Ethanol exposure during pregnancy is one of the leading causes of preventable birth defects, leading to a range of symptoms collectively known as fetal alcohol spectrum disorder (FASD). More moderate levels of prenatal ethanol exposure (PNE) lead to a range of behavioural deficits including aggression, poor social interaction, poor cognitive performance and increased likelihood of addiction in later life. Current theories suggest that adaptation in the hypothalamic-pituitaryadrenal (HPA) axis and neuroendocrine systems contributes to mood alterations underlying behavioural deficits and vulnerability to addiction. This has led to the suggestion that corticotrophin-releasing factor (CRF) antagonists and glucocorticoid (steroid) inhibitors may be potential therapeutics to address the deficits of PNE and for the treatment of addiction. The zebrafish (Danio rerio) has several advantages over mammalian models, such as low cost of maintenance, short life cycle, easy embryological manipulation and the possibility of large-scale genetic screening. By using this model, our aim is to determine whether developmental ethanol exposure provokes changes in the HPA axis (HPI axis in fish), as it does in mammalian models, therefore opening the possibilities of using zebrafish to elucidate the mechanisms involved, and to test novel therapeutics to alleviate deleterious symptoms. Thus this thesis focuses solely on the effect of developmental ethanol exposure on the functioning of the HPI axis in zebrafish. Stress-reactivity in zebrafish larvae ethanol-treated 1-9 days post 4 fertilisation (dpf) was assessed using thigmotaxis and thigmotaxis following airstress. In both tests, lower stress-related responses were obtained with ethanol treated animals, in that they spent less time at the edges of the apparatus (P<0.01, n=3). They also showed lower total body cortisol (P=0.04, n=14). Larvae also showed the same behaviour pattern two weeks after ethanol exposure, (23dpf) (P=0.04, n=3), again with reduced total cortisol (P=0.03, n=4). HPI-related gene transcription was also assessed in 9dpf ethanol treated zebrafish larvae, by qRT-PCR. Revealing up-regulation of CRH, CRHBP and CRHR2, normalized against β-Actin, Elav1 and Gap43 housekeeping genes. In situ hybridization revealed no spatial changes in CRH, CRH-BP and POMC with animals at the same stage. Behavioural stress-reactivity differences in 6-months old adults that had been exposed developmentally to ethanol were assessed using novel tank diving and thigmotaxis. Both assays indicated a decrease in stress-like behaviour due to early ethanol exposure compared to controls (P<0.05, n=5 both). Finally, cortisol levels were assayed from 9dpf larvae and 6-month-old adults that had been treated with ethanol during early development showed a significant reduction in cortisol output when air-exposed stressed compared to controls (P=0.04, n=5). Conclusion: Early ethanol exposure produced significant changes in cortisol, HPI gene mRNA expression and stress-reactive behaviour in 9dpf animals. Changes in cortisol and behaviour were still detected in 6-months old adults, developmentally treated with ethanol, indicating that early ethanol exposure has permanent effects on the HPI axis. 5 As our data contradicts the findings in mammalian literature where early ethanol exposure increases stress-like behaviour in later life, it is also possible that more permanent effects of PNE in mammals may arise through maternal-offspring interactions, during and post gestation, such as breastfeeding and maternal grooming of the offspring, which are absent in the zebrafish model.

The cognitive and/or behavioural problems associated with Fetal Alcohol Spectrum Disorder (FASD) place this population at increased risk of involvement in the justice system. Although FASD poses challenges at each stage of the justice system, legal discussion and commentary have pinpointed the sentencing stage as the phase in which the issue of FASD is most commonly raised and considered. The purpose of this study is to examine if (and how) FASD is being taking into consideration at sentencing. To this end, a comparative analysis of 87 sentencing judgments (42 FASD offenders and 45 non-FASD offenders) reported in Quicklaw was conducted. Cases were matched on most serious offence (assault, robbery and sexual assault) and jurisdiction (Yukon, British Columbia and Ontario). Descriptions of FASD and non-FASD offenders as reported by judges were found to differ in a number of significant ways. Similarly, sentencing purposes applied to each offender group emerged as distinct. Despite these distinctions, no differences were found in the type and length of sentence handed down (even after controlling for criminal record and breaches). These findings indicate a need for further research and possible policy changes.

