Fetal Alcohol Spectrum Disorders Children Research Articles

Reduced Interhemispheric Coherence and Cognition in Children with Fetal Alcohol Spectrum Disorder (FASD)-A Quantitative EEG Study.

Magnetic resonance imaging in fetal alcohol spectrum disorder (FASD) children showed altered connectivity, suggesting underlying deficits in networks, which may be related to cognitive outcome. Functional connectivity has been of interest in neurophysiological research with quantitative electroencephalography (QEEG) as useful tool for measuring pathology, not detectable by normal EEG. The aim of this study was to investigate differences in the EEG interhemispheric coherence (ICoh) in children diagnosed with FASD compared with healthy controls and to relate the results to cognitive scores. Analysis of ICoh in 81 FASD children (4-Digit Code) compared with 31 controls. The children underwent cognitive assessment, and EEG was performed and used for analysis. Group comparisons and analysis of covariance interaction models were used to test for differences between FASD and controls but also to look for differences between FASD subgroups. Significant findings were correlated to cognitive scores. Lower ICoh was found in the frontal and temporal derivations in the FASD group. When comparing FASD subgroups, children with fetal alcohol syndrome had lower ICoh occipital. Reduced ICoh in the temporal alpha band was correlated with lower performance IQ in the FASD group. Our findings could imply hypoconnectivity between the hemispheres with impact on cognition. We suggest that EEG coherence analysis could be a sensitive parameter in the detection of electrophysiological abnormalities in FASD with possible clinical relevance. These results may indicate that QEEG could be used as biomarker for FASD. However, further research is needed to determine the role of QEEG analysis in the diagnosis of FASD.

Frequency of epilepsy and pathological EEG findings in a Norwegian sample of children with fetal alcohol spectrum disorder: Impact on cognition and adaptive functioning.

Fetal alcohol spectrum disorder (FASD) comprises a combination of developmental, cognitive, and behavioral disabilities that occur in children exposed to alcohol prenatally. A higher prevalence of epilepsy and pathological electroencephalographic (EEG) features have also been reported in individuals with FASD. We examined the frequency of epilepsy, pathological EEG findings, and their implications for cognitive and adaptive functioning in children with FASD. We conducted a cross-sectional study of 148 children with FASD who underwent a multidisciplinary assessment and a 120-min EEG recording. Group comparisons and regression analyses were performed to test the associations between epilepsy and pathological EEG findings, FASD subgroups and neurocognitive test results and adaptive functioning. The frequency of epilepsy was 6%, which compares with 0.7% in Norway overall. Seventeen percent of children without epilepsy had pathological EEG findings. Attention-deficit hyperactivity disorder (ADHD) was diagnosed in 64% of the children. Children with epilepsy and/or pathological EEG findings had comparable cognitive and adaptive scores to those with normal EEG. However, children with frontal EEG pathology (without epilepsy) had significantly lower scores on the IQ indices Processing speed and Working memory than FASD children without such findings, irrespective of ADHD comorbidity. There was a greater prevalence of epilepsy among children with FASD than in the general Norwegian population. A greater frequency of EEG pathology was also evident in children without epilepsy, across all FASD subgroups. Irrespective of epilepsy, ADHD comorbidity, and FASD subgroup, children with frontal EEG pathology, despite having a normal total IQ, showed significantly slower processing speed and poorer working memory, which may indicate specific executive function deficits that could affect learning and adaptive functioning.

