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To complement the 2005 Annual Clinical Focus on medical genomics, AFP will be publishing a series of short reviews on genetic syndromes. This series was designed to increase awareness of these diseases so that family physicians can recognize and diagnose children with these disorders and understand the kind of care they might require in the future. The second review in this series discusses fetal alcohol syndrome and fetal alcohol spectrum disorders.
This article describes the proceedings of the 2006 Annual Meeting of the Fetal Alcohol Spectrum Disorders Study Group (FASDSG), which was held in Baltimore, Maryland on June 24, 2006. The meeting was held in conjunction with the annual meeting of the Research Society on Alcoholism and was supported by a grant from the National Institute on Alcohol Abuse and Alcoholism. The 2005-2006 FASDSG officers, Daniel J. Bonthius (President), Heather Carmichael Olson (Vice-President), and Jennifer Thomas (Secretary-Treasurer), organized the meeting. Nationally prominent speakers delivered plenary lectures on topics of newborn screening, ethics, and neuroscience. Selected members of the FASDSG provided brief scientific data (FASt) reports, describing new research findings. Representatives from national agencies involved in fetal alcohol syndrome (FAS) research, treatment, and prevention provided updates regarding priorities, funding, and agency activities. Presentations were also made by the 2006 Student Merit Award recipient and by the 2006 Rosett Award recipient. The meeting served as a forum for clinicians, neuroscientists, psychologists, social scientists, and other professionals to discuss recent advances in FAS research and to identify the most important gaps in the understanding of alcohol-induced teratology.
BACKGROUND: Prenatal alcohol exposure affects brain structure and function. This study examined brain metabolism using magnetic resonance spectroscopy (MRS) and searched for regions of specific vulnerability in adolescents and young adults prenatally exposed to alcohol. METHODS: Ten adolescents and young adults with confirmed heavy prenatal alcohol exposure and a diagnosis within the fetal alcohol spectrum disorders (FASD) were included. Three of them had fetal alcohol syndrome (FAS), 3 had partial FAS (PFAS), and 4 had alcohol-related neurobehavioral disorder (ARND). The control group consisted of 10 adolescents matched for age, sex, head circumference, handedness, and body mass. Exclusionary criteria were learning disorders and prenatal alcohol exposure. Three-dimensional (1)H magnetic resonance spectroscopic imaging ((1)H MRSI) was performed in the cerebrum and cerebellum. Metabolite ratios N-acetylaspartate/choline (NAA/Cho), NAA/creatine (Cr) and Cho/Cr, and absolute metabolite intensities were calculated for several anatomic regions. RESULTS: In patients with FASD, lower NAA/Cho and/or NAA/Cr compared with controls were found in parietal and frontal cortices, frontal white matter, corpus callosum, thalamus, and cerebellar dentate nucleus. There was an increase in the absolute intensity of the glial markers Cho and Cr but no change in the neuronal marker NAA. CONCLUSIONS: Our results suggest that prenatal alcohol exposure alters brain metabolism in a long-standing or permanent manner in multiple brain areas. These changes are in accordance with previous findings from structural and functional studies. Metabolic alterations represent changes in the glial cell pool rather than in the neurons.
OBJECTIVE: To provide an overview of the animal and human research literature on the link between fetal alcohol spectrum disorder (FASD) and attention-deficit hyperactivity disorder (ADHD). METHOD: We conducted a comprehensive literature review that addressed the history of, and current research on, fetal alcohol syndrome (FAS) and FASD, as well as that on ADHD in children. RESULTS: In animal and human research, there is emerging clinical, neuropsychological, and neurochemical evidence of a link between FASD and ADHD. CONCLUSIONS: The evidence of the link between these 2 conditions has implications for clinical management. The clinical quality of ADHD in children with FASD often differs from that of children without FASD. For children with FASD, ADHD is more likely to be the earlier-onset, inattention subtype, with comorbid developmental, psychiatric, and medical conditions. Children with FASD are commonly not mentally retarded but present complex learning disabilities, especially a mixed receptive-expressive language disorder with deficits in social cognition and communication (reminiscent of sensory aphasia and apraxia), working memory problems, and frequently, a mathematics disorder. Comorbid psychiatric conditions include anxiety, mood, conduct, or explosive disorders. As well, cardiac, renal, or skeletal problems are more likely to be present. Because these children have a disturbance in brain neurochemistry, or even brain structure (that is, in the corpus callosum), their response to standard psychostimulant medication can be quite unpredictable.