The cognitive and/or behavioural problems associated with Fetal Alcohol Spectrum Disorder (FASD) place this population at increased risk of involvement in the justice system. Although FASD poses challenges at each stage of the justice system, legal discussion and commentary have pinpointed the sentencing stage as the phase in which the issue of FASD is most commonly raised and considered. The purpose of this study is to examine if (and how) FASD is being taking into consideration at sentencing. To this end, a comparative analysis of 87 sentencing judgments (42 FASD offenders and 45 non-FASD offenders) reported in Quicklaw was conducted. Cases were matched on most serious offence (assault, robbery and sexual assault) and jurisdiction (Yukon, British Columbia and Ontario). Descriptions of FASD and non-FASD offenders as reported by judges were found to differ in a number of significant ways. Similarly, sentencing purposes applied to each offender group emerged as distinct. Despite these distinctions, no differences were found in the type and length of sentence handed down (even after controlling for criminal record and breaches). These findings indicate a need for further research and possible policy changes.

Alcohol consumption during pregnancy is one potential risk factor for spontaneous abortion (SAb). Prior research suggested that heavy drinking during pregnancy was associated with significantly increased rates of SAb, but results for lower levels of drinking have been inconsistent. We examined the association between different levels and patterns of prenatal alcohol consumption and SAb in a high-risk inner-city sample. We hypothesized that higher levels, binge patterns, and more frequent drinking would be associated with increased rates of SAb. The quantity and frequency of self-reported peri-conceptional and repeated in-pregnancy maternal drinking volumes per beverage type were assessed with semi-structured interviews in a prospective subsample of 302 African-American mothers. Relations between various measures of prenatal alcohol exposure and SAb were assessed using logistic regression. After controlling for various potential confounders, there was a significant positive relation between average absolute alcohol use per day across pregnancy and SAb. Greater frequency of drinking episodes also predicted SAb: an average of even one day of drinking per week across pregnancy was associated with an increase in the incidence of SAb. However, contrary to our hypothesis, neither the amount of alcohol drunk per drinking day nor a measure of binge drinking was significantly related to SAb after controlling for confounders. Differences in when women who drank at risk levels initiated antenatal care may have under-estimated the impact of alcohol on SAb in this low-SES urban African-American sample. Some drinking measures averaged across pregnancy may have under-estimated consumption and overestimated risk of SAb, but other risk drinking measures that avoid this limitation show similar relations to SAb. Identifying fetal risk drinking in pregnant women is critical to increasing the effectiveness of interventions that reduce risk level alcohol consumption and protect from pregnancy loss.

