Home About us Contact
|
Home About us Contact | ||
|
|
||
Fetal Alcohol Syndrome (fetal + alcohol_syndrome)
Selected AbstractsFETAL ALCOHOL SYNDROME: SAME OLD, SAME OLDADDICTION, Issue 8 2009ERNEST L. ABEL No abstract is available for this article. [source] Prevention of fetal alcohol spectrum disorders,DEVELOPMENTAL DISABILITIES RESEARCH REVIEW, Issue 3 2009R. Louise Floyd Abstract Alcohol use among women of childbearing age is a leading, preventable cause of birth defects and developmental disabilities in the United States. Although most women reduce their alcohol use upon pregnancy recognition, some women report drinking during pregnancy and others may continue to drink prior to realizing they are pregnant. These findings emphasize the need for effective prevention strategies for both pregnant and nonpregnant women who might be at risk for an alcohol-exposed pregnancy (AEP). This report reviews evidence supporting alcohol screening and brief intervention as an effective approach to reducing problem drinking and AEPs that can lead to fetal alcohol spectrum disorders. In addition, this article highlights a recent report of the National Task Force on Fetal Alcohol Syndrome and Fetal Alcohol Effect that describes effective interventions to reduce alcohol use and AEPs, and outlines recommendations on promoting and improving these strategies. Utilizing evidence-based alcohol screening tools and brief counseling for women at risk for an AEP and other effective population-based strategies can help achieve future alcohol-free pregnancies. © 2009 Wiley-Liss, Inc. Dev Disabil Res Rev 2009;15:193,199. [source] Reprogramming of genetic networks during initiation of the Fetal Alcohol Syndrome,DEVELOPMENTAL DYNAMICS, Issue 2 2007Maia L. Green Abstract Fetal Alcohol Spectrum Disorders (FASD) are birth defects that result from maternal alcohol use. We used a non a priori approach to prioritize candidate pathways during alcohol-induced teratogenicity in early mouse embryos. Two C57BL/6 substrains (B6J, B6N) served as the basis for study. Dosing pregnant dams with alcohol (2× 2.9 g/kg ethanol spaced 4 hr on day 8) induced FASD in B6J at a higher incidence than B6N embryos. Counter-exposure to PK11195 (4 mg/kg) significantly protected B6J embryos but slightly promoted FASD in B6N embryos. Microarray transcript profiling was performed on the embryonic headfold 3 hr after the first maternal alcohol injection (GEO data series accession GSE1074). This analysis revealed metabolic and cellular reprogramming that was substrain-specific and/or PK11195-dependent. Mapping ethanol-responsive KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways revealed down-regulation of ribosomal proteins and proteasome, and up-regulation of glycolysis and pentose phosphate pathway in B6N embryos; and significant up-regulation of tight junction, focal adhesion, adherens junction, and regulation of the actin cytoskeleton (and near-significant up-regulation of Wnt signaling and apoptosis) pathways in both substrains. Expression networks constructed computationally from these altered genes identified entry points for EtOH at several hubs (MAPK1, ALDH3A2, CD14, PFKM, TNFRSF1A, RPS6, IGF1, EGFR, PTEN) and for PK11195 at AKT1. Our findings are consistent with the growing view that developmental exposure to alcohol alters common signaling pathways linking receptor activation to cytoskeletal reorganization. The programmatic shift in cell motility and metabolic capacity further implies cell signals and responses that are integrated by the mitochondrial recognition site for PK11195. Developmental Dynamics 236:613,631, 2007. © 2007 Wiley-Liss, Inc. [source] Conceiving Risk, Bearing Responsibility: Fetal Alcohol Syndrome and the Diagnosis of Moral DisorderADDICTION, Issue 8 2004C. C. H. COOK No abstract is available for this article. [source] An fMRI Study of Number Processing in Children With Fetal Alcohol SyndromeALCOHOLISM, Issue 8 2010Ernesta M. Meintjes Background:, Number processing deficits are frequently seen in children exposed to alcohol in utero. Methods:, Functional magnetic resonance imaging was used to examine the neural correlates of number processing in 15 right-handed, 8- to 12-year-old children diagnosed with fetal alcohol syndrome (FAS) or partial FAS (PFAS) and 18 right-handed, age- and gender-matched controls from the Cape Coloured (mixed ancestry) community in Cape Town, South Africa, using Proximity Judgment and Exact Addition tasks. Results:, Control children activated the expected fronto-parietal network during both tasks, including the anterior horizontal intraparietal sulcus (HIPS), left posterior HIPS, left precentral sulcus, and posterior medial frontal cortex. By contrast, on the Proximity Judgment task, the exposed children recruited additional parietal pathways involving the right and left angular gyrus and posterior cingulate/precuneus, which may entail verbally mediated recitation of numbers and/or subtraction to assess relative numerical distances. During Exact Addition, the exposed children exhibited more diffuse and widespread activations, including the cerebellar vermis and cortex, which have been found to be activated in adults engaged in particularly challenging number processing problems. Conclusions:, The data suggest that, whereas control children rely primarily on the fronto-parietal network identified in previous studies to mediate number processing, children with FAS/PFAS recruit a broader range of brain regions to perform these relatively simple number processing tasks. Our results are consistent with structural neuroimaging findings indicating that the parietal lobe is relatively more affected by prenatal alcohol exposure and provide the first evidence for brain activation abnormalities during number processing in children with FAS/PFAS, effects that persist even after controlling statistically for group differences in total intracranial volume and IQ. [source] Sensory Processing and Adaptive Behavior Deficits of Children Across the Fetal Alcohol Spectrum Disorder ContinuumALCOHOLISM, Issue 6 2010Joshua L. Carr Background:, Prenatal alcohol exposure can have detrimental effects on a child's development of adaptive behaviors necessary for success in the areas of academic achievement, socialization, and self-care. Sensory