<p>This secondary analysis aimed to develop dietary scores to assess the dietary intake of pregnant women in the West Coast/ Winelands region and determine the association with LBW. Further to determine the association between the dietary scores and maternal socioeconomic and socio-demographic characteristics and maternal smoking and/or alcohol consumption during pregnancy.</p>

A world-wide series of epidemiological studies has demonstrated that there is an association between being born small and the risk of visceral obesity, a more central deposition of subcutaneous fat and insulin resistance in adult life. In the lamb, intrauterine growth restriction (IUGR) results in a low birth weight and an increased visceral fat mass by 45d of postnatal life. In this thesis I have investigated the effect of IUGR on adipose tissue development and function during fetal and early postnatal life in the sheep. IUGR was induced by removal of the majority of endometrial caruncles in non pregnant ewes prior to mating which resulted in the subsequent placental restriction of fetal growth (PR). Fetal blood samples were collected from 116d gestation and visceral perirenal adipose tissue (PAT) collected from PR and control fetuses at 145d. In lambs IUGR was defined as a birth weight less than 2 standard deviations below the mean of a cohort of singleton Merino lambs. Blood samples were collected throughout the first 3 weeks of life and PAT and subcutaneous adipose tissue (SAT) was collected at 21 d. It was determined whether IUGR alters the expression of genes which regulate adipogenesis (IGF1, IGFR1, IGF2, IGFR2, PPARy, and RXRα), adipocyte metabolism (LPL, G3PDH, GAPDH) and adipokine signalling (leptin, adiponectin) in adipose tissue depots before and after birth using qRT-PCR. PR fetuses were hypoglycaemic, hypoinsulinaemic, hypoxic, and had a lower body weight than Control fetuses. The expression of both IGF1 and leptin mRNA in PAT, the major fetal adipose depot, was lower in the PR fetuses, although there was no difference in the expression of other adipokine or adipogenic genes in PAT between PR and control fetuses. Thus restriction of placental and hence fetal substrate supply results in decreased IGF1 and leptin expression in fetal visceral adipose tissue which may alter the functional development of the perirenal fat depot and contribute to altered leptin signalling in the growth restricted newborn and the subsequent emergence of an increased visceral adiposity. At 21d of postnatal life there was no increase in the relative mass of perirenal or subcutaneous fat in IUGR lambs compared with controls. Thus, this study has investigated the effect of IUGR on the development of adipose tissue prior to the development of an obese phenotype. At 21d of life there was a sex specific effect of IUGR on the expression of PPARy and leptin mRNA in perirenal visceral fat such that PPARy and leptin mRNA expression was decreased in male IUGR lambs, but not females. Interestingly PAT mass was greater in females than males, independent of birth weight. Plasma insulin concentrations during the first 24h after birth predicted the size of the adipocytes and expression of adiponectin in visceral adipose tissue in both males and females at 21d. Thus, the nutritional environment before, and immediately after birth, may program adipocyte growth and gene expression in visceral adipose tissue. The differential effect of sex and birth weight on PPARy and leptin expression in visceral fat may be important in the subsequent development of visceral obesity and the insulin resistant phenotype in later life. At 21d of life there was no difference between Control and IUGR lambs in the relative mass of subcutaneous fat, or the expression of PPARy, RXRα, leptin, adiponectin, LPL, G3PDH, and GAPDH in subcutaneous fat at 21d of life. We have shown that the growth of the subcutaneous fat depot is related to plasma glucose, insulin and leptin concentrations, and to the development of perirenal fat. Thus, in contrast to perirenal adipose tissue, the postnatal, but