Background: Fetal alcohol spectrum disorders (FASD), which are caused by prenatal alcohol exposure (PAE), affects people around the world. Certain communities in South Africa have among the highest reported incidences of fetal alcohol syndrome (FAS) in the world. Although PAE-related brain alterations have been widely documented, the mechanisms whereby alcohol affects the brain are not clearly understood. MRI relaxation parameters T1, T2, T2* and proton density (PD), are basic tissue properties that reflect the underlying biology. The present study aims to advance our understanding of how PAE alters the microstructural properties of tissue by examining PAE-related changes in these tissue parameters in adolescents with FASD. Methods: The final sample used in this study consisted of 53 children from a previously studied longitudinal cohort (Jacobson et al., 2008) and 12 additionally recruited subjects. Of the 65 participants, 18 were diagnosed with FAS or partial FAS (PFAS) and made up the FAS/PFAS group, 18 were diagnosed as heavily exposed non-syndromal (HE) and 29 were age matched controls. Subjects were scanned at the Cape Universities Body Imaging Centre (CUBIC) located at Groote Schuur Hospital on a 3T Siemens Skyra MRI. Structural images were obtained using the MEMPRAGE sequence. From these images T1, T2, T2* and PD parameter maps were constructed and segmented into 43 regions of interest (ROI) using Freesurfer, FSL and AFNI. Linear regression analyses were used to analyse group differences as well as correlations between parameter values and the amount of alcohol the mother consumed during pregnancy. Results: Significant T1 differences were found in the caudate, cerebellar cortex, hippocampus, accumbens, putamen, choroid plexus, ventral diencephalon (DC), right vessel and ventricles. Significant T2 differences were found in the caudate, brain stem, corpus callosum (CC), amygdala, cerebral cortex, choroid plexus, vessels and ventricles. Significant T2* differences were found in the cerebellar cortex, optic chiasm and ventricles. Significant PD differences were found in the hippocampus and left lateral ventricle. The exploratory nature of this study resulted in none of the results surviving FDR correction for multiple comparisons. Conclusions: Overall, our findings point to regional PAE-related increases in water content and cellular and molecular changes in underlying tissue of the anatomical structure. Exceptions were the right cerebral cortex, brain stem, hippocampus, amygdala and ventral diencephalon where our findings point to less free water and increased cell density, and cerebellar cortex where simultaneous reductions in T1 and T2* suggest the possibility of increased iron content. In highly myelinated white matter structures, such as the CC and optic chiasm, our results point to PAErelated demyelination, and possibly increased iron. These findings extend previous knowledge of effects of PAE and demonstrate that tissues are affected at a microstructural level.

Thesis (MA)--Stellenbosch University, 2014. / ENGLISH ABSTRACT: Maternal drinking during pregnancy and its consequences are a growing health concern worldwide. It has also been identified as a significant problem in South African communities with some of the highest prevalence rates of Fetal Alcohol Spectrum Disorder (FASD) reported in South Africa. The primary aim of this study was to explore how women in a South African community in the Northern Cape Province perceive the personal and general risk of drinking during pregnancy. The secondary aims were to ascertain whether there was evidence of unrealistic optimism, to examine whether there were personal characteristics that are associated with high or low risk perception, and to examine women‟s knowledge of FASD. A total of 128 women from De Aar in the Northern Cape, an area with a high prevalence of FASD, and therefore drinking during pregnancy, were recruited to take part in the study. Participants had previously taken part in a FASD prevention programme. Questionnaires were administered assessing the perception of the risk posed to a participant‟s own child should she drink during pregnancy, and the risk posed to others‟ children should they drink during pregnancy. The questionnaire also contained questions on FASD knowledge and demographic variables. Participants were between 18 and 44 years of age and reported high rates of unemployment. Most women had more than one child and 7.8% had a child diagnosed with FASD. No evidence for unrealistic optimism was found. Multiple regression analyses revealed both FASD knowledge, and the perception of how easy it would be for oneself to stop drinking, were significant predictors for both personal and general risk. A model including the perception of general risk, FASD knowledge and the perception of how easily one could