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.

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.

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.

Vision outcomes in children with fetal alcohol spectrum disorders.

BACKGROUND: Previous studies demonstrated that children with Fetal Alcohol Spectrum Disorders (FASD) are more likely to have vision impairments. However, existing human clinical and epidemiological investigations are few and include limited sample sizes. This study aimed to explore the association between ophthalmologic abnormalities and FASD in a sample of 5-7 year old children in the general population. METHODS: This was a cross-sectional study nested in a larger study intended to estimate the prevalence of FASD in San Diego, California, conducted between 2012 and 2014. Prenatal exposure to alcohol, dysmorphology examinations, and a neurobehavioral testing battery were collected for each child and an FASD diagnosis was assigned. Parents of participating children were asked to release their child's vision screening or diagnostic records. RESULTS: Vision records were obtained for 424 participants in the larger prevalence study. Of these, 53 children were classified as having FASD. A statistically significant association was found between FASD and a diagnosis of strabismus; 5/42 (11.9%) of children who were classified as having FASD had strabismus compared to 6/290 (2.1%) of children who were not classified as having FASD (p = .01). All five cases of strabismus in the FASD group occurred in 19 children classified as having partial fetal alcohol syndrome (pFAS). No association was found between FASD and vision impairment (p = .23), refractive errors (p = .66), glasses/contact lens prescription (p = .30), or having one or more ophthalmological abnormalities (p = .97). CONCLUSIONS: An association between strabismus and FASD, specifically partial FAS, suggests that the effect of alcohol exposure on risk of strabismus must be severe enough to result in facial features consistent with FASD. This emphasizes the importance of vision screening in children with FASD.

A multi-organ analysis of the role of mTOR in fetal alcohol spectrum disorders.

Alcohol exposure during gestation can lead to fetal alcohol spectrum disorders (FASD), an array of cognitive and physical developmental impairments. Over the past two and a half decades, Mammalian Target of Rapamycin (mTOR) has emerged at the nexus of many fields of study, and has recently been implicated in FASD etiology. mTOR plays an integral role in modulating anabolic and catabolic activities, including protein synthesis and autophagy. These processes are vital for proper development and can have long lasting effects following alcohol exposure, such as impaired hippocampal and synapse formation, reduced brain size, as well as cognitive, behavioral, and memory impairments. We highlight recent advances in the field of FASD, primarily with regard to animal model discoveries and discuss the interaction between alcohol and mTOR in the context of various tissues, including brain, placenta, bone, and muscle, with respect to developmental alcohol exposure paradigms. The current review focuses on novel FASD research within the context of the mTOR signaling and sheds light on mechanistic etiologies at various biological levels including molecular, cellular, and functional, across multiple stages of development and illuminates the dichotomy between the different mTOR complexes and their unique signaling roles.

Synaptic Plasticity Abnormalities in Fetal Alcohol Spectrum Disorders.

The brain's ability to strengthen or weaken synaptic connections is often termed synaptic plasticity. It has been shown to function in brain remodeling following different types of brain damage (e.g., drugs of abuse, alcohol use disorders, neurodegenerative diseases, and inflammatory conditions). Although synaptic plasticity mechanisms have been extensively studied, how neural plasticity can influence neurobehavioral abnormalities in alcohol use disorders (AUDs) is far from being completely understood. Alcohol use during pregnancy and its harmful effects on the developing offspring are major public health, social, and economic challenges. The significant attribute of prenatal alcohol exposure on offspring is damage to the central nervous system (CNS), causing a range of synaptic structural, functional, and behavioral impairments, collectively called fetal alcohol spectrum disorder (FASD). Although the synaptic mechanisms in FASD are limited, emerging evidence suggests that FASD pathogenesis involves altering a set of molecules involved in neurotransmission, myelination, and neuroinflammation. These studies identify several immediate and long-lasting changes using many molecular approaches that are essential for synaptic plasticity and cognitive function. Therefore, they can offer potential synaptic targets for the many neurobehavioral abnormalities observed in FASD. In this review, we discuss the substantial research progress in different aspects of synaptic and molecular changes that can shed light on the mechanism of synaptic dysfunction in FASD. Increasing our understanding of the synaptic changes in FASD will significantly advance our knowledge and could provide a basis for finding novel therapeutic targets and innovative treatment strategies.

