Oxidative Effects in Early Stages of Embryo Development Due to Alcohol Consumption.

Alcohol, a widely consumed drug, exerts significant toxic effects on the human organism. This review focuses on its impact during fetal development, when it leads to a spectrum of disorders collectively termed Fetal Alcohol Spectrum Disorders (FASD). Children afflicted by FASD exhibit distinct clinical manifestations, including facial dysmorphism, delayed growth, and neurological and behavioral disorders. These behavioral issues encompass diminished intellectual capacity, memory impairment, and heightened impulsiveness. While the precise mechanisms underlying alcohol-induced fetal damage remain incompletely understood, research indicates a pivotal role for reactive oxygen species (ROS) that are released during alcohol metabolism, inciting inflammation at the cerebral level. Ethanol metabolism amplifies the generation of oxidant molecules, inducing through alterations in enzymatic and non-enzymatic systems responsible for cellular homeostasis. Alcohol consumption disrupts endogenous enzyme activity and fosters lipid peroxidation in consumers, potentially affecting the developing fetus. Addressing this concern, administration of metformin during the prenatal period, corresponding to the third trimester of human pregnancy, emerges as a potential therapeutic intervention for mitigating FASD. This proposed approach holds promise for ameliorating the adverse effects of alcohol exposure on fetal development and warrants further investigation.

Fetal alcohol spectrum disorder diagnostic clinic capacity in Canadian Provinces and territories.

This study investigated the diagnostic capacity for Fetal Alcohol Spectrum Disorder (FASD) in multidisciplinary clinics across several provincial and one territorial jurisdictions of Canada: Alberta, British Columbia, Manitoba, Ontario and Northwest Territories. The data were collected directly from clinics capable of providing diagnoses of FASD and examined annual capacity for the assessment and diagnosis of FASD per year from 2015 to 2019. In total, 58 FASD diagnostic clinics were identified and 33 clinics participated in this survey. The study identified inadequate FASD diagnostic capacity in all participating jurisdictions. Based on the findings and the current population sizes, it is estimated that 98% of individuals with FASD are undiagnosed or misdiagnosed in Canada. Wait times for FASD diagnosis ranged from 1 month to 4.5 years across participating jurisdictions. The annual FASD diagnostic capacity in the select provinces and territories require at least a 67-fold increase per year.

An overview of current advances in perinatal alcohol exposure and pathogenesis of fetal alcohol spectrum disorders.

The adverse use of alcohol is a serious global public health problem. Maternal alcohol consumption during pregnancy usually causes prenatal alcohol exposure (PAE) in the developing fetus, leading to a spectrum of disorders known as fetal alcohol spectrum disorders (FASD) and even fetal alcohol syndrome (FAS) throughout the lifelong sufferers. The prevalence of FASD is approximately 7.7 per 1,000 worldwide, and is even higher in developed regions. Generally, Ethanol in alcoholic beverages can impair embryonic neurological development through multiple pathways leading to FASD. Among them, the leading mechanism of FASDs is attributed to ethanol-induced neuroinflammatory damage to the central nervous system (CNS). Although the underlying molecular mechanisms remain unclear, the remaining multiple pathological mechanisms is likely due to the neurotoxic damage of ethanol and the resultant neuronal loss. Regardless of the molecular pathway, the ultimate outcome of the developing CNS exposed to ethanol is almost always the destruction and apoptosis of neurons, which leads to the reduction of neurons and further the development of FASD. In this review, we systematically summarize the current research progress on the pathogenesis of FASD, which hopefully provides new insights into differential early diagnosis, treatment and prevention for patents with FASD.

Fetal alcohol spectrum disorder and attention deficit hyperactivity disorder stimulant trial in children: an N-of-1 pilot trial to compare stimulant to placebo (FASST): protocol.