processing abilities have been found to affect a child's ability to successfully perform adaptive behaviors. The current study explored whether significant differences in sensory processing abilities, adaptive behavior, and neurocognitive functioning are observed between children diagnosed with partial Fetal Alcohol Syndrome (pFAS), Alcohol-Related Neurodevelopmental Disorder (ARND), or children who were prenatally exposed to alcohol (PEA), but did not meet criteria for an FASD diagnosis. The influence of IQ on adaptive behavior as well as further exploration of the relationship between sensory processing and adaptive behavior deficits among these children was also examined. Methods:, A secondary analysis was conducted on some of the Short Sensory Profile (SSP) scores, Adaptive Behavior Assessment System,Second Edition (ABAS-II) scores, and Wechsler Intelligence Scale,Fourth Edition/Wechsler Preschool and Primary Scale of Intelligence,Third Edition (WISC- IV/WPPSI,III) scores of 46 children between 3 and 14 years of age with pFAS, ARND, or who were PEA. Results:, Greater sensory processing deficits were found in children with a diagnosis of pFAS and ARND compared to those in the PEA group. Children with an ARND diagnosis scored significantly worse on measures of adaptive behavior than the PEA group. Children with pFAS scored significantly lower than children with ARND or PEA on perceptual/performance IQ. No correlation was found between IQ scores and adaptive behaviors across the FASD diagnostic categories. A significant positive correlation was found between SSP and ABAS-II scores. Conclusions:, Regardless of the diagnosis received under the FASD umbrella, functional difficulties that could not be observed using traditional measures of intelligence were found, supporting guidelines that a broad range of standardized assessments be included when screening children for FASD. [source] Magnetic Resonance Microscopy Defines Ethanol-Induced Brain Abnormalities in Prenatal Mice: Effects of Acute Insult on Gestational Day 7ALCOHOLISM, Issue 1 2010Elizabeth A. Godin Background:, This magnetic resonance microscopy (MRM)-based report is the second in a series designed to illustrate the spectrum of craniofacial and central nervous system (CNS) dysmorphia resulting from single- and multiple-day maternal ethanol treatment. The study described in this report examined the consequences of ethanol exposure on gestational day (GD) 7 in mice, a time in development when gastrulation and neural plate development begins; corresponding to the mid- to late third week postfertilization in humans. Acute GD 7 ethanol exposure in mice has previously been shown to result in CNS defects consistent with holoprosencephaly (HPE) and craniofacial anomalies typical of those in Fetal Alcohol Syndrome (FAS). MRM has facilitated further definition of the range of GD 7 ethanol-induced defects. Methods:, C57Bl/6J female mice were intraperitoneally (i.p.) administered vehicle or 2 injections of 2.9 g/kg ethanol on day 7 of pregnancy. Stage-matched control and ethanol-exposed GD 17 fetuses selected for imaging were immersion fixed in a Bouins/Prohance solution. MRM was conducted at either 7.0 Tesla (T) or 9.4 T. Resulting 29 ,m isotropic spatial resolution scans were segmented and reconstructed to provide 3D images. Linear and volumetric brain measures, as well as morphological features, were compared for control and ethanol-exposed fetuses. Following MRM, selected specimens were processed for routine histology and light microscopic examination. Results:, Gestational day 7 ethanol exposure resulted in a spectrum of median facial and forebrain deficiencies, as expected. This range of abnormalities falls within the HPE spectrum; a spectrum for which facial dysmorphology is consistent with and typically is predictive of that of the forebrain. In addition, other defects including median facial cleft, cleft palate, micrognathia, pituitary agenesis, and third ventricular dilatation were identified. MRM analyses also revealed cerebral cortical dysplasia/heterotopias resulting from this acute, early insult and facilitated a subsequent focused histological investigation of these defects. Conclusions:, Individual MRM scans and 3D reconstructions of fetal mouse brains have facilitated demonstration of a broad range of GD 7 ethanol-induced morphological abnormality. These results, including the discovery of cerebral cortical heterotopias, elucidate the teratogenic potential of ethanol insult during the third week of human prenatal development. [source] The Effects of Fetal Alcohol Syndrome on Response Execution and Inhibition: An Event-Related Potential StudyALCOHOLISM, Issue 11 2009Matthew J. Burden Background:, Both executive function deficits and slower processing speed are characteristic of children with fetal alcohol exposure, but the temporal dynamics of neural activity underlying cognitive processing deficits in fetal alcohol spectrum disorder have rarely been studied. To this end, event-related potentials (ERPs) were used to examine the nature of alcohol-related effects on response inhibition by identifying differences in neural activation during task performance. Methods:, We recorded ERPs during a Go/No-go response inhibition task in 2 groups of children in Cape Town, South Africa (M age = 11.7 years; range = 10 to 13),one diagnosed with fetal alcohol syndrome (FAS) or partial FAS (FAS/PFAS; n = 7); the other, a control group whose mothers abstained or drank only minimally during pregnancy (n = 6). Children were instructed to press a "Go" response button to all letter stimuli presented except for the letter "X," the "No-go" stimulus, which occurred relatively infrequently. Results:, Task performance accuracy and reaction time did not differ between groups, but differences emerged for 3 ERP components,P2, N2, and P3. The FAS/PFAS group showed a slower latency to peak P2, suggesting less efficient processing of visual information at a relatively early stage (,200 ms after stimulus onset). Moreover, controls showed a larger P2 amplitude to Go versus No-go, indicating an early discrimination between conditions that was not seen in the FAS/PFAS group. Consistent with previous literature on tasks related to cognitive control, the control group showed a