Rethinking Local Economic Development for Fetal Alcohol Spectrum Disorder in Renosterberg Local Municipality, South Africa

Two towns in Renosterberg Local Municipality (RLM) in the Northern Cape Province of South Africa, Petrusville and Philipstown, have high Fetal Alcohol Spectrum Disorder (FASD) prevalence rates. FASD is linked to poverty and imposes high national economic costs. Thus, it is critical to understand the local economic development (LED) strategies used to mitigate the high prevalence of FASD. Moreover, there is sparse literature examining adult communities where FASD children reside. Understanding these adult communities is important because FASD cannot exist without adult gestational exposure to alcohol consumption. Using a mixed-method approach, this study uses a six-phase analytic approach to investigate the drinking culture and drinking motives in RLM, applied to two cross-sectional in-depth community needs assessments, five in-depth interviews, and three focus groups. This study also evaluates how the RLM targets FASD, as well as binge and risky drinking, in its municipal economic strategy by analysing its Integrated Development Plan (IDP) with respect to an eight-stage policy development process. The results indicate that 57% of respondents expressed concern regarding the unhealthy drinking culture in RLM, 40% felt that the residents of RLM drank in response to unemployment-related hopelessness, and 52% attributed the drinking culture to a lack of hobbies and recreational opportunities. The results of an analysis of the RLM IDP through the lens of Ryder's eight-stage policy development process suggest that the decisive policy development process is not open to the public and that, furthermore, FASD is neglected. A dedicated alcohol consumption census-style study is recommended to broadly capture alcohol consumption in RLM, allowing researchers to identify the exact alcohol consumption patterns and priority areas for the IDP and public health policy. RLM should directly publicise its policy development process so that its IDP is inclusively formulated to address FASD, risky drinking, binge drinking, and gestational alcohol consumption.

Sleep disturbances in Norwegian children with fetal alcohol spectrum disorders (FASD) with and without a diagnosis of attention-deficit hyperactivity disorder or epilepsy.

Fetal alcohol spectrum disorder (FASD) describes a combination of developmental, cognitive, and behavioral disabilities in children with prenatal exposure to alcohol. The literature suggests that there are higher rates of sleep disturbances in these children. Few studies have investigated sleep disturbances in relation to common comorbidities of FASD. We examined the prevalence of disturbed sleep and the relationship between parent-reported sleep problems in different FASD subgroups and comorbidities like epilepsy or attention-deficit hyperactivity disorder (ADHD) and impact on clinical functioning. In this prospective cross-sectional survey, caregivers of 53 children with FASD completed the Sleep Disturbance Scale for Children (SDSC). Information about comorbidities was collected, and EEG and assessment of IQ, daily-life executive and adaptive functioning were performed. Group comparisons and ANCOVA interaction models were used to test the associations between different sleep disturbances and clinical factors that could interfere with sleep. An abnormal sleep score on the SDSC was very common, affecting 79% of children (n= 42) with equal prevalence in all FASD subgroups. Difficulty falling asleep was the most common sleep problem, followed by difficulty staying asleep and waking early. The incidence of epilepsy was 9.4%, with an abnormal EEG seen in 24.5%, and a diagnosis of ADHD in 47.2% of children. The distribution of these conditions was equal in all FASD subgroups. Children with signs of sleep disturbance had poorer working memory, executive function, and adaptive functioning. Children with ADHD had a greater prevalence of sleep disturbance than those without ADHD (OR 1.36; 95% CI 1.03 to 1.79). Problems with sleep are very common in FASD children and seem independent of FASD subgroup and the presence of epilepsy or a pathological EEG finding, while those with ADHD had more sleep problems. The study underscores the importance of screening for sleep disturbances in all children with FASD as these problems may be treatable.

Global intellectual ability and adaptive functioning in children with FASD with and without sentinel facial features