BACKGROUND: There has been considerable effort expended on defining neurobehavioral characteristics of children with fetal alcohol spectrum disorders (FASD). Children with FASD display a range of cognitive deficits and behavioral problems. In this article, we report on the neurobehavioral characteristics of children with FASD in selected communities in Italy. It was expected that both inattentive and hyperactive/impulsive characteristics would discriminate children with FASD from controls and that the groups would also differ on intellectual functioning, language comprehension, and academic skills. METHODS: Eighty-two children, 22 diagnosed with FASD and 60 control children, participated in this study. The children were administered tests of nonverbal reasoning, language comprehension, academic achievement, and behavior. RESULTS: On tests of nonverbal reasoning and language comprehension, the FASD group earned lower scores than did controls. Moreover, on a test of academic achievement the FASD group scored lower. When comparing these 2 groups on disruptive behavioral symptomatology, similar results were obtained, the FASD group showing greater attentional difficulties and hyperactivity/impulsivity behaviors and more overall behavioral problems. Stepwise logistic regression analysis showed that a model containing inattention and error scores on the language comprehension task correctly classified 85% of the participants. Compared with the control group, a significantly greater proportion of children with FASD met the Diagnostic and Statistical Manual of Mental Disorders-fourth edition (DSM-IV) criteria of ADD, inattentive type, as reported by teachers. In contrast, hyperactive symptoms among children with FASD were comparable with the control group. Teachers rated children with FASD as having more inattentive behaviors and as performing lower in academic skills than controls. The association between reported hyperactivity symptoms and achievement scores was nonsignificant for both language and math scores, suggesting that it is not the hyperactivity causing problems, but the child's inattention. CONCLUSIONS: This research indicates that a nonclinic-referred sample of Italian children with FASD display a profile of neurobehavioral functioning consistent with that reported by other researchers. Furthermore, the neurobehavioral characteristic most identified with children diagnosed with FASD was inattention followed by hyperactivity.
The goal of this report is to critically review research on executive functioning (EF) and working memory in individuals with fetal alcohol spectrum disorder (FASD). Individuals with FASD exhibit EF deficits in the areas of cognitive flexibility, planning and strategy use, verbal reasoning, some aspects of inhibition, set shifting, fluency, working memory, and, recently, on tests of emotion-related or hot EF. Some researchers have linked prenatal alcohol exposure to abnormalities in the development of the frontal cortex of affected individuals or animals. One common finding is that these EF deficits persist regardless of whether the individual has facial dysmorphology. Furthermore, EF deficits are not simply due to a low IQ in these individuals. More research with larger sample sizes, smaller age ranges, and consistent measurement tools is needed in this area to ameliorate some inconsistencies in the literature. Furthermore, researchers should now focus on studying the pattern of weakness in EF in individuals with FASD as well as relations among working memory and EF, which will help to identify specific areas of weakness, to enhance diagnosis, and to improve treatment. There is limited research on the development of EF in individuals with FASD, which can have important implications for understanding of how these deficits unfold from childhood through adulthood.