well-defined, larger N2 to No-go versus Go, which was not evident in the FAS/PFAS group. Both groups showed the expected larger P3 amplitude to No-go versus Go, but this condition difference persisted in a late slow wave for the FAS/PFAS group, suggesting increased cognitive effort. Conclusions:, The timing and amplitude differences in the ERP measures suggest that slower, less efficient processing characterizes the FAS/PFAS group during initial stimulus identification. Moreover, the exposed children showed less sharply defined components throughout the stimulus and response evaluation processes involved in successful response inhibition. Although both groups were able to inhibit their responses equally well, the level of neural activation in the children with FAS/PFAS was greater, suggesting more cognitive effort. The specific deficits in response inhibition processing at discrete stages of neural activation may have implications for understanding the nature of alcohol-related deficits in other cognitive domains as well. [source] A Metric of Maternal Prenatal Risk Drinking Predicts Neurobehavioral Outcomes in Preschool ChildrenALCOHOLISM, Issue 4 2009Lisa M. Chiodo Background:, Fetal Alcohol Spectrum Disorders (FASDs), including Fetal Alcohol Syndrome, continue to be high-incidence developmental disorders. Detection of patterns of maternal drinking that place fetuses at risk for these disorders is critical to diagnosis, treatment, and prevention, but is challenging and often insufficient during pregnancy. Various screens and measures have been used to identify maternal risk drinking but their ability to predict child outcome has been inconsistent. This study hypothesized that a metric of fetal "at-risk" alcohol exposure (ARAE) derived from several indicators of maternal self-reported drinking would predict alcohol-related neurobehavioral dysfunctions in children better than individual measures of maternal alcohol consumption alone. Methods:, Self-reported peri-conceptional and repeated maternal drinking during pregnancy were assessed with semi-structured interviews and standard screens, i.e., the CAGE, T-ACE, and MAST, in a prospective sample of 75 African-American mothers. Drinking volumes per beverage type were converted to standard quantity and frequency measures. From these individual measures and screening instruments, a simple dichotomous index of prenatal ARAE was defined and used to predict neurobehavioral outcomes in the 4- to 5-year-old offspring of these women. Study outcomes included IQ, attention, memory, visual-motor integration, fine motor skill, and behavior. Statistical analyses controlled for demographic and other potential confounders. Results:, The current "at-risk" drinking metric identified over 62% of the mothers as drinking at risk levels,23% more than the selection criterion identified,and outperformed all individual quantity and frequency consumption measures, including averages of weekly alcohol use and "binge" alcohol exposures (assessed as intake per drinking occasion), as well as an estimate of the Maternal Substance Abuse Checklist (Coles et al., 2000), in predicting prenatal alcohol-related cognitive and behavioral dysfunction in 4- to 5-year-old children. Conclusions:, A metric reflecting multiple indices of "at-risk" maternal alcohol drinking in pregnancy had greater utility in predicting various prenatal alcohol-related neurobehavioral dysfunction and deficits in children compared to individual measures of maternal self-reported alcohol consumption or a previous maternal substance abuse index. Assessing fetal risk drinking in pregnant women was improved by including multiple indicators of both alcohol consumption and alcohol-related consequences and, if appropriate practical applications are devised, may facilitate intervention by health care workers during pregnancy and potentially reduce the incidence or severity of FASDs. [source] Alcohol Consumption among Low-Income Pregnant LatinasALCOHOLISM, Issue 11 2005Christina D. Chambers Abstract: Background: Due to changing cultural norms, Latinas of childbearing age residing in the U.S. may be at increasing risk of drinking harmful levels of alcohol during pregnancy, and may also be unaware of the risks for Fetal Alcohol Spectrum Disorders associated with this behavior. We assessed the prevalence of alcohol consumption in a sample of low-income pregnant Latinas and examined risk factors for alcohol use in the periconceptional period. Methods: As part of a larger intervention trial, a cross-sectional in-home interview study was conducted among a sample of 100 pregnant low-income Latinas receiving services from the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) in San Diego County, California. Results: Fifty-seven percent of respondents indicated they were either life-time abstainers or had not consumed any alcohol in the periconceptional period. Forty-three percent reported some alcohol use in the three months prior to recognition of the current pregnancy, and 20% reported at least one binge episode of four or more standard drinks during that time frame. Five percent reported drinking seven or more drinks per week, and 8% continued drinking alcohol after recognition of pregnancy. Significant predictors of any alcohol use in the periconceptional period included English language/higher level of acculturation, younger maternal age, lower parity, higher level of education, younger age at first drink, and having ever smoked. Women who were aware of alcohol warning messages and /or had more knowledge of the Fetal Alcohol Syndrome (FAS) were significantly more likely to have consumed alcohol in the periconceptional period. Frequency of periconceptional use of alcohol did not differ between women who planned or did not plan the pregnancy. Conclusion: The prevalence and pattern of early pregnancy alcohol consumption in this sample of Latinas is similar to patterns noted in other race/ethnic groups in the U.S. Level of knowledge about FAS and awareness of warning messages was not protective for early pregnancy alcohol consumption, suggesting that specific knowledge was insufficient to prevent exposure or that other factors reinforce maintenance of alcohol consumption in early pregnancy. Selective interventions in low-income Latinas are warranted, and