ABSTRACT Background: Fetal Alcohol Spectrum Disorder (FASD) is a neurodevelopmental disorder characterized by cognitive and adaptive impairment. FASF can be presented or not with sentinel facial features (SFF). The presence of such SFF have been positively correlated with cognitive impairment in children with FASD. Objectives: The current study explores difference in global intellectual functioning and how cognition affects adaptive behavior in children with and without SFF. Methods: A total of 88 children and adolescents (55 males, 33 females) with confirmed FASD diagnosis were included in the study, of which 16 had sentinel facial features. Childrens’ neuropsychological functioning was assessed using the Wechsler Intelligence Scale for Children (WISC-V) and The Behavioral Assessment of the Dysexecutive Syndromes for Children (BADS-C). Adaptive behavior was explored through the Adaptive Behavior Assessment System (ABAS-3). Results: Children with SFF performed more poorly in tasks assessing processing speed (t = 2.495, t = .020) and executive functioning (t = 4.147, t = .001). Those children also had lower IQ scores than children without SFF (t = 2.658, t = .016). BADS-C overall scaled score was related to three of the four domains of the ABAS scale (conceptual, social, and practical) but only in the group of FASD children without SFF (B = 0.547, t = .020; B = 0.544,t = .049; B = 0.431,t = .040, respectively). Conclusions: The present study founds poorer cognitive outcomes in children who have FASD with sentinel facial features. In children without SFF, stronger executive functioning is also related to significantly stronger reported conceptual, social, and practical adaptive behaviors. Better understanding of cognitive and adaptive functioning in children with FASD may help in the design of tailored evidenced-based interventions.

Distal tibial trabecular morphometry in a Sprague Dawley rat model of fetal alcohol syndrome: a micro focus X-ray computed tomography case-control study.

intrauterine alcohol exposure has adverse health effects on the offspring, which may result in fetal Alcohol Spectrum Disorders (FASD). The neurological and craniofacial aspects have been well studied; however, long bones have received limited attention despite the short stature reported in FASD children. time-mated (n=13) pregnant Sprague Dawley dams were assigned to either the ethanol (n=5), saline control (n=5) or untreated group (n=3) which received no treatment. The ethanol and saline control dams were treated with 0.015ml/g of 25.2% ethanol or 0.9% saline, respectively. Treatment was for the first 19 days of gestation. Two pups from each dam were used and terminated at 21 days of age. Paired tibiae were harvested. Each bone was scanned using a Nikon XTH 225L 3D-μCT to investigate trabeculae morphometry. the ethanol group had less bone to total volume (BT/TV), thinnest trabeculae (TbTh) which were less spaced (TbSp) compared to the controls. However, number of trabecular (TbN) remained unaffected in all three groups. Tibial length was similar in all three groups; however, the distal metaphysis volume was smallest in the ethanol group. Logistic regression showed that the distal medullary canal area and trabecular separation were the main parameters affected the most in gestational alcohol. The negative correlation of trabecular thickness and spacing in the ethanol group may be a contributor to bone weakness. gestational alcohol exposure affects bone internal morphology in addition to the bone size. Overall, this study supports the findings of clinical observation of small stature in FAS children.

Markers of Neuroinflammation in the Serum of Prepubertal Children with Fetal Alcohol Spectrum Disorders.

Fetal Alcohol Spectrum Disorders (FASD) are the manifestation of the damage caused by alcohol consumption during pregnancy. Children with Fetal Alcohol Syndrome (FAS), the extreme FASD manifestation, show both facial dysmorphology and mental retardation. Alcohol consumed during gestational age prejudices brain development by reducing, among others, the synthesis and release of neurotrophic factors and neuroinflammatory markers. Alcohol drinking also induces oxidative stress. The present study aimed to investigate the potential association between neurotrophins, neuroinflammation, and oxidative stress in 12 prepubertal male and female FASD children diagnosed as FAS or partial FAS (pFAS). Accordingly, we analyzed, in the serum, the level of BDNF and NGF and the oxidative stress, as Free Oxygen Radicals Test (FORT) and Free Oxygen Radicals Defense (FORD). Moreover, serum levels of inflammatory mediators (IL-1α, IL-2, IL-6, IL-10, IL-12, MCP-1, TGF-β, and TNF-α) involved in neuroinflammatory and oxidative processes have been investigated. We demonstrated low serum levels of NGF and BDNF in pre-pubertal FASD children with respect to healthy controls. These changes were associated with higher serum presence of TNF- α and IL-1α. Quite interestingly, an elevation in the FORD was also found despite normal FORT levels. Moreover, we found a potentiation of IL-1α, IL-2, IL-10, and IL-1α1 in the analyzed female compared to male children. The present investigation shows an imbalance in the peripheral neuroimmune pathways that could be used in children as early biomarkers of the deficits observed in FASD.