not the fetal nutritional environment, programs subcutaneous adipocyte growth and gene expression. This thesis speculates that there may be a factor secreted from visceral fat that influences the development of the subcutaneous fat depot. At 21d of life there was also an effect of sex, but not IUGR, on the expression of IGF mRNA in adipose tissue. Male lambs had a higher expression of IGF1 mRNA in both PAT and SAT, and a higher expression of IGF1R and IGF2R in SAT compared with female lambs. It is likely that these differences in IGF mRNA levels reflect sexual dimorphism of the GH-IGF axis. When male and female lambs were combined there was a higher expression of IGF1 mRNA in SAT compared with PAT, and a higher expression of IGF2, IGF1R and IGF2R mRNA in PAT compared with SAT. These differences in IGF mRNA expression provide a potential mechanism to explain the sex and depot specific variations in mitogenic potency of IGF1 and proliferative capacities of preadipocytes, the regional variation in adipocyte metabolism, and the difference in incidence of visceral obesity between men and women in adult life. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1347421 / Thesis (Ph.D.) - University of Adelaide, School of Molecular and Biomedical Science, 2008

A world-wide series of epidemiological studies has demonstrated that there is an association between being born small and the risk of visceral obesity, a more central deposition of subcutaneous fat and insulin resistance in adult life. In the lamb, intrauterine growth restriction (IUGR) results in a low birth weight and an increased visceral fat mass by 45d of postnatal life. In this thesis I have investigated the effect of IUGR on adipose tissue development and function during fetal and early postnatal life in the sheep. IUGR was induced by removal of the majority of endometrial caruncles in non pregnant ewes prior to mating which resulted in the subsequent placental restriction of fetal growth (PR). Fetal blood samples were collected from 116d gestation and visceral perirenal adipose tissue (PAT) collected from PR and control fetuses at 145d. In lambs IUGR was defined as a birth weight less than 2 standard deviations below the mean of a cohort of singleton Merino lambs. Blood samples were collected throughout the first 3 weeks of life and PAT and subcutaneous adipose tissue (SAT) was collected at 21 d. It was determined whether IUGR alters the expression of genes which regulate adipogenesis (IGF1, IGFR1, IGF2, IGFR2, PPARy, and RXRα), adipocyte metabolism (LPL, G3PDH, GAPDH) and adipokine signalling (leptin, adiponectin) in adipose tissue depots before and after birth using qRT-PCR. PR fetuses were hypoglycaemic, hypoinsulinaemic, hypoxic, and had a lower body weight than Control fetuses. The expression of both IGF1 and leptin mRNA in PAT, the major fetal adipose depot, was lower in the PR fetuses, although there was no difference in the expression of other adipokine or adipogenic genes in PAT between PR and control fetuses. Thus restriction of placental and hence fetal substrate supply results in decreased IGF1 and leptin expression in fetal visceral adipose tissue which may alter the functional development of the perirenal fat depot and contribute to altered leptin signalling in the growth restricted newborn and the subsequent emergence of an increased visceral adiposity. At 21d of postnatal life there was no increase in the relative mass of perirenal or subcutaneous fat in IUGR lambs compared with controls. Thus, this study has investigated the effect of IUGR on the development of adipose tissue prior to the development of an obese phenotype. At 21d of life there was a sex specific effect of IUGR on the expression of PPARy and leptin mRNA in perirenal visceral fat such that PPARy and leptin mRNA expression was decreased in male IUGR lambs, but not females. Interestingly PAT mass was greater in females than males, independent of birth weight. Plasma insulin concentrations during the first 24h after birth predicted the size of the adipocytes and