should be focused on women of reproductive age who are binge or frequent drinkers and who are at risk of becoming pregnant. [source] Fetal Alcohol Spectrum,The Hidden Epidemic in Our CourtsJUVENILE AND FAMILY COURT JOURNAL, Issue 4 2001KATHRYN PAGE PH.D. ABSTRACT This article discusses the basics of Fetal Alcohol Syndrome and Fetal Alcohol Effects (FAS/E): the history, nature, prevalence, causes, and effects of prenatal exposure to alcohol. Some of the unique features of FAS/E are explored, particularly those that make it so hard to spot and those that predispose people to nonproductive or criminal activity. The presentation of FAS/E in Juvenile Court is discussed and put in the context of the multiplicity of factors pertaining to delinquency; finally, innovative interventions, approaches and resources are laid out. Issues surrounding FAS/E as they appear in Family Court are then explored, with emphasis on the intergenerational transmission of this array of conditions and how we might interrupt such transmission. [source] Fetal alcohol syndrome (FAS) in C57BL/6 mice detected through proteomics screening of the amniotic fluid,BIRTH DEFECTS RESEARCH, Issue 4 2008Susmita Datta Abstract BACKGROUND: Fetal Alcohol Syndrome (FAS), a severe consequence of the Fetal Alcohol Spectrum Disorders, is associated with craniofacial defects, mental retardation, and stunted growth. Previous studies in C57BL/6J and C57BL/6N mice provide evidence that alcohol-induced pathogenesis follows early changes in gene expression within specific molecular pathways in the embryonic headfold. Whereas the former (B6J) pregnancies carry a high-risk for dysmorphogenesis following maternal exposure to 2.9 g/kg alcohol (two injections spaced 4.0 h apart on gestation day 8), the latter (B6N) pregnancies carry a low-risk for malformations. The present study used this murine model to screen amniotic fluid for biomarkers that could potentially discriminate between FAS-positive and FAS-negative pregnancies. METHODS: B6J and B6N litters were treated with alcohol (exposed) or saline (control) on day 8 of gestation. Amniotic fluid aspirated on day 17 (n = 6 replicate litters per group) was subjected to trypsin digestion for analysis by matrix-assisted laser desorption,time of flight mass spectrometry with the aid of denoising algorithms, statistical testing, and classification methods. RESULTS: We identified several peaks in the proteomics screen that were reduced consistently and specifically in exposed B6J litters. Preliminary characterization by liquid chromatography tandem mass spectrometry and multidimensional protein identification mapped the reduced peaks to alpha fetoprotein (AFP). The predictive strength of AFP deficiency as a biomarker for FAS-positive litters was confirmed by area under the receiver operating characteristic curve. CONCLUSIONS: These findings in genetically susceptible mice support clinical observations in maternal serum that implicate a decrease in AFP levels following prenatal alcohol damage. Birth Defects Research (Part A), 2008. © 2008 Wiley-Liss, Inc. [source] Fetal alcohol syndrome through the eyes of parentsADDICTION BIOLOGY, Issue 2 2004Jocie DeVries Although fetal alcohol syndrome (FAS) was first identified by research scientists in the USA in 1973, it was not until 1989 when an adoptive parent, Michael Dorris, wrote The Broken Cord, that a practical description of the disability came into public awareness. Within the next 2 years, parents of children diagnosed with this disability teemed up with interested professionals to organize the FAS Family Resource Institute (FAS*FRI). This educational non-profit organization has now devoted over a decade to their mission to identify, understand and care for individuals with fetal alcohol syndrome/effects (FAS/E) and to prevent this disability from occurring in future generations. Their mission has necessitated the identification of a behavioral phenotype for FAS/E, the development of a professional training curriculum, and operation of a national family advocacy and mentoring network. By adding their own families' experiences to the information gathered from thousands of other families with diagnosed children, they have accumulated enough experiential, frontline reports which are similar enough to serve as their research science base. [source] Commentary on ,Fetal alcohol syndrome in the corrections system' by L. Burd et al.ADDICTION BIOLOGY, Issue 2 2004Heidi Heitkamp [source] Effects of Ethanol on Mouse Embryonic Stem CellsALCOHOLISM, Issue 12 2009Alla Arzumanyan Background:, Fetal alcohol syndrome (FAS) reflects a constellation of congenital abnormalities caused by excess maternal consumption of alcohol. It is likely that interference with embryonic development plays a role in the pathogenesis of the disorder. Ethanol-induced apoptosis has been suggested as a causal factor in the genesis of FAS. Mouse embryonic stem (mES) cells are pluripotent cells that differentiate in vitro to cell aggregates termed embryoid bodies (EBs), wherein differentiation capacity and gene expression profile are similar to those of the early embryo. Methods:, To investigate the effects of ethanol during differentiation, mES cells were cultured on a gelatin surface in the presence of leukemia inhibitory factor which maintains adherent undifferentiated cells or in suspension to promote formation of EBs. All cells were treated (1,6 days) with 80 mM ethanol. The pluripotency and differentiation of mES cells were evaluated by western blotting of stage-specific embryonic antigen (SSEA-1), transcription factors Oct-3/4, Sox-2, and Nanog, using alkaline phosphatase staining. Apoptosis (early to late stages) was assessed by fluorescence-activated cell sorting using TdT-mediated biotin,dUTP nick-end labelling assay and fluorescein isothiocyanate-Annexin V/propidium iodide staining. Results:, Ethanol increased apoptosis during in vitro differentiation of mES cells to EBs, whereas undifferentiated cells were not affected. Ethanol exposure also interfered with pluripotency marker patterns causing an upregulation of SSEA-1 under self-renewal conditions. In EBs, ethanol delayed the downregulation of SSEA-1 and affected the regulation of transcription factors during differentiation. Conclusion:, Our findings suggest