Fetal Alcohol Research Articles

Association of prenatal alcohol exposure and prenatal depressive symptoms with offspring hair cortisol in childhood and adolescence.

Fetal alcohol spectrum disorder (FASD) prevalence is high in South Africa, and is a significant public health concern. The long-term consequences of FASD are devastating to the individual, their family and society. Costs associated with managing these patients and the consequences of their disorder are significant. National ownership and multisectorial involvement are required to design and implement a successful FASD prevention programme.

Perinatal and prenatal alcohol exposure impairs striatal cholinergic function and cognitive flexibility in adult offspring.

Impact of prenatal alcohol exposure in midlife: an assessment of the retina in the vervet monkey.

Ethanol exposure impaired mitotic division in apical radial glial cells and disrupted early cortical development in human forebrain organoids: Implications for ethanol-induced microcephaly.

MicroRNAs as potential biomarkers for assessing prenatal alcohol exposure: A narrative review analyzing differences between human and animal studies

Some Today, More Tomorrow: A Pilot Study on Delay Discounting in Adolescents with Fetal Alcohol Spectrum Disorder (FASD)

Intrauterine stress exposure is associated with offspring health. DNA methylation (DNAm) is a putative underlying mechanism, but large population-based studies reported limited associations between prenatal stress and DNAm. Recent research has shown that environmental factors in interaction with genetic variants are better predictors of DNAm than environment or genotype alone. We investigated whether interactions of maternal prenatal stress with genetic variants are associated with DNAm at birth. We examined 2963 mother-child pairs from the population-based Generation R Study and Avon Longitudinal Study of Parents and Children, using a harmonized, comprehensive cumulative prenatal stress measure. We tested genome-wide genotype-by-prenatal stress interactions on epigenome-wide DNAm (GxEmodel), and models including only genetic variants (Gmodel) or prenatal stress (Emodel) as predictors. Follow-up analyses included Gene Ontology analyses and mediation analyses of prenatal alcohol intake, smoking, gestational age, and birth weight. We report two independent gene-by-prenatal-stress interactions on DNAm after multiple testing correction, including five genetic variants in CHD2 and ORC5, and two DNAm sites in EPPK1. By comparison, the Gmodel showed 691,202 associations and the Emodel showed three associations in genes AHRR, GFI1, and MYO1G, which could largely be explained by prenatal smoking. Genes linked to suggestive GxEmodel results were often involved in neuronal development. Our results provide some support of interaction of prenatal stress with the child's genome on DNAm of genes related to neuronal development. Based on these models, genetic main effects on DNA methylation at birth were much more abundant than gene-by-prenatal stress interactions were.

Children with foetal alcohol spectrum disorder (FASD) present with significant sleep disturbance. This pilot trial aimed to examine the feasibility of conducting a larger randomised controlled trial (RCT) in this population and the potential effectiveness of melatonin to treat onset insomnia. Children with sleep onset delay and a designation of 'at risk' of FASD or a diagnosis of FASD were recruited to a 10-week, double-blind, placebo-controlled, crossover study of melatonin. Sleep outcomes were assessed using actigraphy. The child sleep habit questionnaire (CSHQ) and measures of executive functioning and carer stress were completed at baseline and after each treatment phase. Fifty-nine children were assessed for eligibility, 18 were ineligible as they were taking sleep medication, and eight children entered the trial. Four received melatonin for 3 weeks followed by placebo for 3 weeks (arm A) and four received placebo followed by melatonin (arm B). Processes involving data collection and retention were acceptable. However, significant issues regarding recruitment were found. Quantitative measures were appropriate with significant reductions in sleep onset latency (n = 6) in the melatonin condition relative to the placebo condition (p = 0.003), and bedtime resistance (n = 8) according to the CSHQ (p = 0.004). No serious adverse events were reported. A randomised crossover design was feasible in this population; however, recruitment should be conducted across multiple sites. Melatonin is potentially effective at reducing sleep onset latency and behaviour difficulties at bedtime in children with or 'at risk' of FASD. Australian New Zealand Clinical Trials Registry (12619001360101).