Impact of alcohol exposure on neural development and network formation in human cortical organoids.

Prenatal alcohol exposure is the foremost preventable etiology of intellectual disability and leads to a collection of diagnoses known as Fetal Alcohol Spectrum Disorders (FASD). Alcohol (EtOH) impacts diverse neural cell types and activity, but the precise functional pathophysiological effects on the human fetal cerebral cortex are unclear. Here, we used human cortical organoids to study the effects of EtOH on neurogenesis and validated our findings in primary human fetal neurons. EtOH exposure produced temporally dependent cellular effects on proliferation, cell cycle, and apoptosis. In addition, we identified EtOH-induced alterations in post-translational histone modifications and chromatin accessibility, leading to impairment of cAMP and calcium signaling, glutamatergic synaptic development, and astrocytic function. Proteomic spatial profiling of cortical organoids showed region-specific, EtOH-induced alterations linked to changes in cytoskeleton, gliogenesis, and impaired synaptogenesis. Finally, multi-electrode array electrophysiology recordings confirmed the deleterious impact of EtOH on neural network formation and activity in cortical organoids, which was validated in primary human fetal tissues. Our findings demonstrate progress in defining the human molecular and cellular phenotypic signatures of prenatal alcohol exposure on functional neurodevelopment, increasing our knowledge for potential therapeutic interventions targeting FASD symptoms.

The prevalence of fetal alcohol spectrum disorders in rural communities in South Africa: A third regional sample of child characteristics and maternal risk factors.

BACKGROUND: This study is the ninth cross-sectional community study of fetal alcohol spectrum disorders (FASD) conducted by the multidisciplinary Fetal Alcohol Syndrome Epidemiology Research team in the Western Cape Province of South Africa. It is the third comprehensive study of FASD in a rural, agricultural region of South Africa. METHODS: Population-based, active case ascertainment methods were employed among a school-based cohort to assess child physical and neurobehavioral traits, and maternal risk factor interviews were conducted to identify all children with FASD to determine its prevalence. RESULTS: Consent was obtained for 76.7% of 1158 children attending first grade in the region's public schools. Case-control results are presented for 95 with fetal alcohol syndrome (FAS), 64 with partial fetal alcohol syndrome (PFAS), 77 with alcohol-related neurodevelopmental disorder (ARND), 2 with alcohol-related birth defects (ARBD), and 213 randomly-selected controls. Four techniques estimating FASD prevalence from in-person examinations and testing yielded a range of total FASD prevalence of 206-366 per 1000. The final weighted, estimated prevalence of FAS was 104.5 per 1000, PFAS was 77.7 per 1000, ARND was 125.2 per 1000, and total FASD prevalence was 310 per 1000 (95% CI = 283.4-336.7). Expressed as a percentage, 31% had FASD. Although the rate of total FASD remained steady over 9 years, the proportion of children within the FASD group has changed significantly: FAS trended down and ARND trended up. A detailed evaluation is presented of the specific child physical and neurobehavioral traits integral to assessing the full continuum of FASD. The diagnosis of a child with FASD was significantly associated with maternal proximal risk factors such as: co-morbid prenatal use of alcohol and tobacco (OR = 19.1); maternal drinking of two (OR = 5.9), three (OR = 5.9), four (OR = 38.3), or more alcoholic drinks per drinking day; and drinking in the first trimester (OR = 8.4), first and second trimesters (OR = 17.7), or throughout pregnancy (OR = 18.6). Distal maternal risk factors included the following: slight or small physical status (height, weight, and head circumference), lower BMI, less formal education, late recognition of pregnancy, and higher gravidity, parity, and older age during the index pregnancy. CONCLUSION: The prevalence of FASD remained a significant problem in this region, but the severity of physical traits and anomalies within the continuum of FASD is trending downwards.

The effects of gestational choline supplementation on cerebellar Purkinje cell number in the sheep model of binge alcohol exposure during the first trimester-equivalent.