OBJECTIVE: This study was carried out to examine fetal alcohol spectrum disorders (FASD) among Japanese children of alcoholic mothers. This is the first report concerning FASD in Japan. METHODS: The subjects were 30 alcoholic women who were inpatients in the Kurihama Alcoholism Center and had given birth to children. They were subjected to a semi-structured interview by the author. Sixty healthy women who had not drunk during pregnancy were used as a control group, and they also underwent semi-structured interviews. The alcoholic women were divided into two groups, 13 who drunk during pregnancies and 17 who did not drink. Twenty children experienced of prenatal alcohol exposure and 40 children did not. The three groups; i.e., 13 alcoholic mothers who had drunk during pregnancy and their 20 children (ALD group), 17 alcoholic mothers who had not drunk during pregnancy and their 40 children (ALND group) and 60 non-alcoholic control mothers and their 80 children (Control group), were compared concerning the mothers' drinking problems and abnormal deliveries, children's birth weights, congenital abnormalities, abnormalities of the central nervous system and psychological problems. RESULTS: The mean age of onset of problem drinking of the mothers in the ALD group was significantly lower than that in the mothers of the ALND group, and some of the mothers in the ALD group showed alcohol dependence before their pregnancies. The mean birth weights of the children of the ALD group, ALND group and Control group were 2816 g, 3128 g and 3142 g, respectively and the differences were significant. The children of the ALD group had significantly more abnormal birth episodes, developmental retardation and psychiatric symptoms than those in the other two groups. Among 20 children in the ALD group, FASD was suspected in 6 children (10% of the children of alcoholic mothers). Six children had low birth weights, abnormal birth episodes, mental retardation and psychiatric symptoms. CONCLUSION: One third of the Japanese children of alcoholic mothers had experiences of prenatal alcohol exposure and 10% of them had suspected FASD abnormalities.
PURPOSE: The incidence of fetal alcohol spectrum disorders (FASD) is increasing, even though it is 100% preventable. This study examined use of, knowledge about, and attitudes toward alcohol of women requesting emergency contraception (EC) and/or a pregnancy test, and evaluated whether a brief intervention would be effective in educating them about the risks of FASD. DATA SOURCES: Fifty women from two outpatient clinics participated. Information was collected on demographic and personal health habits, alcohol use, and knowledge of and attitudes toward alcohol. As a brief intervention to increase knowledge about FASD, participants read a short pamphlet about the risks of alcohol exposure in pregnancy and then completed a post-test questionnaire. Descriptive statistics, including means, standard deviations, and skewness, were calculated for all variables. Pearson correlations were computed to assess relationships between demographic/lifestyle variables and attitudes toward and knowledge about alcohol. Paired t-tests were used to analyze the relationship between pretest and post-test knowledge scores. CONCLUSIONS: The majority of participants were single (76%), college educated (94%), and received EC at the clinic visit (60%). The average age was 24 years. Slightly over half (52%) reported drinking beer at least once a week, with one to six cans on occasion. Younger women expressed more tolerant attitudes toward alcohol use (p= .02) and drank significantly more beer on occasion (p= .015). Women who reported drinking alcohol when they last had sex were significantly (p= .017) less tolerant in their attitudes toward alcohol use. The intervention used in this study was effective in communicating knowledge about FASD to this population (p < .0001). IMPLICATIONS FOR PRACTICE: These findings suggest that young women may be engaging in behaviors that could put potential offspring at risk for exposure to alcohol. Clinicians are advised to take a thorough history to determine alcohol use in all women of childbearing age and to provide information regarding FASD prevention.
