O consumo de bebidas alcoólicas durante o período gestacional está relacionado a diversos prejuízos para a saúde materna e do bebê. O uso desta substância por gestantes pode aumentar o risco de trabalho de parto prematuro, aborto espontâneo, descolamento de placenta e aumento de pressão arterial. Em relação ao filho, o álcool pode causar deficiência no crescimento intrauterino, malformações físicas, a Síndrome Fetal do Álcool (SFA), danos cognitivos e problemas comportamentais que podem perdurar por toda a vida da criança. Embora exista uma tendência a diminuição do consumo de álcool durante o período gestacional, observa-se que uma parcela de mulheres persiste no consumo abusivo. Dessa forma, a identificação dos aspectos psicossociais relacionados com o uso de álcool torna-se importante para compreender melhor quais os fatores relacionados com este comportamento. O estudo teve como objetivo avaliar comparativamente os aspectos psicossociais associados com o uso de álcool em amostra de gestantes com diferentes padrões de consumo: abstinentes, consumidoras de risco, consumidoras nocivas e com provável dependência de álcool. Os fatores predisponentes para a SFA (conforme modelo adaptado de Abel & Hannigan) e o modelo psicossocial para compreensão do problema foram utilizados para seleção dos aspectos psicossociais considerados relevantes nesta pesquisa. Durante o desenvolvimento do estudo, a pesquisadora realizou estágio de doutorado no exterior na University of North Carolina at Chapel Hill (EUA) para treinamento clínico e científico. Trata-se de um estudo com delineamento transversal, observacional e comparativo. A coleta de dados foi realizada através de entrevistas semiestruturadas com gestantes atendidas em unidades básicas de saúde, maternidade e em serviço especializado em atendimento a mulheres farmacodependentes. Os resultados apontaram que gestantes com maior gravidade de consumo tiveram maior propensão à morbidade psiquiátrica (F=15,1; p<0,001), maior número de eventos estressores (F=21,9; p<0,001), menor suporte social (F=9,2; p<0,001), menor habilidade de coping (F=6,5; p<0,001), menor conhecimento sobre os danos associados ao uso de álcool na gestação (F=7,2; p<0,001) e tinham companheiro com uso de álcool (?²=5,8; p<0,01) e/ou drogas ilícitas (?²=24,3; p<0,001). A análise de regressão logística multivariada identificou quatro principais variáveis associadas à maior gravidade de uso de álcool: Estresse, Sintomas psiquiátricos, Uso de álcool e drogas do companheiro, Crenças e conhecimentos sobre o uso de álcool na gestação. Sendo assim, as gestantes com maior consumo de bebidas alcoólicas apresentaram aspectos psicossociais que as diferiram das gestantes abstinentes ou com consumo de risco de álcool. O estudo contribui ao evidenciar fatores que podem aumentar, ou ainda, moderar o consumo de álcool de gestantes. A gestação é um momento propício para auxiliar a mulher no abandono do uso de substâncias como bebidas alcoólicas. Os profissionais que atendem essa população podem avaliar tais aspectos psicossociais e detectar gestantes com maior vulnerabilidade para o uso de álcool. Portanto, o conhecimento sobre esta relação é importante para intervenções profissionais efetivas, formulação de estratégias de prevenção, diagnóstico precoce e tratamento, assim como uma melhor fundamentação de políticas públicas na área de saúde materno-infantil. / Alcohol consumption during pregnancy is related to several damage for maternal and newborn health. Pregnant women that use this substance can increases the risk for preterm labor, miscarriage, placental abruption and high blood pressure. For the child, alcohol can result in intrauterine growth restriction, physical malformations, the Fetal Alcohol Syndrome (FAS), cognitive impairment and behavioral problems that can last for a child\'s whole life. Although there is a tendency to decreased alcohol consumption during pregnancy, it is observed that a portion of women persists in the abuse. Thus, the identification of psychosocial aspects of alcohol use becomes important to better understand what factors are related to this behavior. The goal of the study was comparatively evaluate the psychosocial aspects associated with the alcohol use in a sample of pregnant women with different patterns of consumption: abstinence, hazardous use, harmful use