Individuals with fetal alcohol spectrum disorders (FASD) incur enduring brain damage and neurodevelopmental impairments from prenatal alcohol exposure (PAE). Preclinical rodent models have demonstrated that choline supplementation during development can reduce the severity of adverse neurodevelopmental consequences of PAE. This study used the sheep model to evaluate dietary choline supplementation during pregnancy as a therapeutic intervention, testing the hypothesis that choline can ameliorate alcohol-induced cerebellar Purkinje cell loss. Pregnant ewes were randomly assigned either to a normal control [NC] group (n = 8), or to groups given intravenous infusions of alcohol (or saline) from gestational days 4-41 (the first trimester-equivalent). A weekly binge-drinking pattern was modeled, with three consecutive days of infusions of saline [SAL], 1.75 g/kg/day alcohol [1.75ALC], or 2.5 g/kg/day alcohol [2.5ALC] followed by four days off. Infused ewes were randomly assigned to receive dietary supplements throughout pregnancy of choline (10 mg/kg/day) or placebo (n = 8 per group). Mean blood alcohol concentrations (BAC) were significantly higher in the 2.5ALC groups (287 mg/dL) than the 1.75ALC groups (197 mg/dL). Lamb cerebella were harvested on postnatal day 180 and processed for stereological counts of Purkinje cells. Both alcohol doses caused significant reductions in Purkinje number relative to NC and SAL-Placebo groups, confirming previous findings. Effects of choline supplementation depended on infusion group: it significantly protected against Purkinje cell loss in the 2.5ALC group, had no effect in the 1.75ALC group, and significantly reduced numbers in the SAL-Choline group (though neither the SAL-Choline nor the SAL-Placebo group differed from the NC group). The protection by choline evident only in the 2.5ALC group suggests that multiple, BAC-dependent mechanisms of cerebellar damage may be activated with alcohol exposure in the first trimester, and that choline may protect against pathogenic mechanisms that emerge at higher BACs. These outcomes extend the evidence that early choline supplementation can mitigate some neurodevelopmental defects resulting from binge-like PAE.

Modulatory role of prenatal alcohol exposure and adolescent stress on the response to arthritis challenge in adult female rats.

BACKGROUND: There are known environmental risk factors associated with rheumatoid arthritis; however, less is known regarding how the prenatal environment impacts later-life risk for rheumatoid arthritis. Based on preliminary clinical data suggesting that individuals with fetal alcohol spectrum disorder (FASD) are at higher risk for autoimmune disorders, this study investigated the modulatory impact of prenatal alcohol exposure (PAE) on the inflammatory disease profile in an adjuvant-induced arthritis rat model. METHODS: Pregnant rats received liquid ethanol or control diet throughout gestation. To model the increased exposure to stressors often experienced by individuals with FASD, adolescent offspring were exposed to chronic mild stress (CMS) or remained undisturbed. In adulthood, experimental arthritis was initiated and rats terminated either at the peak or following resolution from inflammation to assess endocrine, immune, and histopathological outcomes. FINDINGS: PAE rats had an increased incidence and severity of, and impaired recovery from, arthritis. Increased joint damage was observed in PAE animals, even in the face of apparent recovery from the clinical signs of arthritis, while it appeared that oestradiol may have a protective role. Moreover, with the combination of PAE and adolescent stress, increased macrophage density was detected in the synovium of PAE but not control rats. INTERPRETATION: These findings demonstrate that PAE alters the severity and course of arthritis, highlighting the potential immunomodulatory impact of adverse prenatal exposures. In particular, these data have implications for understanding preliminary data that suggest a heightened propensity for autoimmune disorders in individuals with FASD. FUNDING: This work was supported by: National Institutes of Health/National Institute on Alcohol Abuse and Alcoholism [R37 AA007789] and Kids Brain Health Network (KBHN; Canadian Networks of Centres of Excellence) to JW, a Natural Sciences and Engineering Research Council of Canada (NSERC) CGS-D to TSB and NIH/NIAAA R01 AA022460 to JW and TSB.

Effects of nutrition and gestational alcohol consumption on fetal growth and development.

Fetal alcohol exposure can lead to a range of developmental disorders, including impaired fetal growth and development of multiple organ systems. These disorders are grouped under the term fetal alcohol spectrum disorders (FASDs). Adequate nutrition and a conducive intrauterine environment are essential for healthy fetal development. Nutrient deficiencies resulting from inadequate maternal nutrient ingestion may be compounded by alcohol-induced altered nutrient metabolism, placental clearance, and malabsorption. Alcohol-induced alteration of the intrauterine environment is the main source of developmental deficits and nutritional insufficiencies can worsen the effects on fetal development. In this review, we discuss studies examining the collective and interactive effects of nutrition (specifically iron, selenium, vitamin A, thiamine, zinc, folate, vitamin B12, choline, and amino acids) relative to gestational alcohol consumption and its effects on fetal growth and development. We also summarize scientific reports that tested potential benefits of micronutrient supplementation in animal models of fetal alcohol spectrum disorders and in humans. In summary, the deleterious effects of alcohol exposure in relation to nutrient homeostasis further validate that avoidance of alcohol consumption during pregnancy is the most effective way to mitigate the teratogenic effects of alcohol.