BACKGROUND: The adverse effects of alcohol on the developing human represent a spectrum of structural anomalies and behavioral and neurocognitive disabilities, most accurately termed fetal alcohol spectrum disorders (FASD). The first descriptions in the modern medical literature of a distinctly recognizable pattern of malformations associated with maternal alcohol abuse were reported in 1968 and 1973. Since that time, substantial progress has been made in developing specific criteria for defining and diagnosing this condition. Two sets of diagnostic criteria are now used most widely for evaluation of children with potential diagnoses in the FASD continuum, ie, the 1996 Institute of Medicine (IOM) criteria and the Washington criteria. Although both approaches have improved the clinical delineation of FASD, both suffer from significant drawbacks in their practical application in pediatric practice. OBJECTIVE: The purpose of this report is to present specific clarifications of the 1996 IOM criteria for the diagnosis of FASD, to facilitate their practical application in clinical pediatric practice. METHODS: A large cohort of children who were prenatally exposed to alcohol were identified, through active case-ascertainment methods, in 6 Native American communities in the United States and 1 community in the Western Cape Province of South Africa. The children and their families underwent standardized multidisciplinary evaluations, including a dysmorphology examination, developmental and neuropsychologic testing, and a structured maternal interview, which gathered data about prenatal drinking practices and other demographic and family information. Data for these subjects were analyzed, and revisions and clarifications of the existing IOM FASD diagnostic categories were formulated on the basis of the results. RESULTS: The revised IOM method defined accurately and completely the spectrum of disabilities among the children in our study. On the basis of this experience, we propose specific diagnostic criteria for fetal alcohol syndrome and partial fetal alcohol syndrome. We also define alcohol-related birth defects and alcohol-related neurodevelopmental disorder from a practical standpoint. CONCLUSIONS: The 1996 IOM criteria remain the most appropriate diagnostic approach for children prenatally exposed to alcohol. The proposed revisions presented here make these criteria applicable in clinical pediatric practice.
In utero exposure to alcohol can have numerous adverse effects on a developing fetus. These effects represent a spectrum of structural anomalies and neurocognitive and behavioral disabilities that have recently been termed fetal alcohol spectrum disorders (FASD). Children at the most severe end of this spectrum and displaying the complete phenotype of characteristic facial anomalies, growth retardation and developmental abnormalities of the central nervous system are defined as having fetal alcohol syndrome (FAS). While FAS is the most readily clinically recognized form of FASD, other categories within the continuum of adverse effects due to prenatal alcohol exposure are becoming better defined. These include partial fetal alcohol syndrome (PFAS), alcohol-related birth defects (ARBD) and alcohol-related neurodevelopmental disorder (ARND). As more is learned regarding the exact manifestations of alcohol on brain development, these classifications may be expanded and/or refined. Because FASD represents a major public health concern, early recognition of at-risk children is important for initiating interventional strategies. Thus, the purpose of this report is to educate practicing physicians about the recognizable phenotypes of FASD in order to accurately identify these children and implement the most appropriate management plans.
This study examined child characteristics and family factors as predictors of stress in the biological or adoptive parents of 6- to 12-year-old children with fetal alcohol spectrum disorders (FASDs). Impaired executive functioning, poorer adaptive functioning, externalizing and internalizing behavior problems, and adoptive parent status all made significant and independent contributions to the prediction of higher levels of child domain stress, as reported by parents on the Parenting Stress Index. Biological parent status and fewer family resources were associated with higher levels of parent domain stress. Teacher ratings of the child"s executive functioning impairments and externalizing and internalizing behavior problems also were associated with parent reports of child domain stress. Findings highlight the need to provide support not only to children with FASDs, but to their caregivers as well.