and alcohol dependence. Permissive factors for FAS (as adapted model of Abel & Hannigan) and the psychosocial model for understanding the issue were used for selecting the psychosocial aspects considered relevant for this search. During the development of the study, the researcher conducted internship abroad at the University of North Carolina at Chapel Hill (USA) for clinical and scientific training. A cross-sectional, observational and comparative study. Data collection was conducted through semi-structured interviews with pregnant women attending the Basic Health Units, a maternity clinic and specialized service in addiction treatment for women. Results indicated that pregnant women with greater severity consumption were more chance to psychiatric morbidity (F=15.1, p<0.001), stressful events numbers (F=21.9, p<0.001), lower social support (F=9.2; p<0.001), lower levels of coping (F=6.5; p<0.001), lower Beliefs and Knowledge about the harms associated with alcohol use during pregnancy (F=7.2; p <0.001) and had a partner with alcohol use (X²=5.8; p<0.01) and/or illicit drug use (X²=24.3, p<0.001). Multivariate logistic regression analysis identified four main variables associated with greater severity of alcohol use: Stress, Psychiatric symptoms, Partner who use alcohol or drugs, Beliefs and Knowledge about alcohol use during pregnancy. Thus, pregnant women with greater severity of alcohol consumption had psychosocial aspects that differ from abstinent women or with hazardous alcohol consumption. This research identified factors that may increase or, even moderate alcohol consumption for pregnant women. Pregnancy seems to be appropriate moment to aid the woman in the abandonment of the use of substances such as alcohol. Professionals serving this population could evaluate this psychosocial aspects and detecting pregnant women with greater vulnerability to alcohol use. Therefore, knowledge of this association is important for effective professionals interventions, formulation of strategies for prevention, early diagnosis and treatment, as well as a better foundation for public policy about maternal and child health.

O consumo de bebidas alcoólicas durante o período gestacional está relacionado a diversos prejuízos para a saúde materna e do bebê. O uso desta substância por gestantes pode aumentar o risco de trabalho de parto prematuro, aborto espontâneo, descolamento de placenta e aumento de pressão arterial. Em relação ao filho, o álcool pode causar deficiência no crescimento intrauterino, malformações físicas, a Síndrome Fetal do Álcool (SFA), danos cognitivos e problemas comportamentais que podem perdurar por toda a vida da criança. Embora exista uma tendência a diminuição do consumo de álcool durante o período gestacional, observa-se que uma parcela de mulheres persiste no consumo abusivo. Dessa forma, a identificação dos aspectos psicossociais relacionados com o uso de álcool torna-se importante para compreender melhor quais os fatores relacionados com este comportamento. O estudo teve como objetivo avaliar comparativamente os aspectos psicossociais associados com o uso de álcool em amostra de gestantes com diferentes padrões de consumo: abstinentes, consumidoras de risco, consumidoras nocivas e com provável dependência de álcool. Os fatores predisponentes para a SFA (conforme modelo adaptado de Abel & Hannigan) e o modelo psicossocial para compreensão do problema foram utilizados para seleção dos aspectos psicossociais considerados relevantes nesta pesquisa. Durante o desenvolvimento do estudo, a pesquisadora realizou estágio de doutorado no exterior na University of North Carolina at Chapel Hill (EUA) para treinamento clínico e científico. Trata-se de um estudo com delineamento transversal, observacional e comparativo. A coleta de dados foi realizada através de entrevistas semiestruturadas com gestantes atendidas em unidades básicas de saúde, maternidade e em serviço especializado em atendimento a mulheres farmacodependentes. Os resultados apontaram que gestantes com maior gravidade de consumo tiveram maior propensão à morbidade psiquiátrica (F=15,1; p<0,001), maior número de eventos estressores (F=21,9; p<0,001), menor suporte social (F=9,2; p<0,001), menor habilidade de coping (F=6,5; p<0,001), menor conhecimento sobre os danos associados ao uso de álcool na gestação (F=7,2; p<0,001) e tinham companheiro com uso de álcool (?