Antenatal alcohol consumption can significantly impact fetal development, leading to long-lasting effects including Fetal Alcohol Spectrum Disorder (FASD). When pregnant women or people consume alcohol, it crosses the placenta and disrupts neural development, contributing to low birth weight, microcephaly and lifelong cognitive and behavioural impairments.1 Midwives can play a critical role in addressing this issue by educating women, people and families. They can initiate open, non-judgemental discussions and coordinate compassionate multidisciplinary care. To enhance prevention, midwifery education should include alcohol related health interventions enabling midwives and students with the knowledge and skills to counsel and offer safe, quality support to those with alcohol-related problems.

The Role of DNA Methylation in Alcohol-mediated Neurodevelopmental Toxicity.

BackgroundPrenatal Alcohol Use (PAU) has detrimental effects on mothers and their children. Robust estimates of the prevalence of PAU and associated risk factors are critical for informing interventions to reduce adverse health impacts. This study aimed to estimate the prevalence and risk factors of PAU among Aboriginal and non-Aboriginal mothers in the Northern Territory of Australia.MethodsWe used linked individual-level records from the NT perinatal register, hospital admissions, and emergency department presentations to estimate the prevalence of PAU for all 19,588 births to NT-resident women from 2013 to 2017. Permutation analysis was used to create four PAU categories: no PAU, early PAU (alcohol use in early pregnancy only), continued PAU (alcohol use in early and late pregnancy), and extreme PAU (hospital admissions/ presentations for alcohol-related diagnosis during pregnancy). Multinomial logit models explored the associations between sociodemographic and clinical factors and degrees of PAU. A relative risk ratio (RRR) with a 95% confidence interval (CI) was used to measure associations.ResultsThere were 19,588 births to 16,199 women during the study period (6,310 births to 5,207 Aboriginal women). The mean gestational age at birth for Aboriginal women was 37.8 (95% CI: 37.7, 37.9) weeks and 38.7 (38.6, 38.8) weeks for non-Aboriginal women. The overall PAU prevalence for births to Aboriginal women was 13.1% (95% CI: 12.2, 14.0), including 5.9% (95% CI: 5.2, 6.5) early PAU, 4.3% (95% CI: 3.8, 4.8) continued PAU, and 2.8% (95% CI: 2.4, 3.3) “extreme” PAU. The overall prevalence for non-Aboriginal women was 2.3% (95% CI: 2.1, 2.6), including 1.7% (95% CI: 1.5, 1.9), 0.53% (95% CI: 0.4, 0.7) and 0.1% (95% CI: 0.02, 0.1) for each category, respectively. Age, smoking, and substance misuse-related hospitalisation were associated with an increased risk of PAU among both populations. Being a victim of violence was an additional risk among Aboriginal women. More than five antenatal care (ANC) visits were associated with less PAU. However, 17.9% (n = 3520) of births had missing records related to PAU.ConclusionThe study provides refined prevalence estimates for PAU across groups with increasing risk of harm. Early identification and effective engagement with women at risk of PAU are critical for improving outcomes for mothers and their children. Targeted interventions like enhanced services that support cessation of alcohol and other drugs (AOD), strengthening families, and sustained engagement with culturally safe, trauma-informed maternity care may aid in reducing PAU. The study also highlights the critical need to enhance both the quality and completeness of the routine recording of alcohol use during pregnancy.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12884-025-08216-5.

Foetal alcohol spectrum disorders (FASDs) refer to a range of adverse physical, behavioural and cognitive effects caused by perinatal alcohol exposure. While cognitive impairments are well documented, FASD has also been associated with sleep disturbances and circadian rhythm disruptions. This study aimed to examine the effects of perinatal alcohol exposure on circadian rhythms at behavioural and gene expression levels across two developmental stages (adolescence and adulthood) in both male and female mice. Using a validated prenatal and lactation alcohol exposure (PLAE) protocol, we assessed circadian patterns of locomotor activity under free-running conditions and spatial memory performance during adolescence and adulthood. Additionally, we evaluated the impact of PLAE on circadian expression of clock and non-circadian genes involved in neurotransmission across key brain regions, including the medial prefrontal cortex and hippocampus. PLAE altered circadian rhythmicity and impaired spatial memory. Gene expression analyses revealed disrupted oscillatory patterns in clock genes and in genes related to plasticity and cognition, including those from the expanded endocannabinoid system (e.g. Cnr1, Dagla, Faah) and other neurotransmitter systems (e.g. Oprm1, Slc17a8, Drd1, Gabra1). These findings underscore the impact of early alcohol exposure on biological rhythms and neurobehavioural function, highlighting circadian dysregulation as a contributing factor to FASD.