Influence of COMT (rs4680) and DRD2 (rs1076560, rs1800497) Gene Polymorphisms on Safety and Efficacy of Methylphenidate Treatment in Children with Fetal Alcohol Spectrum Disorders

Fetal alcohol spectrum disorders (FASD) in a course of high prenatal alcohol exposure (hPAE) are among the most common causes of developmental disorders. The main reason for pharmacological treatment of FASD children is attention deficit hyperactivity disorder (ADHD), and methylphenidate (MPH) is the drug of choice. The aim of the study was to assess whether children born of hPAE with ADHD, with or without morphological FASD, differ in terms of catechol-O-methyltransferase (COMT) and dopamine receptor D2 (DRD2) gene polymorphisms, and if genetic predisposition affects response and safety of MPH treatment. The polymorphisms of COMT (rs4680) and DRD2 (rs1076560, rs1800497) were analyzed in DNA samples. A borderline significance was found for the correlation between MPH side effects and the G allele of COMT (rs4680) (p = 0.04994) in all ADHD children. No effect of COMT (rs4680) and DRD2 (rs1076560, rs1800497) polymorphisms and the treatment efficacy was observed. The analyzed DRD2 and COMT gene polymorphisms seem to play no role in MPH efficacy in ADHD children with hPAE, while low-activity COMT (Met158) variant carriers may be more intolerant to MPH. The MPH treatment is effective in ADHD independent of FASD, although the ADHD-FASD variant requires higher doses to be successful. These results may help in optimization and individualization in child psychiatry.

Estimating the community prevalence, child traits, and maternal risk factors of fetal alcohol spectrum disorders (FASD) from a random sample of school children

ObjectiveUtilize a random sample to estimate the prevalence, child traits, and maternal risk for fetal alcohol spectrum disorders (FASD) in a Southeastern United States county. MethodsFrom all first-grade students (n = 1073) a simple random sample was drawn, and 32 % (n = 231) were consented. All 231 children were examined for dysmorphology and growth, 84 were tested and rated on neurobehavior, and 72 mothers were interviewed for maternal risk. ResultsSignificant differences (α = .05) between the physical traits of children diagnosed with FASD and the entire sample were height, weight, head circumference, body mass index, and total dysmorphology scores, and all three cardinal features of fetal alcohol syndrome: palpebral fissure length, smooth philtrum, and narrow vermilion. Intellectual function and inhibition were not significantly different between FASD and typically-functioning children, but two executive function measures and one visual/spatial measure approached significance (α = .10). Three behavioral measures were significantly worse for the FASD group: parent-rated problems of communication, daily living, and socialization. Significant maternal risk factors reported were postpartum depression, frequency of drinking, and recovery from problem drinking. The prevalence of FASD was 71.4 per 1,000 or 7.1 %. This rate falls clearly within the prevalence range identified in eight larger samples of other communities in the Collaboration on FASD Prevalence (CoFASP) study in four regions of the United States. ConclusionCareful and detailed clinical evaluation of children from small random samples can be useful for estimating the prevalence and traits of FASD in a community.

Sleep disturbance as a predictor of anxiety in children with Fetal Alcohol Spectrum Disorders and typically developing children

