Introdução: O monitoramento do ganho de peso gestacional é de extrema importância nos cuidados pré-natais, pois pode evitar diversos desfechos desfavoráveis tanto para mãe quanto para o bebê. A maioria dos países utiliza algum tipo de referência para o acompanhamento do peso gestacional. Essas referências, muitas vezes, são baseadas em suas próprias populações ou em populações de outros países. Considerando-se que características populacionais variam de acordo com etnia, localização geográfica, hábitos alimentares, medidas antropométricas e condições socioeconômicas, dentre outros fatores, as recomendações baseadas em populações específicas são preferíveis para monitorar o peso gestacional. Várias metodologias são utilizadas para a construção de referências de peso gestacional. A OMS (Organização Mundial da Saúde) recomenda utilizar estudos longitudinais, a partir de populações selecionadas com baixa prevalência de complicações maternas e fetais. No Brasil, as referências utilizadas para peso gestacional são baseadas em duas populações internacionais; essas populações não utilizaram estudos longitudinais para gerar as referências, o que faz com que o Brasil necessite desenvolver sua própria abordagem para o monitoramento do peso gestacional. Objetivo: Construir uma curva de peso gestacional a partir de uma coorte de gestantes brasileiras, utilizando a metodologia estatística recomendada pela OMS para a construção das curvas padrão de crescimento infantil. Método: Dados do Estudo Brasileiro de Diabetes Gestacional (EBDG), estudo multicêntrico que reuniu gestantes de seis capitais brasileiras (Porto Alegre, Rio de Janeiro, São Paulo, Salvador, Manaus e Fortaleza), foram utilizados para a construção da curva. Foram selecionadas 2.103 gestantes eutróficas, de acordo com IOM (Institute of Medicine) (2009), com bons desfechos gestacionais, ou seja, foram excluídas gestantes com diabetes mellitus gestacional, com distúrbios hipertensivos, com gestações múltiplas e com partos prematuros (<37 semanas de gestação); excluíram-se também casos de gestantes com recém-nascidos de baixo peso ao nascer (BPN) ou com recém-nascidos grandes para a idade gestacional (GIG) e recém-nascidos pequenos para a idade gestacional (PIG), bem como casos de macrossomia. Dentre essas gestantes eutróficas, foram sorteadas 918, que irão fazer parte da validação da curva. Para a construção da curva, ficaram 1.179 gestantes eutróficas com bons desfechos gestacionais. Para o ajuste, foi utilizado o método GAMLSS (Modelos Aditivos Generalizados de Localização, Escala e Forma) do software R, que estimou os percentis 3, 5, 10, 25, 75, 90, 95 e 97. Após algumas exclusões, a segunda etapa do trabalho utilizou as 918 sorteadas (gestantes eutróficas com bons desfechos) e mais 901 gestantes eutróficas que tinham pelo menos um dos desfechos gestacionais indesejáveis descritos acima (com exceção de gestações múltiplas e diabetes mellitus), totalizando 1.817 gestantes para o grupo de validação. Com os percentis estimados pela curva de peso gestacional, foram definidos pontos de corte que determinaram os fatores de risco para os desfechos de interesse. A influência dos fatores de risco sobre os desfechos foi medida através do risco relativo (RR) e seus respectivos intervalos, com 95% de confiança, estimados através de regressão de Poisson com variância robusta. Os riscos relativos e seus respectivos intervalos de 95% de confiança foram estimados para a exposição em algum momento da gestação e para a exposição em algum momento dentro de cada trimestre. Os percentis foram avaliados sem ajustar para nenhum possível fator de confusão. Resultados: Após testados vários modelos GAMLSS, o que melhor ajustou os dados foi o que utilizou a família de distribuição BCPE (Box Cox de Potência Exponencial), com suavizador pb (B-splines), utilizando dois parâmetros e . O percentil 25 estimado foi capaz de predizer baixo peso ao nascer, prematuridade e PIG; já o percentil 75 pôde ser utilizado como preditor de distúrbios hipertensivos, macrossomia e GIG. Conclusão: o modelo obtido para a construção da curva de peso gestacional indicou que a relação entre peso gestacional e idade gestacional não é linear. A flexibilidade da metodologia estatística utilizada no estudo é suficiente para que possa ser aplicada utilizando-se o Índice de Massa corporal (IMC) em vez de peso gestacional. Essa metodologia também apresenta uma série de vantagens no que diz respeito às suas opções de modelagem. As