²=5,8; p<0,01) e/ou drogas ilícitas (?²=24,3; p<0,001). A análise de regressão logística multivariada identificou quatro principais variáveis associadas à maior gravidade de uso de álcool: Estresse, Sintomas psiquiátricos, Uso de álcool e drogas do companheiro, Crenças e conhecimentos sobre o uso de álcool na gestação. Sendo assim, as gestantes com maior consumo de bebidas alcoólicas apresentaram aspectos psicossociais que as diferiram das gestantes abstinentes ou com consumo de risco de álcool. O estudo contribui ao evidenciar fatores que podem aumentar, ou ainda, moderar o consumo de álcool de gestantes. A gestação é um momento propício para auxiliar a mulher no abandono do uso de substâncias como bebidas alcoólicas. Os profissionais que atendem essa população podem avaliar tais aspectos psicossociais e detectar gestantes com maior vulnerabilidade para o uso de álcool. Portanto, o conhecimento sobre esta relação é importante para intervenções profissionais efetivas, formulação de estratégias de prevenção, diagnóstico precoce e tratamento, assim como uma melhor fundamentação de políticas públicas na área de saúde materno-infantil. / Alcohol consumption during pregnancy is related to several damage for maternal and newborn health. Pregnant women that use this substance can increases the risk for preterm labor, miscarriage, placental abruption and high blood pressure. For the child, alcohol can result in intrauterine growth restriction, physical malformations, the Fetal Alcohol Syndrome (FAS), cognitive impairment and behavioral problems that can last for a child\'s whole life. Although there is a tendency to decreased alcohol consumption during pregnancy, it is observed that a portion of women persists in the abuse. Thus, the identification of psychosocial aspects of alcohol use becomes important to better understand what factors are related to this behavior. The goal of the study was comparatively evaluate the psychosocial aspects associated with the alcohol use in a sample of pregnant women with different patterns of consumption: abstinence, hazardous use, harmful use and alcohol dependence. Permissive factors for FAS (as adapted model of Abel & Hannigan) and the psychosocial model for understanding the issue were used for selecting the psychosocial aspects considered relevant for this search. During the development of the study, the researcher conducted internship abroad at the University of North Carolina at Chapel Hill (USA) for clinical and scientific training. A cross-sectional, observational and comparative study. Data collection was conducted through semi-structured interviews with pregnant women attending the Basic Health Units, a maternity clinic and specialized service in addiction treatment for women. Results indicated that pregnant women with greater severity consumption were more chance to psychiatric morbidity (F=15.1, p<0.001), stressful events numbers (F=21.9, p<0.001), lower social support (F=9.2; p<0.001), lower levels of coping (F=6.5; p<0.001), lower Beliefs and Knowledge about the harms associated with alcohol use during pregnancy (F=7.2; p <0.001) and had a partner with alcohol use (X²=5.8; p<0.01) and/or illicit drug use (X²=24.3, p<0.001). Multivariate logistic regression analysis identified four main variables associated with greater severity of alcohol use: Stress, Psychiatric symptoms, Partner who use alcohol or drugs, Beliefs and Knowledge about alcohol use during pregnancy. Thus, pregnant women with greater severity of alcohol consumption had psychosocial aspects that differ from abstinent women or with hazardous alcohol consumption. This research identified factors that may increase or, even moderate alcohol consumption for pregnant women. Pregnancy seems to be appropriate moment to aid the woman in the abandonment of the use of substances such as alcohol. Professionals serving this population could evaluate this psychosocial aspects and detecting pregnant women with greater vulnerability to alcohol use. Therefore, knowledge of this association is important for effective professionals interventions, formulation of strategies for prevention, early diagnosis and treatment, as well as a better foundation for public policy about maternal and child health.

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.