that ethanol may contribute to the pathogenesis of FAS by triggering apoptotic pathways during differentiation of embryonic stem cells and deregulating early stages of embryogenesis. [source] Socio-cognitive Habilitation Using the Math Interactive Learning Experience Program for Alcohol-Affected ChildrenALCOHOLISM, Issue 8 2007Julie A. Kable Background: Fetal alcohol syndrome (FAS) has been recognized as a disabling condition with a significant impact on the neurobehavioral functioning of affected individuals, including cognition, behavior, and academic functioning, but little research has been performed on targeted interventions for these children. Methods: A socio-cognitive habilitative program focused on improving behavior and math functioning in children 3 to 10 years of age (n=61) was developed and evaluated. The intervention provided parental instruction on FAS, advocacy, and behavioral regulation via workshops and interactive math tutoring with children. All families received parental instruction and were then randomly assigned to either the math instruction or standard psychoeducational care groups. Results: Satisfaction with workshops was very high, with over 90% agreeing that trainers were knowledgeable and materials easy to understand and helpful. Significant gains in knowledge were found for information provided in the instructional groups. At posttesting, caregivers reported fewer problem behaviors on the Achenbach Child Behavior Checklist, Internalizing Problem Behavior, Externalizing Problem Behavior, and Total Problem Behavior summary scales. After 5 months, both groups of children demonstrated gains in math knowledge but significantly higher gains were found in the group receiving direct math instruction. The math treatment group was also more likely to demonstrate a gain of over 1 standard deviation on any of the 4 math outcome measures used. Conclusions: These findings suggest that parents of children with fetal alcohol spectrum disorders (FAS(D)) benefit from instruction in understanding their child's alcohol-related neurological damage and strategies to provide positive behavioral supports and that targeted psychoeducational programs may be able to remediate some of the math deficits associated with prenatal alcohol exposure. [source] Fetal alcohol syndrome and developing craniofacial and dental structures , a reviewORTHODONTICS & CRANIOFACIAL RESEARCH, Issue 4 2006LB Sant'Anna Structured abstract Authors ,, Sant'Anna LB, Tosello DO Objectives ,, Fetal alcohol syndrome (FAS) is a collection of signs and symptoms seen in children exposed to alcohol in the prenatal period. It is characterized mainly by a distinct pattern of craniofacial malformations, physical and mental retardation. However, with the increased incidence of FAS, there is a great variation in the clinical features of FAS. Design ,, Narrative review. Results ,, This review describes data from clinical and experimental studies, and in vitro models. Experimental studies have shown that alcohol has a direct toxic effect on the ectodermal and mesodermal cells of the developing embryo, particularly in the cells destined to give rise to dentofacial structures (i.e. cranial neural crest cells). Other effects, such as, abnormal pattern of cranial and mandibular growth and altered odontogenesis are described in detail. The exact mechanism by which alcohol induces its teratogenic effects remains still unknown. The possible mechanisms are outlined here, with an emphasis on the developing face and tooth. Possible future research directions and treatment strategies are also discussed. Conclusion ,, Early identification of children affected by prenatal alcohol exposure leads to interventions, services, and improved outcomes. FAS can be prevented with the elimination of alcohol consumption during pregnancy. We need to provide education, target high-risk groups, and make this issue a high priority in terms of public health. [source] Fetal alcohol syndrome (FAS) in C57BL/6 mice detected through proteomics screening of the amniotic fluid,BIRTH DEFECTS RESEARCH, Issue 4 2008Susmita Datta Abstract BACKGROUND: Fetal Alcohol Syndrome (FAS), a severe consequence of the Fetal Alcohol Spectrum Disorders, is associated with craniofacial defects, mental retardation, and stunted growth. Previous studies in C57BL/6J and C57BL/6N mice provide evidence that alcohol-induced pathogenesis follows early changes in gene expression within specific molecular pathways in the embryonic headfold. Whereas the former (B6J) pregnancies carry a high-risk for dysmorphogenesis following maternal exposure to 2.9 g/kg alcohol (two injections spaced 4.0 h apart on gestation day 8), the latter (B6N) pregnancies carry a low-risk for malformations. The present study used this murine model to screen amniotic fluid for biomarkers that could potentially discriminate between FAS-positive and FAS-negative pregnancies. METHODS: B6J and B6N litters were treated with alcohol (exposed) or saline (control) on day 8 of gestation. Amniotic fluid aspirated on day 17 (n = 6 replicate litters per group) was subjected to trypsin digestion for analysis by matrix-assisted laser desorption,time of flight mass spectrometry with the aid of denoising algorithms, statistical testing, and classification methods. RESULTS: We identified several peaks in the proteomics screen that were reduced consistently and specifically in exposed B6J litters. Preliminary characterization by liquid chromatography tandem mass spectrometry and multidimensional protein identification mapped the reduced peaks to alpha fetoprotein (AFP). The predictive strength of AFP deficiency as a biomarker for FAS-positive litters was confirmed by area under the receiver operating characteristic curve. CONCLUSIONS: These findings in genetically susceptible mice support clinical observations in maternal serum that implicate a decrease in AFP levels following prenatal alcohol damage. Birth Defects Research (Part A), 2008. © 2008 Wiley-Liss, Inc. [source] Relationships between ophthalmological and neuropaediatric findings in children adopted from Eastern EuropeACTA OPHTHALMOLOGICA, Issue 2 2010Marita Andersson Grönlund Abstract. Purpose:, This study aimed to evaluate and relate visual function, ocular dimensions and neuropaediatric findings in