curvas de percentis ajustadas foram eficientes em predizer desfechos gestacionais adversos. A metodologia aplicada nesta tese pode ser replicada para todas as categorias de IMC pré-gestacional. / Introduction: Monitoring gestational weight gain is extremely important in prenatal care, as it can avoid a series of unfavorable outcomes both for the mother and for the baby. Most countries use some kind of reference to follow up gestational weight. These references are often based in their own populations or in populations from other countries. Considering that population characteristics vary according to ethnics, geographical location, eating habits, anthropometric measures and socio-economic conditions, among other factors, recommendations based on specific populations are preferable to measure gestational weight. Several methodologies are used in the construction of references of gestational weight. WHO (World Health Organization) recommends using longitudinal studies based on selected populations with low prevalence of maternal and fetal complications. In Brazil the references used for gestational weight are based in two international populations which did not use longitudinal studies to generate the references, which brings to Brazil the need to develop its own approach to monitor gestational weight. Purpose: Build a gestational weight curve based on a Brazilian pregnant women cohort using the statistical methodology recommended by WHO to build standard curves of child growth. Method: Data from the Brazilian Gestational Diabetes Study, multicentric study which gathered women from six Brazilian capital cities (Porto Alegre, Rio de Janeiro, São Paulo, Salvador, Manaus and Fortaleza), was used to build the curve. 2,103 eutrophic pregnant women were selected, according to the IOM (Institute of Medicine) (2009), with good gestational outcomes, that is, there was an exclusion of pregnant women with: gestational diabetes mellitus, hypertensive disorders, multiple pregnancies, preterm deliveries (less than 37 weeks), newborns with low birth weight (LBW), large for gestational age newborns (LGA), small for gestational age newborns (SGA), and macrosomia. From these eutrophic pregnant women, 918 were drawn, who will be part of the validation curve. To build the curve 1,179 eutrophic pregnant women with good gestational outcomes remained. The method GAMLSS (Generalized Additive Models of Location, Scale and Shape) from the software R was used for adjustment, which estimated the percentiles 3, 5, 10, 25, 75, 90, 95 and 97. After some exclusions, the second stage of the work used the 918 drawn eutrophic pregnant women with good outcomes and other 901 eutrophic pregnant women who had at least one unwanted gestational outcomes described above (except for multiple pregnancies and diabetes mellitus), in a total of 1.817 pregnant women for the validation group. With the percentiles estimated by the gestational weight curve, cutoff points were defined which determined the risk factors for the interest outcomes. The influence of risk factors on the outcomes was measured through the relative risk (RR) and its respective intervals with 95% confidence, estimated by Poisson regression with strong variance. The relative risks and their respective intervals of 95% confidence for exhibition at some point during pregnancy and for exhibition at some moment in each trimester. The percentiles were assessed with no adjustment for any possible confounding factor. Results: After testing several GAMLSS methods, the one which best adjusted the data was the one which used the distribution family BCPE (Box Cox of Exponential Power), with pb smoothing (B-splines), using two parameters and . The percentil 25 estimated was able to predict low birth weight, prematurity and SGA, whereas the percentil 75 can be used as a predictor of hypertensive disorders, macrosomia and LGA. Conclusion: the model obtained for the gestational weight curve construction indicated that the relationship between gestational weight and gestational age is not linear. The flexibility of the statistical methodology used in the study is sufficient to be applied using BMI instead of gestational weight. This methodology also presents a series of advantages concerning its modeling options. The adjusted percentile curves were efficient to predict adverse gestational outcomes. The methodology applied in this thesis can be replicated for all pre gestational BMI categories.

No description available.