expression of adiponectin in visceral adipose tissue in both males and females at 21d. Thus, the nutritional environment before, and immediately after birth, may program adipocyte growth and gene expression in visceral adipose tissue. The differential effect of sex and birth weight on PPARy and leptin expression in visceral fat may be important in the subsequent development of visceral obesity and the insulin resistant phenotype in later life. At 21d of life there was no difference between Control and IUGR lambs in the relative mass of subcutaneous fat, or the expression of PPARy, RXRα, leptin, adiponectin, LPL, G3PDH, and GAPDH in subcutaneous fat at 21d of life. We have shown that the growth of the subcutaneous fat depot is related to plasma glucose, insulin and leptin concentrations, and to the development of perirenal fat. Thus, in contrast to perirenal adipose tissue, the postnatal, but not the fetal nutritional environment, programs subcutaneous adipocyte growth and gene expression. This thesis speculates that there may be a factor secreted from visceral fat that influences the development of the subcutaneous fat depot. At 21d of life there was also an effect of sex, but not IUGR, on the expression of IGF mRNA in adipose tissue. Male lambs had a higher expression of IGF1 mRNA in both PAT and SAT, and a higher expression of IGF1R and IGF2R in SAT compared with female lambs. It is likely that these differences in IGF mRNA levels reflect sexual dimorphism of the GH-IGF axis. When male and female lambs were combined there was a higher expression of IGF1 mRNA in SAT compared with PAT, and a higher expression of IGF2, IGF1R and IGF2R mRNA in PAT compared with SAT. These differences in IGF mRNA expression provide a potential mechanism to explain the sex and depot specific variations in mitogenic potency of IGF1 and proliferative capacities of preadipocytes, the regional variation in adipocyte metabolism, and the difference in incidence of visceral obesity between men and women in adult life. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1347421 / Thesis (Ph.D.) - University of Adelaide, School of Molecular and Biomedical Science, 2008

Submitted by LUIZA TAVARES CARNEIRO SANTIAGO null (luiza_tcs@hotmail.com) on 2016-05-23T14:20:11Z No. of bitstreams: 1 Dissertação Mestrado - Luiza Tavares Carneiro Santiago.pdf: 1233741 bytes, checksum: bb457286bd0f32f04ccc8f34ad966dc1 (MD5) / Approved for entry into archive by Felipe Augusto Arakaki (arakaki@reitoria.unesp.br) on 2016-05-24T12:46:40Z (GMT) No. of bitstreams: 1 santiago_ltc_me_bot.pdf: 1233741 bytes, checksum: bb457286bd0f32f04ccc8f34ad966dc1 (MD5) / Made available in DSpace on 2016-05-24T12:46:40Z (GMT). No. of bitstreams: 1 santiago_ltc_me_bot.pdf: 1233741 bytes, checksum: bb457286bd0f32f04ccc8f34ad966dc1 (MD5) Previous issue date: 2016-02-29 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / INTRODUÇÃO: O efeito da idade gestacional e do crescimento fetal nos imunocomponentes do leite materno ainda é pouco conhecido. OBJETIVO: Determinar a quantidade de citocinas no colostro em função da idade gestacional e do crescimento fetal. MÉTODO: Estudo transversal, envolvendo mães de recém-nascidos prematuros (PT) e de termo (T), nascidos na Maternidade da Faculdade de Medicina de Botucatu – UNESP, em 2014-2015. Critério de inclusão: gestação única; ausência de diabetes materno, ou uso de medicações/drogas ilícitas, sorologias negativas; recém-nascido com peso adequado (AIG) ou pequeno para idade gestacional (PIG) e sem malformação. Excluídos: não obtenção do colostro, mastite, uso de medicamento pela puérpera. Foram estudados 4 grupos: PT-PIG (n=18), PT-AIG (n=42), T-PIG (n=45), T-AIG (controle, n=42). No colostro coletado entre 24-72 horas pós-nascimento, foram dosadas as citocinas (IL-1β, IL-6, IL-8, IL-10, IL-12 e TNF-α) por citometria de fluxo. Na comparação entre grupos utilizou-se o Qui-quadrado ou teste Exato de Fisher, ANOVA, e Correlação de Pearson. RESULTADOS: As características maternas foram semelhantes nos 4 grupos. A idade gestacional