stop drinking accounted for the most variance in the perception of personal risk (66.4%). Perception of personal risk on its own was the strongest predictor of the perception of general risk accounting for 56.1% of variance. There was no significant correlation between passage of time and FASD knowledge, but possible gaps in FASD knowledge were identified. The study provides an overview of the perception of the risk of drinking during pregnancy in the target population. It also suggests improvements to the research design and materials for further research. / AFRIKAANSE OPSOMMING: Moederlike drankgebruik gedurende swangerskap en die gevolge daarvan word wêreldwyd met groeiende kommer beskou. Dit is ook as ʼn wesenlike probleem in Suid-Afrika geïdentifiseer, met van die hoogste voorkomssyfers van Fetale Alkohol Spektrumafwykings (FASA) wat in Suid-Afrika aangeteken is. Die primêre doel van hierdie studie was om, in ʼn Suid-Afrikaanse gemeenskap in die Noord Kaap provinsie, die persepsie van persoonlike en algemene risiko van drink tydens swangerskap onder vrouens, te ondersoek. Die sekondêre doelstellings was om vas te stel of daar bewyse van onrealistiese optimisme is; te bepaal of daar persoonlike eienskappe is wat korreleer met ʼn hoë of lae risiko-persepsie, en om ook die vroue se kennis van Fetale Alkohol Spektrumafwykings (FASA) te ondersoek. 128 vroue van De Aar in die Noord-Kaap is gewerf om aan die studie deel te neem. Die gebied het 'n hoë FASA voorkoms, en dus ook alkoholgebruik tydens swangerskap. Deelnemers het voorheen deelgeneem aan 'n FASA voorkomingsprogram. Vraelyste is voltooi rakende die persepsie van die risiko vir 'n deelnemer se eie kind sou sy tydens swangerskap drink, en die risiko vir ander se kinders, sou hulle tydens swangerskap drink. Die vraelys het ook vrae oor FASA kennis en demografiese veranderlikes ingesluit. Deelnemers was tussen 18 en 44 jaar oud en het hoë vlakke van werkloosheid gerapporteer. Meeste vrouens het meer as een kind gehad en 7.8% het ʼn kind wat met FASA gediagnoseer is gehad. Geen bewyse vir onrealistiese optimisme is gevind nie. Meervoudige regressie-ontleding het bevind dat beide FASA-kennis en die persepsie van hoe maklik dit vir ‟n deelnemer self sou wees om op te hou drink, beduidende voorspellers vir beide persoonlike en algemene risiko is. 'n Model wat die persepsie van algemene risiko, FASA-kennis en die persepsie van hoe maklik 'n deelnemer self kan ophou drink, het die grootste variansie in die persepsie van persoonlike risiko verduidelik (66,4 %). Persepsie van persoonlike risiko op sy eie, was die sterkste voorspeller van die persepsie van algemene risiko, opsigself verantwoordelik vir 56,1% van die variansie. Daar was geen beduidende korrelasie tussen die verloop van tyd en FASA kennis nie, maar moontlike gapings in die kennis van FASA is geïdentifiseer. Die studie bied 'n oorsig van die persepsie van die risiko van drankgebruik tydens swangerskap in die teikenbevolking. Dit stel ook verbeteringe vir die navorsingsmetodiek voor vir toekomstige navorsing.

The Ph.D. dissertation encompasses an interdisciplinary study exploring qualitative, holistic strategies for individuals with Fetal Alcohol Spectrum Disorder (FASD) in integrated areas of law, medicine, education, psychology and justice, through both inductive analysis of field research as well as through relevant documentary analysis, incorporating a global or comparative component. Compliance with Guidelines for Research Involving Aboriginal Peoples has been sustained through community partnerships with various First Nations and Métis Communities, Elders and Parents, as well as with an FASD Parental Advocacy Group, advised by a team of interdisciplinary researchers in the academy. Accordingly, emergent research protocols were co-constructed through ongoing collaboration with the various community partners. In Aboriginal research, it is essential not to parachute in and out of communities with the data, but rather to forge genuine, collaborative, long term partnerships, and to build capacity in those communities.<p> The dissertation format approved by the Student Advisory Committee is Manuscript Style, a format approved by the University of Saskatchewans College of Graduate Studies and Research (formerly referred to as X-Format) similar to a self-edited book or collection of articles with introduction, sub-text, intra-text and general discussion to link the manuscripts. The various manuscripts comprising the present thesis include:<p> 1.Framing the Research Anthology: A Vision Quest, Ékehohksimoht Ke-kiss-see Muya<p> Section One situates the research style, process, approach, substance and rationale of the dissertation. It is largely situated within holistic Indigenous epistemologies, which may require a paradigm shift, in contrast to more bounded western world views.