INTRODUCTION: Fetal alcohol spectrum disorder (FASD) is a neurodevelopmental disorder caused by alcohol exposure during pregnancy. FASD is associated with neurodevelopmental deviations, and 50%-94% of children with FASD meet the Diagnostic and Statistical Manual of Mental Disorders-fifth edition diagnostic criteria for attention deficit hyperactivity disorder (ADHD). There is a paucity of evidence around medication efficacy for ADHD symptoms in children with FASD. This series of N-of-1 trials aims to provide pilot data on the feasibility of conducting N-of-1 trials in children with FASD and ADHD. METHODS AND ANALYSIS: A pilot N-of-1 randomised trial design with 20 cycles of stimulant and placebo (four cycles of 2-week duration) for each child will be conducted (n=20) in Melbourne, Australia.Feasibility and tolerability will be assessed using recruitment and retention rates, protocol adherence, adverse events and parent ratings of side effects. Each child's treatment effect will be determined by analysing teacher ADHD ratings across stimulant and placebo conditions (Wilcoxon rank). N-of-1 data will be aggregated to provide an estimate of the cohort treatment effect as well as individual-level treatment effects. We will assess the sample size and number of cycles required for a future trial. Potential mediating factors will be explored to identify variables that might be associated with treatment response variability. ETHICS AND DISSEMINATION: The study was approved by the Hospital and Health Service Human Research Ethics Committee (HREC/74678/MonH-2021-269029), Monash (protocol V6, 25 June 2023).Individual outcome data will be summarised and provided to participating carers and practitioners to enhance care. Group-level findings will be presented at a local workshop to engage stakeholders. Findings will be presented at national and international conferences and published in peer-reviewed journals. All results will be reported so that they can be used to inform prior information for future trials. TRIAL REGISTRATION NUMBER: NCT04968522.

Prevention of alcohol exposed pregnancies in Europe: the FAR SEAS guidelines.

INTRODUCTION: Drinking during pregnancy is the leading cause of birth defects and child developmental disorders in Europe. The adverse effects of drinking during pregnancy may include physical, behavioural and cognitive problems, known collectively as fetal alcohol spectrum disorders (FASD). Evidence-based comprehensive recommendations at the European level on how to implement preventive and treatment policies to reduce alcohol-exposed pregnancies are needed. FAR SEAS, a tendered service contract (number 20,187,106) awarded by the European Commission, aimed at developing guidelines to respond to this knowledge gap. METHODS: FAR SEAS recommendations were built on (1) a two-phase review of interventions, (2) an international expert consultation, and (3) a pilot study on prevention of FASD conducted in the Mazovia region of Poland. The review of interventions included nineteen electronic open access databases, several repositories of grey literature and a key informant consultation covering most European Union (EU) countries and an additional guidelines search. After triangulating sources, 94 records were collected. Experts contributed in the design of the research questions, addressing the gaps in the literature and reviewing the recommendations formulated. The Polish pilot added nuances from real world practice to the formulated recommendations, resulting in the final set of guidelines for dissemination. RESULTS: The FAR SEAS Guidelines comprise 23 recommendations grouped into different topics areas of policies, communication strategies, screening, brief intervention and referral to treatment, treatment and social services. The recommendations highlight the need to respect women's autonomy and avoid discrimination and stigmatization; using universal screening for women of childbearing age, including detection of other psychosocial risks (such as domestic violence); and individualized, comprehensive and multidisciplinary supportive interventions for those who require it, such as those with alcohol use disorders, including women's partners. Policies to prevent FASD should be multicomponent, and public health communication should combine information about the risks together with self-efficacy messages to promote changes. CONCLUSIONS: The FAR SEAS guidelines are a tool to support policy-makers and service managers in implementing effective programmes to reduce prenatal alcohol exposure among general and at-risk population groups. FASD prevention has to involve comprehensive and multi-level evidence-based policies and practice, with services and activities tailored to the needs of women at differing levels of risk, and with due attention to reducing stigma.

Reach, Acceptability, and Sustainability of the Native Changing High-Risk Alcohol Use and Increasing Contraception Effectiveness Study (CHOICES) Intervention: A Qualitative Evaluation of an Alcohol-Exposed Pregnancy Prevention Program.