média foi 34 semanas nos prematuros e 39 semanas nos termos. Os níveis de citocinas do colostro não diferiram entre os grupos de termo e pretermo. O grupo T-PIG apresentou maior quantidade de citocinas comparado aos demais. Nos 4 grupos houve correlação entre as citocinas, especialmente nos T-PIG. CONCLUSÃO: A quantidade de citocinas no colostro foi influenciada pelo crescimento fetal e não pela idade gestacional. / INTRODUCTION: The effect of gestational age and foetal growth in the imunno componentes of human milk is not well stablished. OBJECTIVE: To determine cytokines levels in colostrum according to gestational age and foetal growth. METHOD: Cross-sectional study with mothers of term (T) and preterm (PT) infants, with birth weight appropriate-for-gestational age (AGA) and small-for-gestational age (SGA), born at the Maternity of Botucatu School of Medicine- UNESP, during 2014 -2015. Inclusion criteria were: single gestation; absence of diabetes mellitus; no maternal use of medications or illicit drugs; negative maternal serology; and newborn without malformation. Mothers with mastitis, or use of medication, or failure to obtain colostrum, were excluded. Four groups were studied: PT-SGA (n=18), PT-AGA (n=42), T-SGA (n=45), and T-AGA (control, n=42). Colostrum was collected between 24-72 hours after birth, and cytokines (IL-1β, IL-6, IL-8, IL-10, IL-12 and TNF-α) were measured by flow cytometry. Chi-square or Fisher's exact test, ANOVA and Pearson's correlation were used to evaluate differences among the groups. RESULTS: Maternal characteristics did not differ between groups. The mean gestational age was 34 and 39 weeks for preterm and term groups. Cytokines levels in the colostrum were not different between term and preterm groups. However cytokines levels were significantly higher in colostrum from mothers of T-SGA. A positive correlation between cytokines was found in all groups, especially in T-SGA. CONCLUSION: Cytokines levels in colostrum was influenced by foetal growth, while the correlation between cytokines varied according to gestational age and foetal growth. / FAPESP: 2014/12784-9

Com o objetivo de comparar a orientação visual e auditiva no período neonatal imediato entre recém-nascidos (RNs) a termo pequenos para idade gestacional (PIGs) com os de peso adequado (AIGs), assim como o seu custo para os bebês, foi estudada uma população de RNs sadios, dividida em dois grupos. Pacientes e Métodos: nós conduzimos um estudo transversal controlado, onde fator de exposição foi o retardo de crescimento intra-uterino (RCIU) e os desfechos foram os comportamentos de orientação visual e auditiva dos bebês, bem como o custo para sua realização ( itens suplementares). O exame completo foi realizado (EACN) mas neste momento enfatizamos para estudo os comportamentos de orientação e seu custo para o bebê. O grupo 1 foi constituído por 56 RNs PIGs e o grupo 2 por 118 RNs AIGs. O instrumento utilizado foi a Escala de Avaliação do Comportamento Neonatal (EACN) de Brazelton e o exame ocorreu entre 48 e 72 horas após o nascimento. Para minimizar os efeitos de drogas usadas em analgesia obstétrica com impacto no comportamento neonatal, só foram incluídos no estudo, bebês cujas mães tenham recebido, no máximo, bloqueio peri-dural com marcaína. Foram excluídos os malformados, aqueles cujas mães não realizaram prénatal, os RNs PIG simétricos, os que necessitaram cuidados intensivos e aqueles cujas mães tinham antecedentes de uso de outras drogas, que não tabaco. Além dos ítens de orientação e o custo dela para o RN, outras variáveis incluíram: a idade materna, paridade, tipo de parto, Apgar a 1 e 5 minutos, idade gestacional, sexo, cor, peso, comprimento e perímetro cefálico do RN, e a prevalência de aleitamento materno. Para a análise estatística, os dados foram descritos pela média e desvio-padrão e as comparações entre os grupos foram feitas através do teste t para amostras independentes. Para a avaliação da magnitude das diferenças, foi calculado o tamanho de efeito padronizado (TEP). Resultados: Não foram