<p> Interdisciplinary, holistic, community-based research on the topic of FASD, including a search for solutions, extends globally, across the lifespan, and across sectors.<p> II. Indigenous Disadvantage and Despair, An Evaluation of Recent Strategies and Alternatives: Healing and Transformation, Pluralism and Reconciliation, Ne wah kuma ka tik<p> Section Two explores historical and contextual factors leading to a high prevalence of FASD, as well as strategies to overcome disadvantage, including Reconciliation, Treaty Processes, and Research as Reconciliation. Local Narratives are privileged over Meta-narratives, to counter the power of global market forces usurping the sphere of family, community and culture.<p> III. Disjunctures and Discontinuities in the Law of Mental Intent: FASD as a Site of Resistance and Transformation, Esquiskuit<p> Section Three examines the disconnect between medical knowledge of FASD, on the one hand, and the Laws of Mental Intent, on the other, inspiring a search for a unified, integrated theory of mental disorder and criminal responsibility that takes into account modern neurocognitive conditions like FASD. Section Three further explores the present piecemeal and compartmentalized rules for fitness, responsibility, various levels of mental intent, and a resultant rationale, substance and process of law reform and systemic change.<p> IV. FASD and Holistic Literacies: A Talking or Sharing Circle, Wa-sa-cam-e-be-ke-skue<p> Section Fours inductive themes comprise model practice guidelines for the gestalt of Literacy and FASD, derived from inductive analysis of qualitative data collected in the field research. The data was collected using Sharing Circles with Aboriginal Elders, Parents, and Mentors of Individuals with FASD; Conversational Interviews with Parents and Children with FASD; as well as Interviews and Focus Groups with various Professionals who support individuals with FASD and their Families. Special protocols were followed in creating and participating in the Indigenous Research, Sharing Circles and Conversational Interviews. Meta-paradigmatic analysis situates Indigenous Research Methodologies among emerging, multi-disciplinary, inductive methodologies suitable for understanding the infinite complexity of natural phenomena, such as FASD.<p> V. Epilogue: An Honour Song, Kethou-ne-ka-mon<p> Circles of healing, transformation and reconciliation heal wounds, reconcile differences, and transform paradigms of justice, health, education and governance, through the incorporation of models of equitable, holistic relationships with one another and with Mother Earth. Multidisciplinary and cross-cultural perspectives, dialogues between local and global, and particular and universal, become matrices to support new paradigms embodying broader reflections of reality.

The Ph.D. dissertation encompasses an interdisciplinary study exploring qualitative, holistic strategies for individuals with Fetal Alcohol Spectrum Disorder (FASD) in integrated areas of law, medicine, education, psychology and justice, through both inductive analysis of field research as well as through relevant documentary analysis, incorporating a global or comparative component. Compliance with Guidelines for Research Involving Aboriginal Peoples has been sustained through community partnerships with various First Nations and Métis Communities, Elders and Parents, as well as with an FASD Parental Advocacy Group, advised by a team of interdisciplinary researchers in the academy. Accordingly, emergent research protocols were co-constructed through ongoing collaboration with the various community partners. In Aboriginal research, it is essential not to parachute in and out of communities with the data, but rather to forge genuine, collaborative, long term partnerships, and to build capacity in those communities.<p> The dissertation format approved by the Student Advisory Committee is Manuscript Style, a format approved by the University of Saskatchewans College of Graduate Studies and Research (formerly referred to as X-Format) similar to a self-edited book or collection of articles with introduction, sub-text, intra-text and general discussion to link the manuscripts. The various manuscripts comprising the present thesis include:<p> 1.Framing the Research Anthology: A Vision Quest, Ékehohksimoht Ke-kiss-see Muya<p> Section One situates the research style, process, approach, substance and rationale of the dissertation. It is largely situated within holistic Indigenous epistemologies, which may require a paradigm shift, in contrast to more bounded western world views.<p> Interdisciplinary, holistic, community-based research on the topic of FASD, including a search for solutions, extends globally, across the lifespan, and across sectors.