adoptees from Eastern Europe. Methods:, We studied 72 of 99 children, born during 1990,95 and adopted from Eastern Europe to western Sweden during 1993,97. The children (mean age 7.5 years, range 4.8,10.5 years; 41 boys, 31 girls) were examined after a mean period of 5 years post-adoption by a multidisciplinary team. Correlations between ophthalmological findings and neuropaediatric data were analysed. Results:, Bivariate and regression analyses indicate a significant positive correlation between visual acuity (VA) and perceptual organization (p < 0.001), as well as between strabismus and verbal comprehension (p < 0.02). Fetal alcohol syndrome (FAS) was correlated with low VA (p < 0.02), subnormal stereovision (p < 0.009) and small optic discs (p < 0.02). Small head circumference was related to low VA (p < 0.015) and small optic discs (p < 0.03). Furthermore, small optic discs were related to low birthweight (p < 0.005) and preterm birth (p < 0.01). Large optic cups were correlated with poorer perceptual organization (p < 0.02). Conclusions:, In this group of adoptees from Eastern Europe, ophthalmological findings were correlated to neuropaediatric findings, especially those arising from prenatal adverse events resulting in growth deficiency and central nervous system damage. Therefore, it is important and valuable with an ophthalmological examination in children adopted from Eastern Europe. [source] Ethanol neurotoxicity and dentate gyrus developmentCONGENITAL ANOMALIES, Issue 3 2008Takanori Miki ABSTRACT Maternal alcohol ingestion during pregnancy adversely affects the developing fetus, often leading to fetal alcohol syndrome (FAS). One of the most severe consequences of FAS is brain damage that is manifested as cognitive, learning, and behavioral deficits. The hippocampus plays a crucial role in such abilities; it is also known as one of the brain regions most vulnerable to ethanol-induced neurotoxicity. Our recent studies using morphometric techniques have further shown that ethanol neurotoxicity appears to affect the development of the dentate gyrus in a region-specific manner; it was found that early postnatal ethanol exposure causes a transitory deficit in the hilus volume of the dentate gyrus. It is strongly speculated that such structural modifications, even transitory ones, appear to result in developmental abnormalities in the brain circuitry and lead to the learning disabilities observed in FAS children. Based on reports on possible factors deciding ethanol neurotoxicity to the brain, we review developmental neurotoxicity to the dentate gyrus of the hippocampal formation. [source] Prevalence and epidemiologic characteristics of FASD from various research methods with an emphasis on recent in-school studiesDEVELOPMENTAL DISABILITIES RESEARCH REVIEW, Issue 3 2009Philip A. May Abstract Researching the epidemiology and estimating the prevalence of fetal alcohol syndrome (FAS) and other fetal alcohol spectrum disorders (FASD) for mainstream populations anywhere in the world has presented a challenge to researchers. Three major approaches have been used in the past: surveillance and record review systems, clinic-based studies, and active case ascertainment methods. The literature on each of these methods is reviewed citing the strengths, weaknesses, prevalence results, and other practical considerations for each method. Previous conclusions about the prevalence of FAS and total FASD in the United States (US) population are summarized. Active approaches which provide clinical outreach, recruitment, and diagnostic services in specific populations have been demonstrated to produce the highest prevalence estimates. We then describe and review studies utilizing in-school screening and diagnosis, a special type of active case ascertainment. Selected results from a number of in-school studies in South Africa, Italy, and the US are highlighted. The particular focus of the review is on the nature of the data produced from in-school methods and the specific prevalence rates of FAS and total FASD which have emanated from them. We conclude that FAS and other FASD are more prevalent in school populations, and therefore the general population, than previously estimated. We believe that the prevalence of FAS in typical, mixed-racial, and mixed-socioeconomic populations of the US is at least 2 to 7 per 1,000. Regarding all levels of FASD, we estimate that the current prevalence of FASD in populations of younger school children may be as high as 2,5% in the US and some Western European countries. © 2009 Wiley-Liss, Inc. Dev Disabil Res Rev 2009; 15:176,192. [source] Brain dysmorphology in individuals with severe prenatal alcohol exposureDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 3 2001Sarah L Archibald MA Our previous studies revealed abnormalities on structural MRI (sMRI) in small groups of children exposed to alcohol prenatally. Microcephaly, disproportionately reduced basal ganglia volume, and abnormalities of the cerebellar vermis and corpus callosum were demonstrated. The present study used sMRI to examine in detail the regional pattern of brain hypoplasia resulting from prenatal exposure to alcohol using a higher resolution imaging protocol and larger sample sizes than reported previously. Fourteen participants (mean 11.4 years; eight females, six males) with fetal alcohol syndrome (FAS) and 12 participants (mean 14.8 years; four females, eight males) with prenatal exposure to alcohol (PEA) but without the facial features of FAS were compared to a group of 41 control participants (mean 12.8 years, 20 females, 21 males). Findings of significant microcephaly and disproportionately reduced basal ganglia volumes in the FAS group were confirmed. Novel findings were that in FAS participants, white matter volumes were more affected than gray matter volumes in the cerebrum, and parietal lobes were more affected than temporal and occipital lobes. Among subcortical structures, in contrast to the disproportionate effects on caudate nucleus, the hippocampus was relatively preserved in FAS participants. Differences between the PEA group and controls were generally non-significant; however, among a few of the structures most affected in FAS participants, there was some evidence for volume reduction in PEA participants as