Although the hazards of prenatal exposure to addictive substances have been documented for decades, it continues to be a prevalent social and health concern today. Alcohol and cocaine are two commonly abused substances during pregnancy, often leading to behavioral and cognitive disorders in exposed children. At present, the relationship between teratogenic effects of prenatal alcohol exposure (PAE) and prenatal cocaine exposure (PCE) on the brain and observed behavioral outcomes is still unclear. A primary reason for this incomplete understanding is the lack of information regarding neuronal functioning in these populations. Functional MRI, which measures real-time brain activation in response to certain stimuli, can be utilized to bridge the gap between known structural damage and observed behavioral outcomes. This thesis aims to examine structural and functional alterations in PAE and PCE populations as compared to unexposed, socio-economic status-matched populations. As the PAE population is highly affected by structural dysmorphology, the applicability of a newly developed diffeomorphic image registration method to this population is examined. Additionally, task-positive and task-negative functional connectivity and activity are investigated in the PAE population, and related to underlying structural alterations. Neural correlates of global arousal and emotional regulation are investigated in the PCE population, as these behavioral outcomes are most notable. Similarly, functional connectivity and activation in task-positive and task-negative networks, as well as correlated structural measures, are examined in the PCE population. The diffeomorphic image registration algorithm was found to improve both structural and functional image registration for the PAE population. In the examination of specific deficits in arithmetic processing, poorer performance in the PAE group was attributed to a multi-level effect produced by altered structural and functional connectivity and functional activity in calculation and default mode networks. Baseline arousal levels were found to be higher in adolescents with PCE as compared to healthy controls (by altered default mode network functioning); emotional regulation also appeared to be affected in the PCE group by a prefrontal-amygdala structural and functional disconnect. The findings of this thesis give insights into the relationship between task-positive and task-negative duality and cognitive impairment, and contribute to a more comprehensive understanding of the spectrum of clinical disorders caused by prenatal exposure to alcohol and cocaine.

Diagnosis of fetal alcohol spectrum disorders (FASD) is challenging and typically requires confirmation of in utero alcohol exposure. Due to the poor reliability of maternal self-reports, biomarkers have emerged to address the problem of obtaining exposure history. A relatively novel method for detecting prenatal alcohol exposure is analysis of meconium for fatty acid ethyl esters (FAEEs), which are non-oxidative ethanol metabolites. Screening newborns using meconium FAEEs may facilitate early diagnosis and intervention in alcohol-affected individuals. The overall objective of this thesis is to further investigate, validate, and assess the clinical utility of meconium FAEE analysis as a screening tool for the identification of neonates at-risk for FASD. This objective was addressed in four separate studies. The first study assessed whether meconium FAEE concentrations can be predictive of ethanol-induced organ injury in fetal sheep, and determined that the levels of these esters could be used to identify fetuses at-risk for organ dysfunction that do not display overt physical signs of ethanol teratogenicity. The second study investigated the effect of delayed meconium collection and contamination with postnatal stool on FAEE analysis, and determined it to be a risk factor for false positive test results. In the third study, maternal willingness to partake in an open meconium screening program was assessed and found to be low enough to diminish the utility of meconium FAEE testing for population-based open screening. Lastly, a systematic review examining the capacity for FAEE synthesis and the enzymology of this non-oxidative metabolic pathway in mammalian organs and tissues revealed that FAEE synthesis is mediated by numerous enzymes and isoenzymes, many of which have other primary physiological functions, and that their contribution to overall FAEE-synthesis may be tissue-specific. Overall, the results of this research provide new information on the benefits, limitations, and utility of meconium FAEE testing as a screening tool for identifying prenatal alcohol exposure − a test that may be of great clinical value in the diagnosis and management of FASD.