Introduction: Adequate calcium and vitamin D are needed for maternal and fetal health. Many pregnant women are not consuming enough calcium and are at high risk for vitamin D deficiency. Objectives: To 1) investigate the nutrition-related knowledge, opinions, and clinical practices of family physicians (FPs) towards prenatal calcium and vitamin D; and 2) determine the prevalence of meeting a predefined cut-off serum 25-hydroxyvitamin D concentration ([25-OHD]) for vitamin D sufficiency (≥ 75 nmol/L) in a cohort of pregnant women with gestational diabetes mellitus (GDM). Methods: Part 1: 500 surveys were mailed out to randomly selected FPs across Manitoba. Part 2: data were collected via retrospective chart review of 35 pregnant women with GDM attending a teaching hospital in Winnipeg, Manitoba between January 1, 2010 and December 31, 2013 and having one serum [25-OHD] measurement during their pregnancy. Results: Approximately one-third of FPs are discussing calcium and vitamin D requirements and supplements with their prenatal patients. The top three perceived barriers to delivery of calcium and vitamin D advice were more urgent issues, lack of time, and forgetting to do so. The mean serum [25-OHD] was 52.5 ± 24.1 nmol/L (range 14-109 nmol/L). Over half of women (51.4%) were vitamin D deficient ([25-OHD] < 50 nmol/L), and 28.6% of women were insufficient ([25-OHD] 50-74 nmol/L). Conclusions: Physicians would benefit from more training in nutrition. Multiple barriers exist that prevent FPs from providing calcium and vitamin D advice. Women with GDM have a high prevalence of vitamin D deficiency in our study. / February 2016

The overall aim of the thesis was to explore the perspectives of Chinese women with gestational diabetes mellitus (GDM) focused on their beliefs about health and illness and self-care behavior, the quality of care in China, and their lived experience.                       All the studies were conducted with qualitative methodology using individual interviews. Data were collected in obstetric clinics or wards at three different hospitals or the participants’ workplaces in the south east of China. Content analysis, according to Mayring, was used for data analysis in Study І (15 interviews) and Study II (17 interviews). Content analysis, according to Graneheim &amp; Lundman, was used for data analysis in Study III (44 interviews). In Study IV (18 interviews), data were analyzed by using phenomenological hermeneutics, according to Lindseth &amp; Norberg.      Three styles of beliefs about GDM among the Chinese women were explored in the thesis: GDM should be considered seriously; GDM was not a severe illness; and GDM was nothing to worry about. Correspondingly, three self-care behavior models were revealed: women strove to control GDM, and maintained their blood glucose values at a normal level; or women tried to control GDM based on the knowledge they received, but some of them felt helpless because the blood glucose level could not be maintained within the normal range; or women almost ignored GDM. They mainly sought help from professional sector and popular sector, and regarded health professionals and husbands as important people. They showed, however, that they sought a balance between following professionals’ advice and avoiding practical difficulties, which demonstrated the influence of health professionals, people around, and Chinese culture. The thesis highlighted a lack of knowledge, a lower level of risk awareness and poor self-care behavior among the women with GDM, as well as a lack of professional care resources for GDM and the lack of high-quality personalized care for the women. The core problem could be an resource imbalance between over-stretched hospitals and low-efficiency under-utilized primary healthcare centers. Their lived experience showed an eagerness to be cared for.     The thesis highlighted women’s call for caring care in China. The care of GDM for these women can most likely be improved by reform of clinical practice, particularly in primary healthcare services. It is necessary to increase the number of health professionals and material resources to a reasonable level, and to strengthen caring care in China.