American Indian (AI) women are at risk of alcohol-exposed pregnancy (AEP) due to the higher prevalence of alcohol use disorders (AUDs) and risky drinking. The Native Changing High-Risk Alcohol Use and Increasing Contraception Effectiveness Study (Native CHOICES) was implemented in partnership with a Northern Plains Tribal community to address the effectiveness of a brief, motivational interviewing-based intervention to reduce AEP risk among adult AI women. A subgroup of the participants shared their perspectives in a qualitative interview conducted following the completion of the six-month post-baseline data collection. These interviews solicited participant perspectives on the Native CHOICES intervention and its satisfaction, reach, acceptability, and sustainability. The participants were delighted with Native CHOICES, felt the intervention helped them learn about AEP prevention and goal setting, learned valuable lessons, and believed Native CHOICES would be well-received by other women in their community and should be continued. The participants also shared how the COVID-19 pandemic affected their choices about drinking and birth control. The findings showed the receptivity to and acceptance of Native CHOICES among AI women. The interview findings offered a glimpse into the effectiveness of Native CHOICES and how it contributed to participants making healthier choices surrounding drinking and sexual health.

Developmental Ethanol Exposure Impacts Purkinje Cells but Not Microglia in the Young Adult Cerebellum.

Fetal alcohol spectrum disorders (FASD) caused by developmental ethanol exposure lead to cerebellar impairments, including motor problems, decreased cerebellar weight, and cell death. Alterations in the sole output of the cerebellar cortex, Purkinje cells, and central nervous system immune cells, microglia, have been reported in animal models of FASD. To determine how developmental ethanol exposure affects adult cerebellar microglia and Purkinje cells, we used a human third-trimester binge exposure model in which mice received ethanol or saline from postnatal (P) days 4-9. In adolescence, cerebellar cranial windows were implanted and mice were aged to young adulthood for examination of microglia and Purkinje cells in vivo with two-photon imaging or in fixed tissue. Ethanol had no effect on microglia density, morphology, dynamics, or injury response. However, Purkinje cell linear frequency was reduced by ethanol. Microglia-Purkinje cell interactions in the Purkinje Cell Layer were altered in females compared to males. Overall, developmental ethanol exposure had few effects on cerebellar microglia in young adulthood and Purkinje cells appeared to be more susceptible to its effects.

Constitutional chromosomal anomalies in children, fetal alcohol syndrome, and maternal toxicant exposures: A longitudinal cohort study.

DNA alterations in gametes, which may occur either spontaneously or as a result of exposure to genotoxicants, can lead to constitutional chromosomal anomalies in the offspring. Alcohol is an established genotoxicant. The goal of this hypothesis-testing longitudinal cohort study was to evaluate the effect of significant/sustained maternal alcohol exposure on clinically diagnosed constitutional chromosomal anomalies among children diagnosed with fetal alcohol syndrome (FAS). De-identified eligibility and claim healthcare records, prospectively generated from the 1990-2012 Florida Medicaid system within the Independent Healthcare Research Database (IHRD), were analyzed. Children examined were continuously eligible with ≥ 8 outpatient office visits during the 96-month period following birth. Among these children, 377 were diagnosed with FAS and 137,135 were not. The incidence rate of chromosomal anomalies involving segregation (trisomy 13, 18, or 21, n = 625), microdeletions (microdeletion syndromes, n = 39), and point mutations (sickle-cell anemia/cystic fibrosis, n = 2570) were examined using frequency risk ratio (RR) and logistic regression (adjusted odds ratio (aOR) for sex, race, residence, socioeconomic/environmental exposure status, and birth date) models. The incidence rates of chromosomal anomalies involving segregation (RR=5.92, aOR=5.85) and microdeletions (RR=41.6, aOR=34.1) were significantly increased in the FAS cohort as compared to the non-diagnosed cohort, but there was no difference in the incidence rate of point mutations (RR=1.14, aOR=1.29). Maternal toxicant exposure should be considered in the etiology of constitutional chromosomal anomaly in offspring.

Racial and ethnic disparities in psychological care for individuals with FASD: a dis/ability studies and critical race theory perspective toward improving prevention, assessment/diagnosis, and intervention.