<p> II. Indigenous Disadvantage and Despair, An Evaluation of Recent Strategies and Alternatives: Healing and Transformation, Pluralism and Reconciliation, Ne wah kuma ka tik<p> Section Two explores historical and contextual factors leading to a high prevalence of FASD, as well as strategies to overcome disadvantage, including Reconciliation, Treaty Processes, and Research as Reconciliation. Local Narratives are privileged over Meta-narratives, to counter the power of global market forces usurping the sphere of family, community and culture.<p> III. Disjunctures and Discontinuities in the Law of Mental Intent: FASD as a Site of Resistance and Transformation, Esquiskuit<p> Section Three examines the disconnect between medical knowledge of FASD, on the one hand, and the Laws of Mental Intent, on the other, inspiring a search for a unified, integrated theory of mental disorder and criminal responsibility that takes into account modern neurocognitive conditions like FASD. Section Three further explores the present piecemeal and compartmentalized rules for fitness, responsibility, various levels of mental intent, and a resultant rationale, substance and process of law reform and systemic change.<p> IV. FASD and Holistic Literacies: A Talking or Sharing Circle, Wa-sa-cam-e-be-ke-skue<p> Section Fours inductive themes comprise model practice guidelines for the gestalt of Literacy and FASD, derived from inductive analysis of qualitative data collected in the field research. The data was collected using Sharing Circles with Aboriginal Elders, Parents, and Mentors of Individuals with FASD; Conversational Interviews with Parents and Children with FASD; as well as Interviews and Focus Groups with various Professionals who support individuals with FASD and their Families. Special protocols were followed in creating and participating in the Indigenous Research, Sharing Circles and Conversational Interviews. Meta-paradigmatic analysis situates Indigenous Research Methodologies among emerging, multi-disciplinary, inductive methodologies suitable for understanding the infinite complexity of natural phenomena, such as FASD.<p> V. Epilogue: An Honour Song, Kethou-ne-ka-mon<p> Circles of healing, transformation and reconciliation heal wounds, reconcile differences, and transform paradigms of justice, health, education and governance, through the incorporation of models of equitable, holistic relationships with one another and with Mother Earth. Multidisciplinary and cross-cultural perspectives, dialogues between local and global, and particular and universal, become matrices to support new paradigms embodying broader reflections of reality.

This institutional ethnography relies on observations, interviews, and textual analyses to explore the experiences of mothers and children who attend a women-centered agency in Vancouver, Canada where a hot lunch, child care in the emergency daycare, and participation in group activities are vital forms of support. Mothers who come to the centre have many concerns related to their need for safe housing, a sustainable income, adequate food, child care, and support. And like mothers anywhere, they have concerns about their children. While many of the children, the majority of them First Nations, have never had a diagnostic assessment for fetal alcohol syndrome (FAS) or for the relatively new umbrella category, ‘fetal alcohol spectrum disorder’ (FASD), a number of the mothers were concerned or even knew that their children had FAS. This thesis asks – how does it happen that mothers have come to know their children in this way? The study critically examines how FASD knowledge and practices actually work in the setting and what they accomplish. My analysis traces how ruling practices for constructing and managing ‘problem’ mothers and children coordinate work activities for identifying children deemed to be ‘at risk’ for FASD. In their efforts to help their children and improve their opportunities for a better life, mothers become willing participants in group activities where they learn how to attach the relevancies of the FASD discourse to their children’s bodies or behaviours. They also gain instruction which helps them to confess their responsibility for children’s problems. While maternal alcohol use as the cause of FASD is contested in literature and in some work sites it is, in this setting, taken as a fact. This study discovers how institutional work processes involving government, medicine, and education actually shape and re-write women’s and children’s experiences into forms of knowledge that make mothers and children institutionally actionable. It is only by exposing the relations of power organizing mothers’ work that it may be possible to re-direct attention to mothers’ and children’s embodied concerns and relieve mothers of the overwhelming responsibility for which they are held and hold themselves to be accountable. / Graduate