Gestational diabetes mellitus (GDM) is a common complication of pregnancy and population health studies have linked it to impaired cognitive performance in the offspring. GDM triggers inflammatory responses, which can critically affect development of neuronal circuitry. We hypothesized that GDM promotes inflammatory responses in the fetus that can disturb fine-tuning of neuronal networks during early development, resulting in lifelong impaired cognitive functions. The cognitive performance of 15 week old offspring exposed to diet induced GDM were assessed. The brain tissue of the 15 week old and neonatal (E20) offspring were analyzed by immunohistochemistry, western blot, and cytokine assay. Cultured microglial responses to elevated glucose and/or fatty acid levels mimicking GDM associated diabetic conditions were analyzed. Our data reveals chronic neuroinflammation in GDM offspring, which combined with deregulation of microglial functions may explain hippocampal CA1 layer neuronal derangement and synaptic degradation that correlates with impaired cognitive performance of GDM offspring. / October 2016

Objetivo: O presente estudo teve por objetivo comparar duas estratégias de acompanhamento nutricional em pacientes com Diabetes Mellitus Gestacional em relação à composição da dieta dessas pacientes. Método: Durante o período de Julho de 2012 a Fevereiro de 2014, foram acompanhadas 55 gestantes no setor de Endocrinopatias e Gestação da Clínica Obstétrica do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP). Os critérios de inclusão foram: diagnóstico de DMG e idade gestacional inferior a 35 semanas na primeira avaliação nutricional. Foram excluídas as gestantes que não compareceram às consultas pré-estabelecidas (Grupo 1: duas avaliações; Grupo 2: quatro avaliações). As pacientes foram randomizadas em dois grupos: Grupo 1 (avaliação inicial e avaliação final) e Grupo 2 (avaliação inicial, orientação individualizada em mais dois encontros com intervalo de sete a quinze dias e avaliação final). Para avaliação do consumo inicial e final de nutrientes, bem como para nortear as orientação individualizadas (Grupo 2) utilizou-se o recordatório alimentar de 24h, seguido de análise no programa Nutrilife 8.0 ®. Na avaliação inicial, os dois grupos receberam orientação nutricional padrão. Para comparação entre os grupos, utilizou-se teste de qui-quadrado, exato de Fisher e teste de Mann-Whitney U. Resultados: Os dois grupos foram semelhantes em relação à ingestão de Macro e Micronutrientes na avaliação inicial. Na avaliação final, houve diferença estatisticamente significativa entre os grupos no que se refere ao consumo de carboidratos, lipídios e sódio. No Grupo 2, o consumo de carboidratos foi maior, e o de sódio e lipídios foi menor em comparação ao Grupo 1. Conclusões: A orientação individualizada, mesmo que avaliada em curto período de tempo, foi capaz de promover modificações no comportamento alimentar das gestantes em relação ao consumo de carboidratos, lipídios e sódio / Objective: The current study aimed the comparison of two strategies of nutrition monitoring of patients with Gestational Diabetes Mellitus compared to the diet composition of these patients. Method: From July 2012 to February, 2014, 55 pregnant women were monitored at the Endocrinopathy and Pregnancy Sector of the Obstetrics Clinic at Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP). The inclusion criterion was: GDM diagnosed and gestational age under 35 weeks at the first nutrition assessment. Pregnant women who attend the pre-established appointments (Group 1: two assessments; Group 2: four assessments) were removed. The patients were randomized into two groups: Group 1 (initial review and final review) and Group 2 (initial review, individual guidance in two appointments with a seven to fifteen day interval and final review). In order to assess the ideal initial and final consumption of nutrients, as well as to direct the individual guidance (Group 2), the 24h alimentary record was used, followed by the assessment on the Nutrilife 8.0® program. At the initial review, both groups received the standard nutritional guidance. In order to compare the two groups, a Chi-Square analysis, Fishers exact test and a Mann-Whitney U. test were performed. Results: the two groups were similar regarding the Macro and Micronutrients at the initial review. At the final review, there was a statistically significant difference between the groups with regards to the consumption of carbohydrates, lipids and sodium. In Group 2, there was a higher consumption of carbohydrates and the consumption of sodium and lipids was lower than in Group 1. Conclusions: The individual guidance, even if assessed in a short period of time, was capable of promoting changes in the alimentation behavior of the pregnant women with regards to the consumption of carbohydrates, lipids and sodium