well, specifically in basal ganglia and the parietal lobe. There were no group differences in cerebral volume asymmetries. Severe prenatal alcohol exposure appears to produce a specific pattern of brain hypoplasia. [source] Advantages of mixed effects models over traditional ANOVA models in developmental studies: A worked example in a mouse model of fetal alcohol syndromeDEVELOPMENTAL PSYCHOBIOLOGY, Issue 7 2007Patricia E. Wainwright Abstract Developmental studies in animals often violate the assumption of statistical independence of observations due to the hierarchical nature of the data (i.e., pups cluster by litter, correlation of individual observations over time). Mixed effect modeling (MEM) provides a robust analytical approach for addressing problems associated with hierarchical data. This article compares the application of MEM to traditional ANOVA models within the context of a developmental study of prenatal ethanol exposure in mice. The results of the MEM analyses supported the ANOVA results in showing that a large proportion of the variability in both behavioral score and brain weight could be explained by ethanol. The MEM also identified that there were significant interactions between ethanol and litter size in relation to behavioral scores and brain weight. In addition, the longitudinal modeling approach using linear MEM allowed us to model for flexible weight gain over time, as well as to provide precise estimates of these effects, which would be difficult in repeated measures ANOVA. © 2007 Wiley Periodicals, Inc. Dev Psychobiol 49: 664,674, 2007. [source] The relation between different dimensions of alcohol consumption and burden of disease: an overviewADDICTION, Issue 5 2010Jürgen Rehm ABSTRACT Aims As part of a larger study to estimate the global burden of disease and injury attributable to alcohol: to evaluate the evidence for a causal impact of average volume of alcohol consumption and pattern of drinking on diseases and injuries; to quantify relationships identified as causal based on published meta-analyses; to separate the impact on mortality versus morbidity where possible; and to assess the impact of the quality of alcohol on burden of disease. Methods Systematic literature reviews were used to identify alcohol-related diseases, birth complications and injuries using standard epidemiological criteria to determine causality. The extent of the risk relations was taken from meta-analyses. Results Evidence of a causal impact of average volume of alcohol consumption was found for the following major diseases: tuberculosis, mouth, nasopharynx, other pharynx and oropharynx cancer, oesophageal cancer, colon and rectum cancer, liver cancer, female breast cancer, diabetes mellitus, alcohol use disorders, unipolar depressive disorders, epilepsy, hypertensive heart disease, ischaemic heart disease (IHD), ischaemic and haemorrhagic stroke, conduction disorders and other dysrhythmias, lower respiratory infections (pneumonia), cirrhosis of the liver, preterm birth complications and fetal alcohol syndrome. Dose,response relationships could be quantified for all disease categories except for depressive disorders, with the relative risk increasing with increased level of alcohol consumption for most diseases. Both average volume and drinking pattern were linked causally to IHD, fetal alcohol syndrome and unintentional and intentional injuries. For IHD, ischaemic stroke and diabetes mellitus beneficial effects were observed for patterns of light to moderate drinking without heavy drinking occasions (as defined by 60+ g pure alcohol per day). For several disease and injury categories, the effects were stronger on mortality compared to morbidity. There was insufficient evidence to establish whether quality of alcohol had a major impact on disease burden. Conclusions Overall, these findings indicate that alcohol impacts many disease outcomes causally, both chronic and acute, and injuries. In addition, a pattern of heavy episodic drinking increases risk for some disease and all injury outcomes. Future studies need to address a number of methodological issues, especially the differential role of average volume versus drinking pattern, in order to obtain more accurate risk estimates and to understand more clearly the nature of alcohol,disease relationships. [source] Fetal alcohol syndrome through the eyes of parentsADDICTION BIOLOGY, Issue 2 2004Jocie DeVries Although fetal alcohol syndrome (FAS) was first identified by research scientists in the USA in 1973, it was not until 1989 when an adoptive parent, Michael Dorris, wrote The Broken Cord, that a practical description of the disability came into public awareness. Within the next 2 years, parents of children diagnosed with this disability teemed up with interested professionals to organize the FAS Family Resource Institute (FAS*FRI). This educational non-profit organization has now devoted over a decade to their mission to identify, understand and care for individuals with fetal alcohol syndrome/effects (FAS/E) and to prevent this disability from occurring in future generations. Their mission has necessitated the identification of a behavioral phenotype for FAS/E, the development of a professional training curriculum, and operation of a national family advocacy and mentoring network. By adding their own families' experiences to the information gathered from thousands of other families with diagnosed children, they have accumulated enough experiential, frontline reports which are similar enough to serve as their research science base. [source] Paternal contribution to fetal alcohol syndromeADDICTION BIOLOGY, Issue 2 2004Ernest Abel Maternal alcohol use during pregnancy is associated with a wide range of adverse outcomes for the child. Many women who drink during pregnancy also have male partners who abuse alcohol. Existing data on paternal effects of alcohol abuse during the preconceptual period and at the time of conception are reviewed. Epidemiological data offer some support for a paternal influence on birth weight, congenital heart defects, and some evidence of mild cognitive impairments. Animal data have demonstrated decreased litter size, increased prevalence of low birth weight fetuses and mixed data on risk of malformations. Increased susceptibility to