BackgroundHigh levels of anxiety and sleep problems are common features of Fetal Alcohol Spectrum Disorders (FASD). The strong association between sleep and anxiety has been documented in typically developing (TD) populations and is thought to be bidirectional. The association between sleep and anxiety in children with FASD has not yet been examined. MethodsCaregivers of children with FASD (n = 91) and TD children (n = 103) aged 6–16 completed the Children’s Sleep Habits Questionnaire (CSHQ), Spence Children’s Anxiety Scale (SCAS), and a background questionnaire. Hierarchical multiple regression analyses, group comparisons and ANCOVA interaction models were used to test the associations between sleep and anxiety within and between the two groups. ResultsSleep disturbances and anxiety were at clinical levels for the majority of the FASD group, and significantly higher in the FASD group than the TD group. After controlling for age and sex, 27 % of the variance in anxiety scores in TD children was attributable to sleep problems, and 33 % in children with FASD. ConclusionThis study highlights associations between parent-reported sleep and anxiety in FASD. Sleep disturbances were significant predictors of anxiety in both children with FASD and in TD children. Given the importance of sleep to healthy neurodevelopment, there is a pressing need for sleep intervention studies in children with FASD. Early identification and intervention for sleep problems in this condition should be a therapeutic priority.

Prenatal Ethanol Exposure Leads to Attention Deficits in Both Male and Female Rats.

BackgroundPrenatal ethanol exposure (PE) causes multiple behavioral and cognitive deficits, collectively referred to as fetal alcohol spectrum disorders (FASD). Studies show that 49–94% of FASD children exhibit attention deficits, even when they have normal IQs or lack severe facial deformities, suggesting that attention deficits could be caused by even moderate prenatal exposure to alcohol, of which the underlying neural mechanisms are still unclear. A valid rodent model could help elucidate this phenomenon.Materials and MethodsA second-trimester equivalent binge drinking PE model was utilized. Pregnant Sprague Dawley rats were administered with 15% (w/v) ethanol (6 g/kg/day, via gastric gavage) during gestational days 8–20, and their offspring were the subjects in the present study. A modified 2-choice reaction time (2-CRT) task was used to illustrate possible attention deficits, including increased action impulsivity and lapses of attention. Enhanced impulsivity was reflected by more premature responses while increased lapses of attention were manifested as more incorrect responses and/or greater variability of reaction time, demonstrated by more skewed distributions of reaction time. Ten-week-old male and female rats were tested for three sessions following 16–19 days of training.ResultsOur PE paradigm caused no major teratogenic effects. PE led to increased impulsivity exhibited as greater premature responses and augmented lapses of attention shown by greater skewnesses of reaction time distributions, relative to controls. The deficits were observed in both PE male and female rats. Interestingly, in males, the attention deficits were detected only when the 2-CRT task was relatively difficult whereas in females they were detected even when the task was at a less demanding level.ConclusionWe show that the binge drinking pattern of PE led to attention deficits in both sexes of rats even though no major teratogenic effects were observed. Therefore, this rodent model can be used to study neural mechanisms underlying attention deficits caused by PE and to explore effective intervention approaches for FASD.

Fetal Alcohol Spectrum Disorders in a Pacific Southwest City: Maternal and Child Characteristics.

There are limited data on the characteristics of children with fetal alcohol spectrum disorders (FASD) and their mothers from the general population in the United States. During the 2012 and 2013 academic years, first-grade children in a large urban Pacific Southwest city were invited to participate in a study to estimate the prevalence of FASD. Children who screened positive on weight, height, or head circumference ≤25th centile or on parental report of developmental concerns were selected for evaluation, along with a random sample of those who screened negative. These children were examined for dysmorphology and neurobehavior and their mothers or collateral sources were interviewed. Children were classified as fetal alcohol syndrome (FAS), partial fetal alcohol syndrome (pFAS), alcohol-related neurodevelopmental disorder (ARND), or No FASD. A total of 854 children were evaluated; 5 FAS, 44 pFAS, 44 ARND, and 761 No FASD. Children with FAS or pFAS were more likely to have dysmorphic features, and 32/49 (65.3%) of those met criteria for neurobehavioral impairment on cognitive measures with or without behavioral deficits. In contrast, 28/44 (63.6%) of children with ARND met criteria on behavioral measures alone. Mothers of FASD children were more likely to recognize pregnancy later, be unmarried, and report other substance use or psychiatric disorders, but did not differ on age, socioeconomic status, education, or parity. Mothers of FASD children reported more drinks/drinking day each trimester. The risk of FASD was elevated with increasing number of drinks/drinking day prior to pregnancy recognition, even at the level of 1 drink per day (adjusted odds ratio 3.802, 95% confidence interval 1.634, 8.374). Data from this general population sample in a large urban region in the United States demonstrate the variability of expression of FASD and point to risk and protective factors for mothers in this setting.