Transgenerational Abnormalities Induced by Paternal Preconceptual Alcohol Drinking: Findings from Humans and Animal Models.

Alcohol consumption during pregnancy and lactation is a widespread preventable cause of neurodevelopmental impairment in newborns. While the harmful effects of gestational alcohol use have been well documented, only recently, the role of paternal preconceptual alcohol consumption (PPAC) prior to copulating has drawn specific epigenetic considerations. Data from human and animal models have demonstrated that PPAC may affect sperm function, eliciting oxidative stress. In newborns, PPAC may induce changes in behavior, cognitive functions, and emotional responses. Furthermore, PPAC may elicit neurobiological disruptions, visuospatial impairments, hyperactivity disorders, motor skill disruptions, hearing loss, endocrine, and immune alterations, reduced physical growth, placental disruptions, and metabolic alterations. Neurobiological studies on PPAC have also disclosed changes in brain function and structure by disrupting the growth factors pathways. In particular, as shown in animal model studies, PPAC alters brain nerve growth factor (NGF) and brainderived neurotrophic factor (BDNF) synthesis and release. This review shows that the crucial topic of lifelong disabilities induced by PPAC and/or gestational alcohol drinking is quite challenging at the individual, societal, and familial levels. Since a nontoxic drinking behavior before pregnancy (for both men and women), during pregnancy, and lactation cannot be established, the only suggestion for couples planning pregnancies is to completely avoid the consumption of alcoholic beverages.

Maternal background alters the penetrance of growth phenotypes and sex-specific placental adaptation of offspring sired by alcohol-exposed males.

Epigenetic mechanisms of paternal inheritance are an emerging area of interest in our efforts to understand fetal alcohol spectrum disorders. In rodent models examining maternal alcohol exposures, different maternal genetic backgrounds protect or sensitize offspring to alcohol-induced teratogenesis. However, whether maternal background can mitigate sperm-inherited alterations in developmental programming and modify the penetrance of growth defects induced by preconception paternal alcohol exposures remains unaddressed. In our previous studies examining pure C57Bl/6J crosses, the offspring of alcohol-exposed sires exhibited fetal growth restriction, enlarged placentas, and decreased placental efficiency. Here, we find that in contrast to our previous studies, the F1 offspring of alcohol-exposed C57Bl/6J sires and CD-1 dams do not exhibit fetal growth restriction, with male fetuses developing smaller placentas and increased placental efficiencies. However, in these hybrid offspring, preconception paternal alcohol exposure induces sex-specific changes in placental morphology. Specifically, the female offspring of alcohol-exposed sires displayed structural changes in the junctional and labyrinth zones, along with increased placental glycogen content. These changes in placental organization are accompanied by female-specific alterations in the expression of imprinted genes Cdkn1c and H19. Although male placentae do not display overt changes in placental histology, using RNA-sequencing, we identified programmed alterations in genes regulating oxidative phosphorylation, mitochondrial function, and Sirtuin signaling. Collectively, our data reveal that preconception paternal alcohol exposure transmits a stressor to developing offspring, that males and females exhibit distinct patterns of placental adaptation, and that maternal genetic background can modulate the effects of paternal alcohol exposure.

Sex-specific effect of prenatal alcohol exposure on N-methyl-D-aspartate receptor function in orbitofrontal cortex pyramidal neurons of mice.