Diagnosis of fetal alcohol spectrum disorders (FASD) is challenging and typically requires confirmation of in utero alcohol exposure. Due to the poor reliability of maternal self-reports, biomarkers have emerged to address the problem of obtaining exposure history. A relatively novel method for detecting prenatal alcohol exposure is analysis of meconium for fatty acid ethyl esters (FAEEs), which are non-oxidative ethanol metabolites. Screening newborns using meconium FAEEs may facilitate early diagnosis and intervention in alcohol-affected individuals. The overall objective of this thesis is to further investigate, validate, and assess the clinical utility of meconium FAEE analysis as a screening tool for the identification of neonates at-risk for FASD. This objective was addressed in four separate studies. The first study assessed whether meconium FAEE concentrations can be predictive of ethanol-induced organ injury in fetal sheep, and determined that the levels of these esters could be used to identify fetuses at-risk for organ dysfunction that do not display overt physical signs of ethanol teratogenicity. The second study investigated the effect of delayed meconium collection and contamination with postnatal stool on FAEE analysis, and determined it to be a risk factor for false positive test results. In the third study, maternal willingness to partake in an open meconium screening program was assessed and found to be low enough to diminish the utility of meconium FAEE testing for population-based open screening. Lastly, a systematic review examining the capacity for FAEE synthesis and the enzymology of this non-oxidative metabolic pathway in mammalian organs and tissues revealed that FAEE synthesis is mediated by numerous enzymes and isoenzymes, many of which have other primary physiological functions, and that their contribution to overall FAEE-synthesis may be tissue-specific. Overall, the results of this research provide new information on the benefits, limitations, and utility of meconium FAEE testing as a screening tool for identifying prenatal alcohol exposure − a test that may be of great clinical value in the diagnosis and management of FASD.

Thesis (M.A.) - Carleton University, 2008. / Includes bibliographical references (p. 128-139). Also available in electronic format on the Internet.

Over the past decade, the "problem" of Fetal Alcohol Syndrome and Fetal Alcohol Effects among Aboriginal peoples has received increasing attention from the Canadian nation-state. However, few feminist, anti-racist, anti-ableist, and anti-colonial scholars have offered a critique of FAS/E "prevention" policies aimed at Aboriginal women. In this dissertation, I present my analysis of the "official knowledge" and "public pedagogies" articulated in one such policy, The First Nations and Inuit Fetal Alcohol Syndrome/ Fetal Alcohol Effects Initiative (herein "the Initiative"). This analysis unravels the complex and contradictory tensions in contemporary state policy formation. My findings show how the Initiative paradoxically supports the development of inclusive, grassroots approaches to FAS/E prevention in Aboriginal communities while at the same time eclipsing the voices and concerns of Aboriginal women. Though neglected in the official policy texts and talk of the Initiative, young Aboriginal mothers' agency and insights are central in the dialectic of ideology, discourse, and lived experience that this study documents. To facilitate this shift, I engage a productive methodological synthesis of textual analysis, institutional ethnography, and participatory research, by grounding my analysis of the texts in indepth group interviews with six Aboriginal mothers whose lives include substance use and FAS/E. This study offers significant implications for the development of future policy, research, and "culturally appropriate" pedagogy for and about FAS/E "prevention". My findings do not support the outright rejection of medical models of disability, as has been favoured by many critical theorists and activists on the grounds that such models are universally oppressive and disenfranchising. Rather, the women's insights into their own lived experiences emphasize the simultaneously enabling and disabling consequences of medicalization. Accordingly, my findings underscore the urgent need to reconsider the roles of "race", gender, class, nation and dis/ability in contemporary theories and practices of substantive citizenship and nation-building in and outside of education. / Education, Faculty of / Educational Studies (EDST), Department of / Graduate