The adverse effects of alcohol on the developing human comprise a spectrum of structural anomalies and behavioral and neurocognitive disabilities, most accurately termed fetal alcohol spectrum disorders (FASD). We previously have proposed revisions to the 1996 Institute of Medicine Diagnostic Criteria for diagnoses in the FASD continuum [fetal alcohol syndrome (FAS), partial fetal alcohol syndrome (PFAS), alcohol related birth defects (ARBD), and alcohol related neurodevelopmental disorder (ARND)], allowing for more reproducible and accurate FASD diagnosis in a clinical setting [Hoyme et al., 2005]. The NIAAA recently has coordinated and funded an international consortium of projects aimed at more complete characterization of the teratogenic spectrum of alcohol. One of the projects sites is in Finland. The aims of this project are: (1) to completely clinically characterize the structural and learning/behavioral phenotypes of a large cohort of older children and adolescents with moderate to severe disability within the FASD continuum; (2) to correlate FASD dysmorphology and behavioral phenotypes with CNS structure and function (i.e., MRS, MRI correlations); (3) to compare the phenotype of a genetically homogeneous population of Finnish children with FASD to that observed in other populations. We have recently completed dysmorphology examination and parent/guardian interviews of the 77 children in the Finnish cohort. The purpose of this report is to present historical and morphometric data on these patients, thereby more completely delineating the clinical spectrum of FASD in older children and adolescents, contrasting the phenotype with that described in other populations and examining whether a weighted dysmorphology score could be used as a clinical and research adjunct when fetal alcohol exposure is being suspected. All children were previously diagnosed with FASD by an experienced pediatric specialist in Finland, and all were exposed to significant maternal alcohol abuse prenatally. The sex ratio of the cohort was 0.38 (male: female) and ages ranged from 8 to 20 years, with a mean of 13 years. After application of the Revised IOM Diagnostic Criteria, 53% of the subjects were diagnosed as having FAS, 30% PFAS, 12% ARND, and 5% other diagnoses. Of note, although a family history of mental retardation or birth defects was rare, 43% of the children had one or more sibling who also carried a diagnosis of FAS. Eighty-nine percent of the mothers smoked cigarettes during gestation; other teratogenic exposures were rare. Almost none had undergone genetics evaluation in the past. Almost all of the subjects had resided in multiple foster placements since early childhood and had been followed regularly by pediatric specialists. Although 11% were born prematurely, 70% demonstrated prenatal growth deficiency, and 45% were microcephalic. Other than growth deficits and the cardinal facial features, the most common major and minor anomalies noted were: camptodactyly (55%), "hockey stick" or other altered palmar creases (51%), refractive errors (40%), strabismus (38%), dental crowding (43%), nail hypoplasia (38%), GU anomalies (22%), and congenital heart defects (18%), "Railroad track" ears were not observed in this population.
BACKGROUND: This work was conducted in an effort to establish an oral intake model system in which the effects of ethanol insult that occur during early stages of embryogenesis can be easily examined and in which agents that may modulate ethanol's teratogenicity can be readily tested in vivo. The model system described utilizes the alcohol deprivation effect to obtain teratogenic levels of maternal ethanol intake on days 7 and 8 of pregnancy in C57Bl/6J mice. Ocular defects including microphthalmia and uveal coloboma, which have previously been shown to result from ethanol administered by gavage or via intraperitoneal injection on these days, served as the developmental end point for this study. The ocular defects are readily identifiable and their degree of severity is expected to correlate with concurrently developing defects of the central nervous system (CNS). METHODS: Female C57Bl/6J mice were maintained on an ethanol-containing (4.8% v/v) liquid diet for 14 days and then mated during a subsequent abstinence period. Mice were then reexposed to ethanol on days 7 and 8 of pregnancy only. Control as well as ethanol-exposed dams were killed on their 14th day of pregnancy. Fetuses were then weighed, measured for crown rump length, photographed, and analyzed for ocular abnormalities. Globe size, palpebral fissure length, and pupil size and shape were noted for both the right and left eyes of all fetuses and informative comparisons were made. RESULTS: This exposure paradigm resulted in peak maternal blood alcohol concentrations that ranged from 170 to 220 mg/dL on gestational day (GD) 8. Compared with the GD 14 fetuses from the normal control group, the pair-fed, acquisition controls, as well as the ethanol-exposed fetuses, were developmentally delayed and had reduced weights. Confirming previous studies, comparison of similarly staged control and treated GD 8 embryos illustrated reductions in the size of the forebrain in the latter. Subsequent ocular malformations were noted in 33% of the right eyes and 25% of the left eyes of the 103 GD 14 ethanol-exposed fetuses examined. This incidence of defects is twice that observed in the control groups. Additionally, it was found that the palpebral fissure length is directly correlated with globe size. CONCLUSIONS: The high incidence of readily identifiable ocular malformations produced by oral ethanol intake in this model and their relevance to human fetal alcohol spectrum disorders (FASD) makes this an excellent system for utilization in experiments involving factors administered to the embryo that might alter ethanol's teratogenic effects. Additionally, the fact that early ethanol insult yields ocular and forebrain abnormalities that are developmentally associated allows efficient specimen selection for subsequent detailed analyses of CNS effects in this in vivo mammalian FASD model.