BACKGROUND: Alcohol consumption during pregnancy can produce behavioral and cognitive deficits that persist into adulthood. These include impairments in executive functions, learning, planning, and cognitive flexibility. We have previously shown that moderate prenatal alcohol exposure (PAE) significantly impairs reversal learning, a measure of flexibility mediated across species by different brain areas that include the orbital frontal cortex (OFC). Reversal learning is likewise impaired by genetic or pharmacological inactivation of GluN2B subunit-containing N-methyl-D-aspartate receptors (NMDARs). In the current study, we tested the hypothesis that moderate PAE persistently alters the number and function of GluN2B subunit-containing NMDARs in OFC pyramidal neurons of adult mice. METHODS: We used a rodent model of fetal alcohol spectrum disorders and left offspring undisturbed until adulthood. Using whole-cell, patch-clamp recordings, we assessed NMDAR function in slices from 90- to 100-day-old male and female PAE and control mice. Pharmacologically isolated NMDA receptor-mediated evoked excitatory postsynaptic currents (NMDA-eEPSCs) were recorded in the absence and presence of the GluN2B antagonist, Ro25-6981(1 µM). In a subset of littermates, we evaluated the level of GluN2B protein expression in the synaptic fraction using Western blotting technique. RESULTS: Our results indicate that PAE females show significantly larger (~23%) NMDA-eEPSC amplitudes than controls, while PAE induced a significant decrease (~17%) in NMDA-eEPSC current density of pyramidal neurons recorded in slices from male mice. NMDA-eEPSC decay time was not affected in PAE-exposed mice from either sex. The contribution of GluN2B subunit-containing NMDARs to the eEPSCs was not significantly altered by PAE. Moreover, there were no significant changes in protein expression in the synaptic fraction of either PAE males or females. CONCLUSIONS: These findings suggest that low-to-moderate PAE modulates NMDAR function in pyramidal neurons in a sex-specific manner, although we did not find evidence that the effect is mediated by dysfunction of synaptic GluN2B subunit-containing NMDARs.

Maternal psycho-social risk factors associated with maternal alcohol consumption and Fetal Alcohol Spectrum Disorder: a systematic review.

PURPOSE: Fetal Alcohol Spectrum Disorder (FASD) is a preventable range of neurocognitive disorders associated with the biological mother's consumption of alcohol during pregnancy. However, on average, 45% of Australian women continue to consume alcohol during pregnancy resulting in a high rate of alcohol-exposed pregnancies and risk of FASD. This level of exposure is higher than the estimated global average of alcohol-exposed pregnancies (9.8%). This systematic literature review aims to identify demographic, health and psycho-social variables associated with alcohol consumption during pregnancy which may lead to FASD. METHODS: Using PRISMA principles, this systematic literature review reports on psycho-social factors which increase the risk of alcohol consumption during pregnancy thereby increasing the risk of FASD. RESULTS: Fourteen studies were accepted into this review. Studies were conducted across several countries and included a total of 386,067 cases. Seven studies were case-controlled and seven were cross-sectional design. Multiple studies identified the significance of prior mental illness, anxiety, depression, exposure to abuse and/or domestic violence and alcohol consumption behaviours of partners and family members as strong predictors of risky alcohol consumption during pregnancy and therefore associated risk of FASD. CONCLUSION: Clinical services may be able to use the evidence-based findings from this review to improve assessment and treatment services for vulnerable women to reduce alcohol-exposed pregnancies.

Effects of prenatal alcohol exposure on cognitive and behavioral development: Findings from a hierarchical meta-analysis of data from six prospective longitudinal U.S. cohorts.

BACKGROUND: Cognitive and behavioral sequelae of prenatal alcohol exposure (PAE) continue to be prevalent in the United States and worldwide. Because these sequelae are also common in other neurodevelopmental disorders, researchers have attempted to identify a distinct neurobehavioral profile to facilitate the differential diagnosis of fetal alcohol spectrum disorders (FASD). We used an innovative, individual participant meta-analytic technique to combine data from six large U.S. longitudinal cohorts to provide a more comprehensive and reliable characterization of the neurobehavioral deficits seen in FASD than can be obtained from smaller samples. METHODS: Meta-analyses were performed on data from 2236 participants to examine effects of PAE (measured as oz absolute alcohol/day (AA/day)) on IQ, four domains of cognition function (learning and memory, executive function, reading achievement, and math achievement), sustained attention, and behavior problems, after adjusting for potential confounders using propensity scores. RESULTS: The effect sizes for IQ and the four domains of cognitive function were strikingly similar to one another and did not differ at school age, adolescence, or young adulthood. Effect sizes were smaller in the more middle-class Seattle cohort and larger in the three cohorts that obtained more detailed and comprehensive assessments of AA/day. PAE effect sizes were somewhat weaker for parent- and teacher-reported behavior problems and not significant for sustained attention. In a meta-analysis of five aspects of executive function, the strongest effect was on set-shifting. CONCLUSIONS: The similarity in the effect sizes for the four domains of cognitive function suggests that PAE affects an underlying component or components of cognition involving learning and memory and executive function that are reflected in IQ and academic achievement scores. The weaker effects in the more middle-class cohort may reflect a more cognitively stimulating environment, a different maternal drinking pattern (lower alcohol dose/occasion), and/or better maternal prenatal nutrition. These findings identify two domains of cognition-learning/memory and set-shifting-that are particularly affected by PAE, and one, sustained attention, which is apparently spared.