Os estudos de metabolômica ganham importância a cada dia, por ajudarem a explicar processos biológicos em situações normais (fisiológicas) ou patológicas. Oferecem uma nova visão sobre o impacto funcional da expressão gênica, complementando os estudos de sequenciamento gênico, que negligenciam o impacto da exposição ao meio ambiente na etiologia de doenças. A metabolômica tem sido aplicada na toxicologia, mostrando que o perfil metabólico comparativo de duas situações, controle e teste, pode desempenhar um papel importante na descoberta e validação de biomarcadores, além de contribuir para o entendimento e consequente interpretação dos mecanismos de ação tóxica de xenobióticos. Este projeto de pesquisa tem por objetivo utilizar uma abordagem metabolômica para avaliar o impacto de alterações metabólicas no cérebro da prole de camundongos, ocorridas após exposição (via inalação) à fumaça decorrente da queima de maconha (Cannabis sativa). Fêmeas gestantes foram expostas a doses diárias de Cannabis sativa ou ar filtrado durante todo o período gestacional. Após o nascimento, os filhotes machos ao atingirem a idade para o desmame, considerado como fase adolescente, foram separados de suas respectivas mães e expostos à Cannabis sativa ou ar filtrado por mais 60 dias. As amostras de cérebro da prole foram submetidas a análises por cromatografia em fase gasosa acoplada a espectrometria de massas (CG-MS) numa abordagem metabolômica global (untargeted metabolomics). Os perfis metabólicos dos cérebros dos animais expostos (grupo teste) foram comparados com os obtidos na análise do grupo controle (não expostos), sendo identificados os metabólitos discriminadores candidatos. Estavam alterados os metabólitos: isoleucina, uréia, leucina, GABA, ácido succínico, ácido fumárico, serina, treonina, creatinina, ácido glutâmico, ácido acetilaspártico, glicerol -1 -fosfato, ácido ascórbico, tirosina, ácido cítrico, adenina, hipoxantina, inosina e uracila. A partir dos resultados apresentados, pode-se observar, que tanto a exposição gestacional à Cannabis sativa, quanto a exposição da prole na fase adolescente, provocam alterações metabólicas importantes. Os metabólitos significativamente alterados estão envolvidos no ciclo do ácido tricarboxílico, responsável pela respiração mitocondrial, na produção de energia, atuam na biossíntese de aminoácidos, glicólise, estresse oxidativo, podendo alterar o desenvolvimento e maturação do cérebro. Os resultados são preliminares, mas contribuem para o melhor entendimento dos mecanismos toxicológicos envolvidos na exposição crônica causada por essa droga, contribuindo para a prevenção e diagnóstico de danos no desenvolvimento fetal e adolescente. / Metabolomics studies gain importance each day because they help explain biological processes in normal (physiological) or pathological situations. They provide a new insight into the functional impact of environmental gene expression, complementing gene sequencing studies that neglect the impact of environmental exposure on the etiology of diseases. Metabolomics has been applied in toxicology, showing that the comparative metabolic profile of two situations, control and test, can play an important role in the discovery and validation of biomarkers, in addition to contributing to the understanding and interpretation of the toxic action mechanisms of xenobiotics. This research project aims to use a metabolomic approach to evaluate the impact of metabolic changes in the brain of the offspring of mice, which occurred after exposure (via inhalation) to the smoke from the burning Cannabis sativa. Pregnant females were exposed to daily doses of Cannabis sativa or filtered air throughout the gestational period. After birth, male offspring were reached adolescents weaning age were separated from their respective mothers and exposed to Cannabis sativa or to the filtrate for another 60 days. Offspring brain samples were analyzed by gas chromatography coupled to mass spectrometry (GC-MS) in a global metabolomic approach (non-target metabolomics). Metabolic profiles of the exposed animals brains (test group) were compared with those obtained in the control group (non-exposed), and the candidate discriminant metabolites were identified. The metabolites were altered: isoleucine, urea, leucine, GABA, succinic acid, fumaric acid, serine, threonine, creatine, glutamic acid, acetyl aspartic acid, glycerol-1-phosphate, ascorbic acid, tyrosine, citric acid, adenine, hypoxanthine, inosine and uracil were altered. From the results presented, it can be observed that both the gestational exposure in Cannabis sativa and the exposure of the adolescent phase exposure, induced important metabolic alterations. Significantly altered metabolites are involved in the tricarboxylic acid, which are responsible for mitochondrial respiration, in energy production, act at the amino acid biosynthesis, glycolysis, oxidative stress, which may alter the development and maturation of the brain. The results are preliminary but contribute to a better understanding of the mechanisms of toxicity and of fetal and adolescent infection.