Fetal alcohol spectrum disorders (FASD) are among the most common neurodevelopmental disorders and substantially impact public health. FASD can affect people of all races and ethnicities; however, there are important racial and ethnic disparities in alcohol-exposed pregnancy prevention, assessment and diagnosis of FASD, and interventions to support individuals with FASD and their families. In this article we use the Dis/Ability Studies and Critical Race Theory (Dis/Crit) framework to structure the exploration of disparities and possible solutions within these three areas (prevention, diagnosis, intervention). Dis/Crit provides a guide to understanding the intersection of dis/ability and race, while framing both as social constructs. Following the Dis/Crit framework, the systemic, historical, and contemporary racism and ableism present in psychological care is further discussed. We aim to elucidate these racial and ethnic disparities within the fields of psychology and neuropsychology through the Dis/Crit framework and provide potential points of action to reduce these disparities.

Low to moderate prenatal alcohol exposure and neurodevelopment in a prospective cohort of early school aged children.

Evidence is strong for adverse fetal effects of high level or chronic prenatal alcohol exposure (PAE), but many pregnant women continue to drink at lower levels. The 'Asking Questions about Alcohol in pregnancy' prospective cohort aimed to determine the neurodevelopmental consequences at 6-8 years of age of low to moderate PAE. 1570 women from seven public antenatal clinics in Melbourne, Australia, provided information on frequency and quantity of alcohol use, and obstetric, lifestyle and socio-environmental confounders at four gestation timepoints. PAE was classified into five trajectories plus controls. At 6-8 years, 802 of 1342 eligible families took part and completed a questionnaire (60%) and 696 children completed neuropsychological assessments (52%). Multiple linear regressions examined mean outcome differences between groups using complete case and multiple imputation models. No meaningful relationships were found between any of the PAE trajectories and general cognition, academic skills, motor functioning, behaviour, social skills, social communication, and executive function. Maternal education most strongly influenced general cognition and academic skills. Parenting behaviours and financial situation were associated with academic skills, behaviour, social skills and/or executive function. The lack of association between PAE and neurodevelopment at 6-8 years may partly be explained by cumulative positive effects of socio-environmental factors.

Sex-specific Differences in Resting Oscillatory Dynamics in Children with Prenatal Alcohol Exposure.

At rest children with prenatal alcohol exposure (PAE) exhibit impaired static and dynamic functional connectivity, along with decreased alpha oscillations. Sex-specific information regarding the impact of PAE on whole-brain resting-state gamma spectral power remains unknown. Eyes-closed and eyes-open MEG resting-state data were examined in 83 children, ages 6-13 years of age. Using a matched design, the sample consisted of 42 typically developing children (TDC) (22 males/20 females) and 41 children with PAE and/or a fetal alcohol spectrum disorders (FASD) diagnosis (21 males/20 females). Whole-brain source resting-state spectral power was examined to determine group and sex specific relationships. Within gamma, we found sex and group specific changes such that female participants with PAE/FASD had increased gamma power when compared to female TDC and male participants with PAE/FASD. These differences were detected in most source regions analyzed during both resting-states, and were observed across the age spectrum examined. Within delta, we found sex and group specific changes such that female participants with PAE/FASD had decreased delta power when compared to female TDC and male participants with PAE/FASD. The reduced delta oscillations in female participants with PAE/FASD were detected in several source regions during eyes-closed rest and were evident at younger ages. These results indicate PAE alters neural oscillations during rest in a sex-specific manner, with females with PAE/FASD showing the largest perturbations. These results further demonstrate PAE has global effects on resting-state spectral power and connectivity, creating long-term consequences by potentially disrupting the excitation/inhibition balance in the brain, interrupting normative neurodevelopment.

Optogenetic stimulation of corticostriatal circuits improves behavioral flexibility in mice with prenatal alcohol exposure.