Fetal alcohol exposure: when placenta would help to the early diagnosis of child brain impairments

Alcohol consumption during pregnancy constitutes a major cause of neurodevelopmental and behavioral disabilities. Whereas it is possible for clinicians to establish a perinatal diagnosis of fetal alcohol syndrome, the more severe expression of fetal alcohol spectrum disorder (FASD), most FASD children are late or mis-diagnosed due to a lack of clear morphological and neurodevelopmental abnormalities. Several precious years of care are consequently lost. Recent data revealed a functional placenta-brain axis involved in the control of the fetal brain angiogenesis which is impaired by in utero alcohol exposure. Because in the developing fetal brain a correct angiogenesis is required for a correct neurodevelopment, these preclinical and clinical advances pave the way for a new generation of placental biomarkers for early diagnosis of FASD.

"The Dop System of Alcohol Distribution is Dead, but It's Legacy Lives On…."

Objective: Determine the prevalence of Dop, a system of labor payment via alcoholic beverages, in a South African province, and its influence on maternal drinking and fetal alcohol spectrum disorders (FASD). Methods: Data from studies of FASD epidemiology were analyzed. Results: Forty-two percent to 67% of mothers reported drinking. In 1999, 5% of women reported Dop allocations in their lifetime: 14% of mothers of FASD children and 1% of controls. In 2010, 1.1% of mothers reported lifetime Dop: 1.6% of FASD mothers and 0.7% of controls. Commercial alcohol sales have replaced the Dop system. Total FASD rates remained high in rural areas in 2010 and rose in urban settings. Urban rates of total FASD surpassed rural area rates in 2010. Correlation analysis did not reveal a strong or significant, direct relationship between Dop experience and heavy drinking (r = 0.123, p < 0.001, r2 = 0.015), or the diagnosis of FASD in children (OR = 0.003, p = 0.183). Conclusion: Dop, as a systematic practice, is dead and does not have a direct influence on alcohol availability, heavy maternal drinking, or the probability of an FASD diagnosis. Nevertheless, today’s problematic drinking patterns were heavily influenced (shaped) by Dop and have negatively impacted the prevalence and severity of FASD.

Postnatal nutritional treatment of neurocognitive deficits in fetal alcohol spectrum disorder.

Ethanol is the most important teratogen agent in humans. Prenatal alcohol exposure can lead to a wide range of adverse effects, which are broadly termed as fetal alcohol spectrum disorder (FASD). The most severe consequence of maternal alcohol abuse is the development of fetal alcohol syndrome, defined by growth retardation, facial malformations, and central nervous system impairment expressed as microcephaly and neurodevelopment abnormalities. These alterations generate a broad range of cognitive abnormalities such as learning disabilities and hyperactivity and behavioural problems. Socioeconomic status, ethnicity, differences in genetic susceptibility related to ethanol metabolism, alcohol consumption patterns, obstetric problems, and environmental influences like maternal nutrition, stress, and other co-administered drugs are all factors that may influence FASD manifestations. Recently, much attention has been paid to the role of nutrition as a protective factor against alcohol teratogenicity. There are a great number of papers related to nutritional treatment of nutritional deficits due to several factors associated with maternal consumption of alcohol and with eating and social disorders in FASD children. Although research showed the clinical benefits of nutritional interventions, most of work was in animal models, in a preclinical phase, or in the prenatal period. However, a minimum number of studies refer to postnatal nutrition treatment of neurodevelopmental deficits. Nutritional supplementation in children with FASD has a dual objective: to overcome nutritional deficiencies and to reverse or improve the cognitive deleterious effects of prenatal alcohol exposure. Further research is necessary to confirm positive results, to determine optimal amounts of nutrients needed in supplementation, and to investigate the collective effects of simultaneous multiple-nutrient supplementation.