Magnetic resonance imaging (MRI) and functional MRI studies involving n-back spatial working memory (WM) tasks were conducted in adults and children with Fetal Alcohol Spectrum Disorders (FASD), and in age- and sex-matched controls. FMRI experiments demonstrated consistent activations in regions of the brain associated with working memory. Children with FASD displayed greater inferior-middle frontal lobe activity, while greater superior frontal and parietal lobe activity was observed in controls. Control children also showed an overall increase in frontal lobe activity with increasing task difficulty, while children with FASD showed decreased activity. FASD adults demonstrated less functional brain activity overall, but greater inferior-middle frontal lobe activity during the simpler tasks, relative to controls. Control adults demonstrated greater inferior frontal activity with increasing task difficulty, while this pattern was not consistently observed in FASD adults. All four groups showed increasing activity with increases in task difficulty in the parietal and frontal regions at more superior slice levels. The results suggest impairment in spatial working memory in those with FASD that does not improve with age, and that fMRI may be useful in evaluation of brain function in these individuals.
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BACKGROUND: Prenatal alcohol exposure, which is associated with macrostructural brain abnormalities, neurocognitive deficits, and behavioral disturbances, is characterized as fetal alcohol syndrome (FAS) in severe cases. The only published study thus far using diffusion tensor imaging (DTI) showed microstructural abnormalities in patients with FAS. The current study investigated whether similar abnormalities are present in less severely affected, prenatally exposed patients who did not display all of the typical FAS physical stigmata. METHODS: Subjects included 14 children, ages 10 to 13, with fetal alcohol spectrum disorders (FASD) and 13 matched controls. Cases with full-criteria FAS, mental retardation, or microcephaly were excluded. Subjects underwent MRI scans including DTI. RESULTS: Although cases with microcephaly were excluded, there was a trend toward smaller total cerebral volume in the FASD group (p=0.057, Cohen's d effect size =0.73). Subjects with FASD had greater mean diffusivity (MD) in the isthmus of the corpus callosum than controls (p=0.013, effect size =1.05), suggesting microstructural abnormalities in this region. There were no group differences in 5 other regions of the corpus callosum. Correlations between MD in the isthmus and facial dysmorphology were nonsignificant. CONCLUSIONS: These results suggest that even relatively mild forms of fetal alcohol exposure may be associated with microstructural abnormalities in the posterior corpus callosum that are detectable with DTI.
In Italy, little is known about the spectrum of adverse fetal effects related to maternal alcohol use during pregnancy. In this paper, we report on the phenotype of Italian children with fetal alcohol spectrum disorders (FASD). These data were gathered as part of a field study assessing the prevalence of FASD in children in an in-school study in a rural area near Rome. The purposes of this paper are: (1) to completely characterize the clinical phenotype of a large cohort of Italian children with FASD; (2) to correlate and contrast the phenotype of this population with that observed in other populations and reported in the medical literature; (3) to discuss the drinking habits of Italian women, before, during and after pregnancy; and (4) to suggest mechanisms for intervention and prevention of FASD based on data gathered from this study.
Prenatal alcohol exposure can cause a whole spectrum of central nervous system (CNS) sequelae that persist throughout the life span and manifest in a spectrum of effects from clinically indistinguishable to severely impairing. The greatest impact of alcohol as a teratogen is to the brain-the greatest need is for holistic treatment and management of the associated mental disorders. The interaction of this subtle brain damage with the complex psychosocial circumstances surrounding the birth of a child to a mother with alcohol problems can further compound development and result in costly and devastating social consequences. Research is urgently needed on the chronic neuropsychiatric sequelae of these subtle birth defects of the brain. Identification of these fetal alcohol spectrum disorders (FASD) in the psychiatric nomenclature is a necessary step to focus the attention and resources of the mental health field on this personally and socially significant problem.