Fetal alcohol spectrum disorder (FASD) is the most common preventable form of developmental and neurobehavioral disability. Animal models have demonstrated that even low to moderate prenatal alcohol exposure (PAE) is sufficient to impair behavioral flexibility in multiple domains. Previously, utilizing a moderate limited access drinking in the dark paradigm, we have shown that PAE 1) impairs touchscreen pairwise visual reversal in male adult offspring 2) leads to small but significant decreases in orbitofrontal (OFC) firing rates 3) significantly increases dorsal striatum (dS) activity and 4) aberrantly sustains OFC-dS synchrony across early reversal. In the current study, we examined whether optogenetic stimulation of OFC-dS projection neurons would be sufficient to rescue the behavioral inflexibility induced by PAE in male C57BL/6J mice. Following discrimination learning, we targeted OFC-dS projections using a retrograde adeno-associated virus (AAV) delivered to the dS which expressed channel rhodopsin (ChR2). During the first four sessions of reversal learning, we delivered high frequency optogenetic stimulation to the OFC via optic fibers immediately following correct choice responses. Our results show that optogenetic stimulation significantly reduced the number of sessions, incorrect responses, and correction errors required to move past the early perseverative phase for both PAE and control mice. In addition, OFC-dS stimulation during early reversal learning reduced the increased sessions, correct and incorrect responding seen in PAE mice during the later learning phase of reversal but did not significantly alter later performance in control ChR2 mice. Taken together these results suggest that stimulation of OFC-dS projections can improve early reversal learning in PAE and control mice, and these improvements can persist even into later stages of the task days later. These studies provide an important foundation for future clinical approaches to improve executive control in those with FASD. This article is part of the Special Issue on "PFC circuit function in psychiatric disease and relevant models".

Quantifying alcohol-attributable disability-adjusted life years to others than the drinker in Aotearoa/New Zealand: A modelling study based on administrative data.

BACKGROUND AND AIMS: Quantifying the health burden of alcohol has largely focused upon harm to drinkers, which is an underestimate. There is a growing literature on alcohol's harm to others (HTO), but it lacks the systematic transfer of HTO into a comparative risk assessment framework. This study calculated disability-adjusted life years (DALYs) for fetal alcohol spectrum disorder (FASD), interpersonal violence and traffic injury due to another's drinking. DESIGN: This study is a disease burden analysis, using modelling of DALYs for New Zealand in 2018. SETTING AND PARTICIPANTS: The study took place among the Aotearoa/New Zealand population in 2018. MEASUREMENTS: The involvement of others' drinking was obtained from prevalence, alcohol-attributable fraction studies and administrative data. Disability weights (DW) for FASD were adapted from fetal alcohol syndrome (FAS) weights using a Beta-Pert probability distribution; for interpersonal injury, DWs used hospital events linked with injury compensation; for traffic injury, DWs used hospital events. Populations were stratified by ethnicity, age group and gender. A descriptive comparison was made with a previous estimate of DALYs for drinkers. FINDINGS: In 2018, 78 277 healthy life years were lost in Aotearoa/New Zealand due to alcohol's HTO. The main contributor (90.3%) was FASD, then traffic crashes (6.3%) and interpersonal violence (3.4%). The indigenous population, Maori, was impacted at a higher rate (DALYs among Maori were 25 per 1000 population; among non-Maori 15 per 1000 population). The burden of HTO was greater than that to drinkers (DALYs HTO = 78 277; DALYs drinkers = 60 174). CONCLUSIONS: Disability from fetal alcohol spectrum disorder (FASD) appears to be a major contributor to alcohol's harm to others in Aotearoa/New Zealand. Taking FASD into account, the health burden of harm to others is larger than harm to the drinker in Aotearoa/New Zealand, and ethnicity differences show inequity in harm to others. Quantification of the burden of harm informs the value of implementing effective alcohol policies and should include the full range of harms.

Developmental alcohol exposure is exhausting: Sleep and the enduring consequences of alcohol exposure during development.

Prenatal alcohol exposure is the leading nongenetic cause of human intellectual impairment. The long-term impacts of prenatal alcohol exposure on health and well-being are diverse, including neuropathology leading to behavioral, cognitive, and emotional impairments. Additionally negative effects also occur on the physiological level, such as the endocrine, cardiovascular, and immune systems. Among these diverse impacts is sleep disruption. In this review, we describe how prenatal alcohol exposure affects sleep, and potential mechanisms of those effects. Furthermore, we outline the evidence that sleep disruption across the lifespan may be a mediator of some cognitive and behavioral impacts of developmental alcohol exposure, and thus may represent a promising target for treatment.

Modeling Fetal Alcohol Spectrum Disorders in Zebrafish to Characterize the Impact of an Adverse Embryonic Environment on Adult Social Behavior.