Indiana University-Purdue University Indianapolis (IUPUI) / Fetal alcohol spectrum disorder is a disease caused by prenatal alcohol exposure. It is characterized by craniofacial abnormalities, growth retardation, central nervous system defects, learning disabilities and a variety of other minor defects. Even though it affects 2-5% of individuals born every year, very little is known about the mechanisms that cause it. The zebrafish (Danio rerio) presents as an interesting and efficient model for studying this disease. This study provides some insight into the mechanisms underlying observed FASD phenotypes and, more specifically, the transcription factor elf3, which is downregulated in response to ethanol exposure during early embryonic development. Here we show a number of elf3 target genes that are downregulated during early development in response to ethanol exposure. We also give some insight into the expression pattern of elf3 in relation to zygotic genome activation. Translation blocking morpholino oligonucleotides were used to implicate Elf3 in epiboly movements during gastrulation and zebrafish tail development. Taken together these results help to strengthen the zebrafish as a model for FASD in addition to giving greater insight into both the expression pattern and role of Elf3 during development.

Thesis (Ph.D.)--University of Toronto, 2004. / Adviser: Joanne Rovet.

Background: Prevalence and characteristics of fetal alcohol syndrome (FAS) and total fetal alcohol spectrum disorders (FASD) were studied in a second sample of three South African rural communities to assess change. Methods: Active case ascertainment focused on children with height, weight and/or head circumference <= 25th centile and randomly-selected children. Final diagnoses were based on dysmorphology, neurobehavioral scores, and maternal risk interviews. Results: Cardinal facial features, head circumference, and total dysmorphology scores differentiated specific FASD diagnostic categories in a somewhat linear fashion but all FASD traits were significantly worse than those of randomly-selected controls. Neurodevelopmental delays were significantly worse for children with FASD than controls. Binge alcohol use was clearly documented as the proximal maternal risk factor for FASD, and significant distal risk factors were: low body mass, education, and income; high gravidity, parity, and age at birth of the index child. FAS rates continue to extremely high in these communities at 89-129 per 1000 children. Total FASD affect 196-276 per 1000 or 20-28% of the children in these communities. Conclusions: Very high rates of FASD persist in these general populations where regular, heavy drinking, often in a binge fashion, co-occurs with low socioeconomic conditions.

In addition to fetal alcohol syndrome and fetal alcohol spectrum disorders, prenatal alcohol exposure is associated with many other adverse pregnancy and birth outcomes. Research suggests that alcohol use during pregnancy may increase the risk of miscarriage, stillbirth, preterm delivery, and sudden infant death syndrome. This research has some inherent difficulties, such as the collection of accurate information about alcohol consumption during pregnancy and controlling for comorbid exposures and conditions. Consequently, attributing poor birth outcomes to prenatal alcohol exposure is a complicated and ongoing task, requiring continued attention to validated methodology and to identifying specific biological mechanisms.

The main objective of this study is to construct a profile on the child with Fetal alcohol syndrome that can assist individuals working with these children. The focus of the study is the recognition of the emotional needs of the child with Fetal alcohol syndrome. Most studies done previously suggest that children with Fetal alcohol syndrome show behaviour similar to children with Attention Deficit Hyperactive Disorder. Although a child with Fetal alcohol syndrome shows the same characteristics as a child with Attention Deficit Hyperactive Disorder, the manifestation of their emotional needs differ. The Child with Attention Deficit Hyperactive Disorder does not necessarily show symptoms of cognitive developmental delay where the child with Fetal alcohol syndrome show symptoms of cognitive developmental delays. A Gestalt play therapy model has been used to show that through play therapy the child with Fetal alcohol syndrome can be guided to emotional awareness. These techniques are easy to use and applicable in class situations where the childcare worker, teachers or counselor work with the child with Fetal alcohol syndrome. The empirical research was done by means of quantitative research with was done by using the Conner symptom checklist to determine if the child with Fetal alcohol syndrome is hyperactive and impulsive and qualitative research with was done by means of participating observation Gestalt play therapy with the child with Fetal alcohol syndrome. The results show that the child with Fetal alcohol syndrome is hyperactive, impulsive and inattentional. These guidelines provided in the study will help the teacher and the child with Fetal alcohol syndrome cope better in the classroom environment and the child will learn how to cope with his emotional behaviours. / Social Work / M. Diac. (Play Therapy)