[ALCOHOL DRINKING DURING PREGNANCY AND ITS EFFECTS ON THE FETUS AND THE NEWBORN].

INTRODUCTION: Alcohol consumption during pregnancy has become a prevalent phenomenon worldwide in general, as well as in Israel in particular. This habit is associated with an increase in various complications during pregnancy - mainly fetal alcohol syndrome and post-natal fetal alcohol spectrum disorder. There is no "safe limit" for alcohol consumption during pregnancy and alcohol drinking may be detrimental to the fetus or to the newborn when consumed at any stage of the pregnancy. The negative effects of alcohol consumption during pregnancy are also related to a shortage of key nutritional elements due to this habit. The main negative results of this habit are fetal alcohol syndrome and fetal alcohol spectrum disorders. Pregnant women after infertility treatment are also not deterred from drinking alcohol. Education of pregnant women is currently regarded as the best treatment.

Evaluation of the German biographic screening interview for fetal alcohol spectrum disorder (BSI-FASD).

Alcohol consumption during pregnancy may lead to permanent damage in the offspring, including fetal alcohol spectrum disorders (FASD), which have an estimated prevalence of 1-8% worldwide. In adulthood, diagnosing FASD is time-consuming and costly. This study aimed to evaluate the discriminatory power of a German screening instrument for FASD in adults-the biographic screening interview (BSI-FASD). In an open-label comparative cohort study wherein a one-time survey was administered per participant, we compared 22 subjects with confirmed FASD with control groups of 15 subjects diagnosed with attention deficit hyperactivity disorder (ADHD), 20 subjects with alcohol or opiate dependence, 18 subjects with depression, and 31 controls without prenatal alcohol exposure. The BSI-FASD was found to be resource-efficient, user-friendly, comprehensible, and easily applicable. It provided an overall good convergent and discriminant validity with a sensitivity of 0.77 (adapted 0.86) and specificities between 0.70 and 1.00. The BSI-FASD subdomains differed in their power to differentiate FASD from the groups. This study established that the BSI-FASD is an efficient instrument to screen adults with suspected FASD. The BSI-FASD may facilitate future diagnostic evaluation and thereby contribute to improved treatment of affected individuals.

Early-life exposure to alcohol and the risk of alcohol-induced liver disease in adulthood.

Alcohol consumption remains prevalent among pregnant and nursing mothers despite the well-documented adverse effects this may have on the offspring. Moderate-to-high levels of alcohol consumption in pregnancy result in fetal alcohol syndrome (FAS) disorders, with brain defects being chief among the abnormalities. Recent findings indicate that while light-to-moderate levels may not cause FAS, it may contribute to epigenetic changes that make the offspring prone to adverse health outcomes including metabolic disorders and an increased propensity in the adolescent-onset of drinking alcohol. On the one hand, prenatal alcohol exposure (PAE) causes epigenetic changes that affect lipid and glucose transcript regulating genes resulting in metabolic abnormalities. On the other hand, it can program offspring for increased alcohol intake, enhance its palatability, and increase acceptance of alcohol's flavor through associative learning, making alcohol a plausible second hit for the development of alcohol-induced liver disease. Adolescent drinking results in alcohol dependence and abuse in adulthood. Adolescent drinking results in alcohol dependence and abuse in adulthood. Alterations on the opioid system, particularly, the mu-opioid system, has been implicated in the mechanism that induces increased alcohol consumption and acceptance. This review proposes a mechanism that links PAE to the development of alcoholism and eventually to alcoholic liver disease (ALD), which results from prolonged alcohol consumption. While PAE may not lead to ALD development in childhood, there are chances that it may lead to ALD in adulthood.