Fetal alcohol spectrum disorders (FASD) describe all alcohol-induced birth defects. Birth defects such as growth deficiencies, craniofacial, behavioral, and cognitive abnormalities are associated with FASD. Social difficulties are common behavioral abnormalities associated with FASD and often result in serious health issues. Animal models are critical to understanding the mechanisms responsible for ethanol-induced social defects. Zebrafish are social vertebrates that produce externally fertilized transparent eggs; these characteristics provide researchers with a precise yet simple procedure for creating the FASD phenotype and an innate behavior that can be leveraged to model the social deficits associated with FASD. Thus, zebrafish are ideal for characterizing the social deficits of FASD. The goal of the current protocol is to provide the user with a simple behavioral assay that can be used to characterize the consequences of a negative environment early during development and the effects it can have on social behavior in adulthood. The protocol can be used to characterize the effect mutations or teratogens have on adult social behavior. The protocol outlined here demonstrates how to characterize the social behavior of individual fish during a 20-min social assay. Furthermore, the data obtained using the current protocol provides evidence that the protocol can be used to characterize the effects of embryonic ethanol-induced social defects in adult zebrafish.

Scoping review on the role of the family doctor in the prevention and care of patients with foetal alcohol spectrum disorder.

BACKGROUND: Foetal alcohol spectrum disorder (FASD) is the leading preventable cause of nongenetic mental disability. Given the patient care pathway, the General Practitioner (GP) is in the front line of prevention and identification of FASD. Acknowledging the importance of the prevalence of FASD, general practitioners are in the front line both for the detection and diagnosis of FASD and for the message of prevention to women of childbearing age as well as for the follow-up. OBJECTIVES: The main objective of the scoping review was to propose a reference for interventions that can be implemented by a GP with women of childbearing age, their partners and patients with FASD. The final aim of this review is to contribute to the improvement of knowledge and quality of care of patients with FASD. METHODS: A scoping review was performed using databases of peer-reviewed articles following PRISMA guidelines. The search strategy was based on the selection and consultation of articles on five digital resources. The advanced search of these publications was established using the keywords for different variations of FASD: "fetal alcohol syndrome," "fetal alcohol spectrum disorder," "general medicine," "primary care," "primary care"; searched in French and English. RESULTS: Twenty-three articles meeting the search criteria were selected. The interventions of GPs in the management of patients with FASD are multiple: prevention, identification, diagnosis, follow-up, education, and the role of coordinator for patients, their families, and pregnant women and their partners. FASD seems still underdiagnosed. CONCLUSION: The interventions of GPs in the management of patients with FASD are comprehensive: prevention, identification, diagnosis, follow-up, education, and the role of coordinator for patients, their families, and pregnant women and their partners. Prevention interventions would decrease the incidence of FASD, thereby reducing the incidence of mental retardation, developmental delays, and social, educational and legal issues. A further study with a cluster randomized trial with a group of primary care practitioners trained in screening for alcohol use during pregnancy would be useful to measure the impact of training on the alcohol use of women of childbearing age and on the clinical status of their children.

Polymorphisms in the choline transporter SLC44A1 are associated with reduced cognitive performance in normotypic but not prenatal alcohol-exposed children.