Fetal alcohol spectrum disorders (FASD) is an umbrella term used to describe physical, neuropathological, and behavioral alterations caused by prenatal alcohol exposure. Caretakers often report that children with FASD experience sleep problems. However, interventions to improve sleep have not been well-studied in this population. Interestingly, supplementation with the essential nutrient choline can attenuate many behavioral alterations associated with prenatal alcohol exposure. Moreover, choline is a precursor to acetylcholine, a neurochemical that is also involved in sleep-wake modulation. Using an animal model, this study investigated the effects of developmental alcohol exposure on sleep and examined whether postnatal choline supplementation can modulate sleep alterations associated with FASD. Sprague-Dawley rat pups received ethanol (5.25 g/kg/day, 11.9% v/v) or sham intubations from postnatal days (PD) 4-9, a period of development equivalent to the human third-trimester brain growth spurt. Subjects then received subcutaneous injections with choline chloride (100 mg/kg/day) or saline from PD 10-30. On PD 32-37, subjects were individually housed to measure sleep-wake behaviors using the PiezoSleep Adapt-A-Base System. Sleep parameters, including sleep time, bout length, and number, were recorded. Ethanol-exposed subjects, particularly females, slept less during the dark cycle. In addition, females exposed to developmental alcohol exhibited more night-to-night variability in sleep duration, consistent with findings from clinical populations. In contrast, choline supplementation increased sleep duration, particularly among males exposed to developmental alcohol. Choline specifically increased sleep bout duration in ethanol-exposed subjects during the dark cycle, suggesting that choline can modify sleep patterns among subjects exposed to prenatal alcohol. These results illustrate that alcohol exposure during late gestation may lead to sleep disturbances and suggest that postnatal choline supplementation affects sleep quality. Importantly, this nutritional intervention was administered after the alcohol insult, suggesting that nutritional supplements in children with FASD may impact sleep problems.

Background/Objectives: This article aims to investigate the multifaceted effects of alcohol on neurophysiopathological development from gestational stages through adult life and the consequent dynamic-relational challenges in individuals with Fetal Alcohol Spectrum Disorder (FASD). FASD, resulting from prenatal alcohol exposure (PAE), is characterized by a range of neurological, cognitive, behavioral, and sometimes physical impairments. This article explores how alcohol and its toxic metabolites cross the placenta, inducing direct cellular toxicity and epigenetic alterations that disrupt critical neurodevelopmental processes such as neurogenesis and brain circuit formation. Clinically, individuals with FASD exhibit diverse deficits in executive functioning, learning, memory, social skills, and sensory-motor abilities, leading to significant lifelong disabilities. A central focus is the application of the World Health Organization's International Classification of Functioning, Disability and Health (ICF) criteria to comprehensively frame these disabilities. The ICF's biopsychosocial model allows for a multidimensional assessment of impairments in body functions and structures, limitations in activities, and restrictions in participation, while also considering the crucial role of environmental factors. Methods: PubMed and Semantic Scholar databases were searched for relevant papers published in English. Results: This article highlights the utility of the ICF in creating individualized functioning profiles to guide interventions and support services, addressing the limitations of traditional assessment methods. Conclusions: While the ICF framework offers a robust approach for understanding and managing FASD, further research is essential to develop and validate FASD-specific ICF-based assessment tools to enhance support and social participation for affected individuals.

