increased likelihood of having a child diagnosed with FASD, although the increase in risk was modest (OR = 1.014, p = 0.015). In addition, structural equation modeling investigated relationships between maternal drinking, childhood trauma, traumatic stress, and a child's FASD diagnosis. Traumatic stress and drinking during pregnancy, but not lifetime alcohol use, were associated with maternal childhood trauma. Lifetime alcohol use influenced drinking during pregnancy, which in turn was significantly associated with having a child diagnosed on the continuum of FASD. CONCLUSION: No direct influence of maternal childhood trauma on FASD diagnosis could be demonstrated. However, maternal trauma may indirectly contribute to the risk of having a child diagnosed with FASD.