BACKGROUND: Choline is essential for healthy cognitive development. Single nucleotide polymorphisms (SNPs; rs3199966(G), rs2771040(G)) within the choline transporter SLC44A1 increase risk for choline deficiency. In a choline intervention trial of children who experienced prenatal alcohol exposure (PAE), these alleles are associated with improved cognition. OBJECTIVE: This study aimed to determine if SNPs within SLC44A1 are differentially associated with cognition in children with PAE compared with normotypic controls (genotype × exposure). A secondary objective tested for an association of these SNPs and cognition in controls (genotype-only). DESIGN: This is a secondary analysis of data from the Collaborative Initiative on Fetal Alcohol Spectrum Disorders. Participants (163 normotypic controls, 162 PAE) underwent psychological assessments and were genotyped within SLC44A1. Choline status was not assessed. Association analysis between genotype × exposure was performed using an additive genetic model and linear regression to identify the allelic effect. The primary outcome was the interaction between SLC44A1 genotype × exposure status with respect to cognition. The secondary outcome was the cognitive-genotype association in normotypic controls. RESULTS: Genotype × exposure analysis identified 7 SNPs in SLC44A1, including rs3199966(G) and rs2771040(G), and in strong linkage (D' ≥ 0.87), that were associated (adjusted P ≤ 0.05) with reduced performance in measures of general cognition, nonverbal and quantitative reasoning, memory, and executive function (ß, 1.92-3.91). In controls, carriers of rs3199966(GT or GG) had worsened cognitive performance than rs3199966(TT) carriers (ß, 0.46-0.83; P < 0.0001), whereas cognitive performance did not differ by rs3199966 genotype in those with PAE. CONCLUSIONS: Two functional alleles that increase vulnerability to choline deficiency, rs3199966(G) (Ser644Ala) and rs2771040(G) (3' untranslated region), are associated with worsened cognition in otherwise normotypic children. These alleles were previously associated with greater cognitive improvement in children with PAE who received supplemental choline. The findings endorse that choline benefits cognitive development in normotypic children and those with PAE.

Prenatal alcohol exposure alters expression of genes involved in cell adhesion, immune response, and toxin metabolism in adolescent rat hippocampus.

Prenatal alcohol exposure (PAE) can result in mild to severe consequences for children throughout their lives, with this range of symptoms referred to as Fetal Alcohol Spectrum Disorders (FASD). These consequences are thought to be linked to changes in gene expression and transcriptional programming in the brain, but the identity of those changes, and how they persist into adolescence are unclear. In this study, we isolated RNA from the hippocampus of adolescent rats exposed to ethanol during prenatal development and compared gene expression to controls. Briefly, dams were either given free access to standard chow ad libitum (AD), pair-fed a liquid diet (PF) or were given a liquid diet with ethanol (6.7% ethanol, ET) throughout gestation (gestational day (GD) 0-20). All dams were given control diet ad libitum beginning on GD 20 and throughout parturition and lactation. Hippocampal tissue was collected from adolescent male and female offspring (postnatal day (PD) 35-36). Exposure to ethanol caused widespread downregulation of many genes as compared to control rats. Gene ontology analysis demonstrated that affected pathways included cell adhesion, toxin metabolism, and immune responses. Interestingly, these differences were not strongly affected by sex. Furthermore, these changes were consistent when comparing ethanol-exposed rats to pair-fed controls provided with a liquid diet and those fed ad libitum on a standard chow diet. We conclude from this study that changes in genetic architecture and the resulting neuronal connectivity after prenatal exposure to alcohol continue through adolescent development. Further research into the consequences of specific gene expression changes on neural and behavioral changes will be vital to our understanding of the FASD spectrum of diseases.

Strong Born-A First of Its Kind National FASD Prevention Campaign in Australia Led by the National Aboriginal Community Controlled Health Organisation (NACCHO) in Collaboration with the Aboriginal Community Controlled Health Organisations (ACCHOs).

The Strong Born Campaign (2022-2025) was launched by the National Aboriginal Community Controlled Health Organisation (NACCHO) in 2023. Strong Born is the first of its kind national Aboriginal and Torres Strait Islander health promotion campaign to address Fetal Alcohol Spectrum Disorder (FASD) within Australia. Strong Born was developed to address a longstanding, significant gap in health promotion and sector knowledge on FASD, a lifelong disability that can result from alcohol use during pregnancy. Utilizing a strengths-based and culturally sound approach, NACCHO worked closely with the Aboriginal Community Controlled Health Organisations (ACCHOs) to develop the campaign through co-design, as described in this paper. Since its inception, the ACCHOs have continually invested in driving change towards improvements in Aboriginal health determinants and health promotion. The Strong Born Campaign developed culturally safe health promotion tool kits designed for the community and health sector staff and also offered communities the opportunity to apply for FASD Communications and Engagement Grants to engage in local campaign promotion. The tool kits have been disseminated to 92 ACCHOs across Australia. This paper describes the development of the Strong Born Campaign and activities following its launch in February 2023 from an Indigenous context within Australia, as described by NACCHO.