encontradas diferenças significativas quanto à idade materna, paridade, Apgar no primeiro e quinto minutos, idade gestacional, sexo dos bebês, cor e tipo de alimentação. No entanto, elas foram encontradas para o peso de nascimento, comprimento e perímetro cefálico. Os comportamentos de resposta aos itens de orientação aos estímulos animados e inanimados, visuais e auditivos, foram significativamente diferentes entre os grupos, assim como os itens suplementares. Discussão: os achados deste estudo suportam a idéia de que os RNs PIGs apresentam respostas de menor qualidade aos estímulos de orientação visual e auditiva, tanto animados como inanimados do que os bebês AIG no período pós-parto imediato. Nossos resultados confirmam observações de estudos anteriores de que essas diferenças são encontradas no grupo de orientação como um todo. Em nosso estudo, porém, diferentemente dos estudos prévios, encontramos significância comparando-se os comportamentos de resposta a cada um dos ítens do comportamento social. As significativas diferenças encontradas nos ítens suplementares, reforçam a idéia de que os bebês PIG se constituem em um grupo de risco para a interação com o seu meio ambiente. / In order to compare the behavior of visual and auditive orientation in the imediate neonatal period between fullterm, small for gestational age (SGA) to those of adequate weight to gestational age (AGA), we studied 174 healthy neonates, divided in two groups. Subjects and Methods: we conducted a controlled, cross-sectional study, where the exposure factor was the intrauterine growth retardation (IUGR) and the endpoints were the babie’s visual and auditive orientation behaviors, as well as the cost to it (supplementary itens). The complete NBAS was performed but at this moment we enfasize the orientation behavior and supplementary itens to study. Group 1 was made by 56 SGA babies and group 2 by 118 AGA neonates. As instrument, we used the Brazelton's Neonatal Behavior Assessment Scale (NBAS) and the exam ocurred between 48 and 72 hours after birth. With the goal of minimize the effects of drugs used for obstetric analgesia in the neonatal behavior, only babies whose mothers received no more than epidural blockage with marcaíne were included in the study. We excluded children with malformations, those who required intensive care, those whose mothers has no prenatal care, the simetric SGA babies, as well as those whose mother received medication other than marcaíne or used drugs, except tobaco. We looked at the baby's orientation behavior as well as the cost to it. Other studied variables were: maternal age, parity, type of delivery, Apgar score at 1 and 5 minutes, gestational age, and baby's colour, gender, weight, lenght, cephalic perimeter and prevalence of breastfeeding. Statistical analysis was carried out after treating data by the mean and standard-deviation and comparisons between groups were made using the t test. To evaluate the magnitude of the differences, we calculated the Cohen's Effect Sizes. Results: we weren't able to find any significant difference between groups regarding maternal age, parity, Apgar scores, gestational age as well as babie's colour, gender or breasfeeding. However, we found significant differences in birth weight, as expected due to the study design. And also, in lenght and cephalic perimeter. Orientation behavior, that is, response to animated and inanimated visual and auditory stimulous was significantly different between groups, as well as the behavior in the supplementary itens. Discussion: our results support the idea that SGA babies perform poorly than their AGA pairs in the NBAS orientation group as a whole. And also, that they need more support from the examiner. This has allready been reported by others. However, in this study, differently than others, AGA babies behaved better than SGA newborns in every item of the orientation exam. The significant differences found in the supplementary itens support the idea that SGA babies represent a risk group for interaction with their caretakers.