Pseudomonas bacterial infection has been reported. Cognitive and behavioral findings are the most robust effects. These include learning and memory deficits, hyperactivity, and poor stress tolerance. Multiple causal mechanisms for a paternal effect have been suggested, but none seems satisfactory to explain all findings. Further research is needed on paternal effects in animals and human populations. The results of this research may influence prevention activities. [source] Increased sibling mortality in children with fetal alcohol syndromeADDICTION BIOLOGY, Issue 2 2004Larry Burd We compared the rate of all-cause mortality in siblings of children diagnosed with fetal alcohol syndrome (FAS) with the siblings of matched controls. The siblings of children with FAS had increased mortality (11.4%) compared with matched controls (2.0%), a 530% increase in mortality. The age of death in case siblings deaths occurred later (between 1 day and 7 years) compared with the controls (1 day to 4 years) [odds ratio (OR),=,2.4 (0.4,-,15.6)]. Siblings of children with FAS had increased risk of death due to infectious illness [OR,=,13.7 (1.2,-,361)] and sudden infant death syndrome compared with controls [OR,=,10.2 (1.2,-,75.1)]. A diagnosis of FAS is an important risk marker for mortality in the siblings of the proband even if they do not have FAS. Maternal alcoholism appears to be a useful risk marker for increased mortality risk in diagnosed cases and their siblings. This has important implications in the management of family members of children with FAS. [source] Screening for fetal alcohol syndrome: is it feasible and necessary?ADDICTION BIOLOGY, Issue 2 2000Larry Burd The potential to utilize screening strategies to improve the identification and outcome of persons with fetal alcohol syndrome (FAS) is reviewed. FAS is a condition where screening and surveillance activities would be appropriate. Development of FAS screening and surveillance programs is encouraged because the disorder is expensive. People with FAS have poor outcomes as adults with less than 10% living independently. Several useful tools and models are available. Screening would improve ascertainment and prevalence estimates. Early identification could improve access to services and long term outcome, secondary disabilities and, by extension, excess disability in affected children could be decreased. Lastly, mothers who are at the highest risk to have additional children with FAS could be identified and offered treatment. While both screening and surveillance activities are discussed, the principle focus of this article is a review of the screening process. Two screening tools and several screening methodologies for FAS are available. Since no test will be appropriate in all settings, screening tests need to be selected depending on the setting and population of interest. Screening for FAS should be conducted in a variety of settings and in populations of both high and moderate risk. The results would also provide important data to influence public policy development and resource allocation. Appropriate evaluation of the efficacy, efficiency and effectiveness of FAS screening tools and methodologies would be important before utilization in screening programs. [source] Infant Symbolic Play as an Early Indicator of Fetal Alcohol-Related DeficitINFANCY, Issue 6 2010Christopher D. Molteno Infant symbolic play was examined in relation to prenatal alcohol exposure and socioenvironmental background and to predict which infants met criteria for fetal alcohol syndrome (FAS) at 5 years. A total of 107 Cape-Colored, South African infants born to heavy drinking mothers and abstainers/light drinkers were recruited prenatally. Complexity of play, sociodemographic and psychological correlates of maternal alcohol use, and quality of parenting were assessed at 13 months, and intelligence quotient and FAS diagnosis at 5 years. The effect of drinking on spontaneous play was not significant after control for social environment. In contrast, prenatal alcohol and quality of parenting related independently to elicited play. Elicited play predicted 5-year Digit Span and was poorer in infants subsequently diagnosed with FAS/partial FAS and in nonsyndromal heavily exposed infants, compared with abstainers/light drinkers. Thus, symbolic play may provide an early indicator of risk for alcohol-related deficits. The independent effects of prenatal alcohol and quality of parenting suggest that infants whose symbolic play is adversely affected by alcohol exposure may benefit from stimulation from a responsive caregiver. [source] Functions and pathophysiological roles of phospholipase D in the brainJOURNAL OF NEUROCHEMISTRY, Issue 6 2005Jochen Klein Abstract Ten years after the isoforms of mammalian phospholipase D (PLD), PLD1 and 2, were cloned, their roles in the brain remain speculative but several lines of evidence now implicate these enzymes in basic cell functions such as vesicular trafficking as well as in brain development. Many mitogenic factors, including neurotransmitters and growth factors, activate PLD in neurons and astrocytes. Activation of PLD downstream of protein kinase C seems to be a required step for astroglial proliferation. The characteristic disruption of the PLD signaling pathway by ethanol probably contributes to the delay of brain growth in fetal alcohol syndrome. The post-natal increase of PLD activities concurs with synapto- and myelinogenesis in the brain and PLD is apparently involved in neurite formation. In the adult and aging brain, PLD activity has antiapoptotic properties suppressing ceramide formation. Increased PLD activities in acute and chronic neurodegeneration as well as in inflammatory processes are evidently due to astrogliosis and may be associated with protective responses of tissue repair and remodeling. ARF-regulated PLD participates in receptor endocytosis as well as in exocytosis of neurotransmitters where PLD seems to favor vesicle fusion by modifications of the shape and charge of lipid membranes. Finally, PLD activities contribute free choline for the synthesis of acetylcholine in the brain. Novel tools such as RNA interference should help to further elucidate the roles of PLD isoforms in brain physiology and pathology. [source] | ||||||||||||||||