Objetivo: O presente estudo teve por objetivo comparar duas estratégias de acompanhamento nutricional em pacientes com Diabetes Mellitus Gestacional em relação à composição da dieta dessas pacientes. Método: Durante o período de Julho de 2012 a Fevereiro de 2014, foram acompanhadas 55 gestantes no setor de Endocrinopatias e Gestação da Clínica Obstétrica do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP). Os critérios de inclusão foram: diagnóstico de DMG e idade gestacional inferior a 35 semanas na primeira avaliação nutricional. Foram excluídas as gestantes que não compareceram às consultas pré-estabelecidas (Grupo 1: duas avaliações; Grupo 2: quatro avaliações). As pacientes foram randomizadas em dois grupos: Grupo 1 (avaliação inicial e avaliação final) e Grupo 2 (avaliação inicial, orientação individualizada em mais dois encontros com intervalo de sete a quinze dias e avaliação final). Para avaliação do consumo inicial e final de nutrientes, bem como para nortear as orientação individualizadas (Grupo 2) utilizou-se o recordatório alimentar de 24h, seguido de análise no programa Nutrilife 8.0 ®. Na avaliação inicial, os dois grupos receberam orientação nutricional padrão. Para comparação entre os grupos, utilizou-se teste de qui-quadrado, exato de Fisher e teste de Mann-Whitney U. Resultados: Os dois grupos foram semelhantes em relação à ingestão de Macro e Micronutrientes na avaliação inicial. Na avaliação final, houve diferença estatisticamente significativa entre os grupos no que se refere ao consumo de carboidratos, lipídios e sódio. No Grupo 2, o consumo de carboidratos foi maior, e o de sódio e lipídios foi menor em comparação ao Grupo 1. Conclusões: A orientação individualizada, mesmo que avaliada em curto período de tempo, foi capaz de promover modificações no comportamento alimentar das gestantes em relação ao consumo de carboidratos, lipídios e sódio / Objective: The current study aimed the comparison of two strategies of nutrition monitoring of patients with Gestational Diabetes Mellitus compared to the diet composition of these patients. Method: From July 2012 to February, 2014, 55 pregnant women were monitored at the Endocrinopathy and Pregnancy Sector of the Obstetrics Clinic at Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP). The inclusion criterion was: GDM diagnosed and gestational age under 35 weeks at the first nutrition assessment. Pregnant women who attend the pre-established appointments (Group 1: two assessments; Group 2: four assessments) were removed. The patients were randomized into two groups: Group 1 (initial review and final review) and Group 2 (initial review, individual guidance in two appointments with a seven to fifteen day interval and final review). In order to assess the ideal initial and final consumption of nutrients, as well as to direct the individual guidance (Group 2), the 24h alimentary record was used, followed by the assessment on the Nutrilife 8.0® program. At the initial review, both groups received the standard nutritional guidance. In order to compare the two groups, a Chi-Square analysis, Fishers exact test and a Mann-Whitney U. test were performed. Results: the two groups were similar regarding the Macro and Micronutrients at the initial review. At the final review, there was a statistically significant difference between the groups with regards to the consumption of carbohydrates, lipids and sodium. In Group 2, there was a higher consumption of carbohydrates and the consumption of sodium and lipids was lower than in Group 1. Conclusions: The individual guidance, even if assessed in a short period of time, was capable of promoting changes in the alimentation behavior of the pregnant women with regards to the consumption of carbohydrates, lipids and sodium

Os estudos de metabolômica ganham importância a cada dia, por ajudarem a explicar processos biológicos em situações normais (fisiológicas) ou patológicas. Oferecem uma nova visão sobre o impacto funcional da expressão gênica, complementando os estudos de sequenciamento gênico, que negligenciam o impacto da exposição ao meio ambiente na etiologia de doenças. A metabolômica tem sido aplicada na toxicologia, mostrando que o perfil metabólico comparativo de duas situações, controle e teste, pode desempenhar um papel importante na descoberta e validação de biomarcadores, além de contribuir para o entendimento e consequente interpretação dos mecanismos de ação tóxica de xenobióticos. Este projeto de pesquisa tem por objetivo utilizar uma abordagem metabolômica para avaliar o impacto de alterações metabólicas no cérebro da prole de camundongos, ocorridas após exposição (via inalação) à fumaça decorrente da queima de maconha (Cannabis sativa). Fêmeas gestantes foram expostas a doses diárias de Cannabis sativa ou ar filtrado durante todo o período gestacional. Após o nascimento, os filhotes machos ao atingirem a idade para o desmame, considerado como fase adolescente, foram separados de suas respectivas mães e expostos à Cannabis sativa ou ar filtrado por mais 60 dias. As amostras de cérebro da prole foram submetidas a análises por cromatografia em fase gasosa acoplada a espectrometria de massas (CG-MS) numa abordagem metabolômica global (untargeted metabolomics). Os perfis metabólicos dos cérebros dos animais expostos (grupo teste) foram comparados com os obtidos na análise do grupo controle (não expostos), sendo identificados os metabólitos discriminadores candidatos. Estavam alterados os metabólitos: isoleucina, uréia, leucina, GABA, ácido succínico, ácido fumárico, serina, treonina, creatinina, ácido