Background/objectives: Alcohol use during pregnancy can result in adverse outcomes for the offspring, including Fetal Alcohol Spectrum Disorders (FASD). Psychosocial and contextual factors may influence gestational alcohol intake and women's risk perception. This systematic review aimed to assess pregnant women's and women of childbearing age's perceived risk of alcohol use during pregnancy and to evaluate their knowledge of its potential effects on children. Methods: Following the PRISMA guidelines, a systematic search was conducted in Web of Science, PubMed and PsycArticles databases for studies published up to May 2025. Eligible studies examined gestational alcohol use, risk perception, or knowledge of fetal consequences among pregnant women or women of reproductive age. Methodological quality was assessed with the Critical Appraisal of Qualitative Studies tool from the Centre for Evidence-Based Medicine (CEBM). Results: Twenty-nine studies were included. Reported prevalence of alcohol consumption during pregnancy varied considerably across settings. A substantial proportion of women perceived alcohol use during pregnancy as acceptable, often depending on quantity, frequency, type of beverage, or stage of gestation. Knowledge of FASDs was generally limited and frequently restricted to physical malformations. Misconceptions were more common among women with prior alcohol use. The findings highlight persistent gaps in risk perception and knowledge about FASDs. Conclusions: Prevention strategies should not be limited to pregnant women but should also target women of childbearing age, especially those with active drinking patterns, as well as their immediate sociocultural environment. Strengthening professional training, community-based interventions, and consistent public health messaging are essential to reduce gestational alcohol exposure.

Fetal alcohol spectrum disorders (FASD) describe a spectrum of ethanol-induced developmental defects. Ethanol susceptibility is modulated by genetics, but the underlying mechanisms remain poorly understood. In all vertebrates, complex cellular events give rise to the body plan, including gastrulation and morphogenesis of the endoderm and cranial neural crest (CNC-gives rise to the facial skeleton). These events are crucial for establishing complex signaling interactions that drive embryo development, including the formation of the facial skeleton. In zebrafish, gastrulation occurs between 6 and 10 h postfertilization (hpf), while endoderm/CNC morphogenesis occurs between 10 and 24 hpf. In previous work, planar cell polarity (PCP) mutants are ethanol-sensitive from 6 to 24 hpf (covering both gastrulation and endoderm/CNC morphogenesis), exhibiting multiple defects in the forming head. This raises the question of whether ethanol during both these time windows drives PCP-ethanol defects. We hypothesize that PCP mutants are ethanol-sensitive from 10 to 24 hpf, after gastrulation. We also hypothesize that bone morphogenetic protein (BMP) signaling (ethanol-sensitive 10-18 hpf) interacts with and sensitizes the PCP pathway to ethanol. We treated PCP/BMP mutants with ethanol over various time windows between 6 and 30 hpf and combined morphometric and linear measurements to examine facial development. We show that PCP mutants are largely ethanol-sensitive from 10 to 24 hpf. We also show that BMP mutants sensitize PCP mutants to ethanol and lead to novel ethanol-independent midline craniofacial defects. Our results suggest that the ethanol-sensitive role of the PCP pathway occurs after gastrulation, during endoderm/CNC morphogenesis, and that the PCP and BMP pathways genetically interact during the morphogenetic events. Ultimately, our work builds on a mechanistic paradigm of ethanol-induced birth defects we have been developing, connecting the conceptual framework with concrete cellular events that could be ethanol-sensitive beyond facial development.

Prenatal alcohol exposure promotes nerve injury-induced pathological pain following morphine treatment via NLRP3-mediated peripheral and central proinflammatory immune actions.

Sleep disturbance in children with prenatal alcohol exposure: a systematic review and meta-analysis.

Abstract: Background: Fetal alcohol spectrum disorders (FASD) and attention-deficit/hyperactivity disorder (ADHD) present overlapping cognitive and behavioral characteristics, leading to challenges in differential diagnosis. Existing literature indicates a high rate of comorbidity but also points to distinct neurodevelopmental profiles. Methods: We comprehensively review the current literature to delineate the similarities and differences between FASD and ADHD. Specifically, we focus on studies that investigate the cognitive and behavioral measures commonly utilized in the diagnostic processes of these conditions. In addition, we present a case study to illustrate how these similarities and differences are reflected in clinical assessment and diagnosis. Results: The literature review highlights overlapping symptoms such as impulsivity and inattention, while identifying unique markers, particularly in executive functioning, adaptive behavior, and prenatal history. The case study demonstrates how these features complicate clinical decision-making, especially in the absence of confirmed prenatal alcohol exposure. Discussion: The findings underscore the diagnostic complexity posed by the overlap of FASD and ADHD symptoms. We consider it essential to address these challenges for accurate diagnosis and developing targeted, effective intervention strategies.