DNA methylation-independent growth restriction and altered developmental programming in a mouse model of preconception male alcohol exposure

ABSTRACTThe preconception environment is a significant modifier of dysgenesis and the development of environmentally-induced disease. To date, fetal alcohol spectrum disorders (FASDs) have been exclusively associated with maternal exposures, yet emerging evidence suggests male-inherited alterations in the developmental program of sperm may be relevant to the growth-restriction phenotypes of this condition. Using a mouse model of voluntary consumption, we find chronic preconception male ethanol exposure associates with fetal growth restriction, decreased placental efficiency, abnormalities in cholesterol trafficking, sex-specific alterations in the genetic pathways regulating hepatic fibrosis, and disruptions in the regulation of imprinted genes. Alterations in the DNA methylation profiles of imprinted loci have been identified in clinical studies of alcoholic sperm, suggesting the legacy of paternal drinking may transmit via heritable disruptions in the regulation of imprinted genes. However, the capacity of sperm-inherited changes in DNA methylation to broadly transmit environmentally-induced phenotypes remains unconfirmed. Using bisulphite mutagenesis and second-generation deep sequencing, we find no evidence to suggest that these phenotypes or any of the associated transcriptional changes are linked to alterations in the sperm-inherited DNA methylation profile. These observations are consistent with recent studies examining the male transmission of diet-induced phenotypes and emphasize the importance of epigenetic mechanisms of paternal inheritance beyond DNA methylation. This study challenges the singular importance of maternal alcohol exposures and suggests paternal alcohol abuse is a significant, yet overlooked epidemiological factor complicit in the genesis of alcohol-induced growth defects, and may provide mechanistic insight into the failure of FASD children to thrive postnatally.

Fetal Alcohol Spectrum Disorders: An Overview from the Glia Perspective.

Alcohol consumption during pregnancy can produce a variety of central nervous system (CNS) abnormalities in the offspring resulting in a broad spectrum of cognitive and behavioral impairments that constitute the most severe and long-lasting effects observed in fetal alcohol spectrum disorders (FASD). Alcohol-induced abnormalities in glial cells have been suspected of contributing to the adverse effects of alcohol on the developing brain for several years, although much research still needs to be done to causally link the effects of alcohol on specific brain structures and behavior to alterations in glial cell development and function. Damage to radial glia due to prenatal alcohol exposure may underlie observations of abnormal neuronal and glial migration in humans with Fetal Alcohol Syndrome (FAS), as well as primate and rodent models of FAS. A reduction in cell number and altered development has been reported for several glial cell types in animal models of FAS. In utero alcohol exposure can cause microencephaly when alcohol exposure occurs during the brain growth spurt a period characterized by rapid astrocyte proliferation and maturation; since astrocytes are the most abundant cells in the brain, microenchephaly may be caused by reduced astrocyte proliferation or survival, as observed in in vitro and in vivo studies. Delayed oligodendrocyte development and increased oligodendrocyte precursor apoptosis has also been reported in experimental models of FASD, which may be linked to altered myelination/white matter integrity found in FASD children. Children with FAS exhibit hypoplasia of the corpus callosum and anterior commissure, two areas requiring guidance from glial cells and proper maturation of oligodendrocytes. Finally, developmental alcohol exposure disrupts microglial function and induces microglial apoptosis; given the role of microglia in synaptic pruning during brain development, the effects of alcohol on microglia may be involved in the abnormal brain plasticity reported in FASD. The consequences of prenatal alcohol exposure on glial cells, including radial glia and other transient glial structures present in the developing brain, astrocytes, oligodendrocytes and their precursors, and microglia contributes to abnormal neuronal development, reduced neuron survival and disrupted brain architecture and connectivity. This review highlights the CNS structural abnormalities caused by in utero alcohol exposure and outlines which abnormalities are likely mediated by alcohol effects on glial cell development and function.