glutâmico, ácido acetilaspártico, glicerol -1 -fosfato, ácido ascórbico, tirosina, ácido cítrico, adenina, hipoxantina, inosina e uracila. A partir dos resultados apresentados, pode-se observar, que tanto a exposição gestacional à Cannabis sativa, quanto a exposição da prole na fase adolescente, provocam alterações metabólicas importantes. Os metabólitos significativamente alterados estão envolvidos no ciclo do ácido tricarboxílico, responsável pela respiração mitocondrial, na produção de energia, atuam na biossíntese de aminoácidos, glicólise, estresse oxidativo, podendo alterar o desenvolvimento e maturação do cérebro. Os resultados são preliminares, mas contribuem para o melhor entendimento dos mecanismos toxicológicos envolvidos na exposição crônica causada por essa droga, contribuindo para a prevenção e diagnóstico de danos no desenvolvimento fetal e adolescente. / Metabolomics studies gain importance each day because they help explain biological processes in normal (physiological) or pathological situations. They provide a new insight into the functional impact of environmental gene expression, complementing gene sequencing studies that neglect the impact of environmental exposure on the etiology of diseases. Metabolomics has been applied in toxicology, showing that the comparative metabolic profile of two situations, control and test, can play an important role in the discovery and validation of biomarkers, in addition to contributing to the understanding and interpretation of the toxic action mechanisms of xenobiotics. This research project aims to use a metabolomic approach to evaluate the impact of metabolic changes in the brain of the offspring of mice, which occurred after exposure (via inhalation) to the smoke from the burning Cannabis sativa. Pregnant females were exposed to daily doses of Cannabis sativa or filtered air throughout the gestational period. After birth, male offspring were reached adolescents weaning age were separated from their respective mothers and exposed to Cannabis sativa or to the filtrate for another 60 days. Offspring brain samples were analyzed by gas chromatography coupled to mass spectrometry (GC-MS) in a global metabolomic approach (non-target metabolomics). Metabolic profiles of the exposed animals brains (test group) were compared with those obtained in the control group (non-exposed), and the candidate discriminant metabolites were identified. The metabolites were altered: isoleucine, urea, leucine, GABA, succinic acid, fumaric acid, serine, threonine, creatine, glutamic acid, acetyl aspartic acid, glycerol-1-phosphate, ascorbic acid, tyrosine, citric acid, adenine, hypoxanthine, inosine and uracil were altered. From the results presented, it can be observed that both the gestational exposure in Cannabis sativa and the exposure of the adolescent phase exposure, induced important metabolic alterations. Significantly altered metabolites are involved in the tricarboxylic acid, which are responsible for mitochondrial respiration, in energy production, act at the amino acid biosynthesis, glycolysis, oxidative stress, which may alter the development and maturation of the brain. The results are preliminary but contribute to a better understanding of the mechanisms of toxicity and of fetal and adolescent infection.

Preterm delivery (PTD) is a leading cause of infant death, and surviving infants are at risk for poor health. Data from the Iowa Health in Pregnancy Study, a case-control study of maternal stress on risk of PTD and small for gestational age (SGA) deliveries were used to address three aims: 1) develop a method to correct for error in ultrasound measurement among suspected SGA infants, 2) estimate the association of occupational stress on risk of PTD, and 3) examine injury-related risk factors for PTD. Estimates of gestational age using ultrasound can be biased if the fetus is growth-restricted, yielding underestimates due to the small stature of the fetus. Multivariate linear regression modeling was used to estimate and correct for this bias among subjects with a suspected SGA infant who 1) began prenatal care in the first trimester, 2) reported a last menstrual period and 3) had an ultrasound examination between 7-21 weeks. To correct for this bias, an average of 1.5 weeks was added to the ultrasound gestational age. Following the correction, the proportion of PTD cases decreased from 29.1% to 26.5% while SGA cases increased from 23.7% to 31.3%. Using this PTD classification, occupational physical and psychosocial stressors were studied. Continuous employment over the first 20 weeks of pregnancy was associated with a 30% increased risk of PTD versus not working. Working women reporting highly repetitive tasks (aOR=1.47(1.10-1.98)) or inadequate breaks (aOR=1.67(1.03-2.73)) were at increased risk of PTD. Working women who reported high lifting in the home had double the risk of PTD. Over 5% of control subjects reported an injury during pregnancy, and injured women tended to be younger, unmarried, less educated, and have lower incomes. Women with injuries involving >1 body part (aOR=2.50(1.14-5.49)), or injuries to the abdomen and other regions of the body (OR=1.75(0.59-5.23)) were at increased risk of PTD. Our findings provide a statistical approach to assess and correct for underestimates of ultrasound gestational age in case-control studies of PTD and SGA. The analyses of occupational exposures and injury during pregnancy indicate the need for studies that incorporate specific and standardized assessments of these exposures.