Maternal nutritional status as a contributing factor for the risk of fetal alcohol spectrum disorders.

Compare nutritional status of 57 South African mothers of children with fetal alcohol spectrum disorders (FASD) with 148 mothers of controls. Dietary data were analyzed for macronutrients, micronutrients, and fats via estimated average requirements (EAR) and adequate intakes (AI) for pregnant women. Virtually all mothers were likely deficient on most micronutrients by either EAR (<50%) or AI values. Mothers of FASD children consumed more of 13 of 25 micronutrients. For percentage below EAR, only vitamin D was significantly higher for FASD mothers. Despite no difference in total food intake, control mothers had a higher mean body mass index (BMI) than FASD mothers. Maternal BMI is more significant for positive child outcomes than any individual nutrient. Most mothers have inadequate dietary intake. Minor advantages in nutrient intake are overpowered by teratogenic effects of alcohol. Further study is needed of the interaction of alcohol, maternal nutrition, and metabolism.

Associative DNA methylation changes in children with prenatal alcohol exposure.

Prenatal alcohol exposure (PAE) can cause fetal alcohol spectrum disorders (FASD). Previously, we assessed PAE in brain tissue from mouse models, however whether these changes are present in humans remains unknown. In this report, we show some identical changes in DNA methylation in the buccal swabs of six children with FASD using the 450K array. The changes occur in genes related to protocadherins, glutamatergic synapses, and hippo signaling. The results were found to be similar in another heterogeneous replication group of six FASD children. The replicated results suggest that children born with FASD have unique DNA methylation defects that can be influenced by sex and medication exposure. Ultimately, with future clinical development, assessment of DNA methylation from buccal swabs can provide a novel strategy for the diagnosis of FASD.

Prevalence of fetal alcohol syndrome in a South African city with a predominantly Black African population.

Fetal alcohol spectrum disorder (FASD) and fetal alcohol syndrome (FAS) are common in some South African populations, notably those of mixed ancestry descent in rural areas and small towns. Little is known about FAS/FASD prevalence in the majority of South Africans: city dwellers of Black African ethnicity. This study describes the prevalence of FAS in a South African city, comparing 2 suburbs with predominantly mixed ancestry (Roodepan) and Black African (Galeshewe) populations that house over 60% of the city population. We conducted a tiered, active case ascertainment study for the prevalence of FAS and also detected some less clinically specific FASD cases. All first-grade learners in the 2 suburbs were eligible for anthropometric screening, and screen-positive learners were assessed for dysmorphic features of FAS. Those with suggestive clinical features received neurocognitive assessment, and maternal or collateral interview. Final diagnosis was made following a case conference. Complete ascertainment of FAS status was made in 1,503 (94.7%) of 1,587 eligible learners (435 in Roodepan and 1,152 in Galeshewe). Overall, FAS was diagnosed in 83 (5.5%, 95% confidence interval [CI]=4.4 to 6.8) learners and FASD in 96 (6.4%, 95% CI=5.2 to 7.7). Levels of FAS were high in both areas: 26 (6.3%, 95% CI=4.2 to 9.2) learners from Roodepan, compared to 57 (5.2%, 95% CI=4.0 to 6.7) from Galeshewe (p=0.39). No cases were previously diagnosed. The mortality rate for mothers of FASD children from Galeshewe was 19 of 65 (29%), compared to 3 of 31 (9.7%; p=0.03) for Roodepan. Interviewed mothers in Galeshewe were older and had higher body mass index. Prevalence of FAS is high in both Galeshewe and Roodepan, and the lack of prior diagnoses indicates that awareness remains low. The maternal mortality rate was especially high in Galeshewe. The unexpectedly high burden of FAS in an urban area with predominantly Black African population mandates extension of surveillance and intervention measures in southern Africa.