Com o objetivo de comparar a orientação visual e auditiva no período neonatal imediato entre recém-nascidos (RNs) a termo pequenos para idade gestacional (PIGs) com os de peso adequado (AIGs), assim como o seu custo para os bebês, foi estudada uma população de RNs sadios, dividida em dois grupos. Pacientes e Métodos: nós conduzimos um estudo transversal controlado, onde fator de exposição foi o retardo de crescimento intra-uterino (RCIU) e os desfechos foram os comportamentos de orientação visual e auditiva dos bebês, bem como o custo para sua realização ( itens suplementares). O exame completo foi realizado (EACN) mas neste momento enfatizamos para estudo os comportamentos de orientação e seu custo para o bebê. O grupo 1 foi constituído por 56 RNs PIGs e o grupo 2 por 118 RNs AIGs. O instrumento utilizado foi a Escala de Avaliação do Comportamento Neonatal (EACN) de Brazelton e o exame ocorreu entre 48 e 72 horas após o nascimento. Para minimizar os efeitos de drogas usadas em analgesia obstétrica com impacto no comportamento neonatal, só foram incluídos no estudo, bebês cujas mães tenham recebido, no máximo, bloqueio peri-dural com marcaína. Foram excluídos os malformados, aqueles cujas mães não realizaram prénatal, os RNs PIG simétricos, os que necessitaram cuidados intensivos e aqueles cujas mães tinham antecedentes de uso de outras drogas, que não tabaco. Além dos ítens de orientação e o custo dela para o RN, outras variáveis incluíram: a idade materna, paridade, tipo de parto, Apgar a 1 e 5 minutos, idade gestacional, sexo, cor, peso, comprimento e perímetro cefálico do RN, e a prevalência de aleitamento materno. Para a análise estatística, os dados foram descritos pela média e desvio-padrão e as comparações entre os grupos foram feitas através do teste t para amostras independentes. Para a avaliação da magnitude das diferenças, foi calculado o tamanho de efeito padronizado (TEP). Resultados: Não foram encontradas diferenças significativas quanto à idade materna, paridade, Apgar no primeiro e quinto minutos, idade gestacional, sexo dos bebês, cor e tipo de alimentação. No entanto, elas foram encontradas para o peso de nascimento, comprimento e perímetro cefálico. Os comportamentos de resposta aos itens de orientação aos estímulos animados e inanimados, visuais e auditivos, foram significativamente diferentes entre os grupos, assim como os itens suplementares. Discussão: os achados deste estudo suportam a idéia de que os RNs PIGs apresentam respostas de menor qualidade aos estímulos de orientação visual e auditiva, tanto animados como inanimados do que os bebês AIG no período pós-parto imediato. Nossos resultados confirmam observações de estudos anteriores de que essas diferenças são encontradas no grupo de orientação como um todo. Em nosso estudo, porém, diferentemente dos estudos prévios, encontramos significância comparando-se os comportamentos de resposta a cada um dos ítens do comportamento social. As significativas diferenças encontradas nos ítens suplementares, reforçam a idéia de que os bebês PIG se constituem em um grupo de risco para a interação com o seu meio ambiente. / In order to compare the behavior of visual and auditive orientation in the imediate neonatal period between fullterm, small for gestational age (SGA) to those of adequate weight to gestational age (AGA), we studied 174 healthy neonates, divided in two groups. Subjects and Methods: we conducted a controlled, cross-sectional study, where the exposure factor was the intrauterine growth retardation (IUGR) and the endpoints were the babie’s visual and auditive orientation behaviors, as well as the cost to it (supplementary itens). The complete NBAS was performed but at this moment we enfasize the orientation behavior and supplementary itens to study. Group 1 was made by 56 SGA babies and group 2 by 118 AGA neonates. As instrument, we used the Brazelton's Neonatal Behavior Assessment Scale (NBAS) and the exam ocurred between 48 and 72 hours after birth. With the goal of minimize the effects of drugs used for obstetric analgesia in the neonatal behavior, only babies whose mothers received no more than epidural blockage with marcaíne were included in the study. We excluded children with malformations, those who required intensive care, those whose mothers has no prenatal care, the simetric SGA babies, as well as those whose mother received medication other than marcaíne or used drugs, except tobaco. We looked at the baby's orientation behavior as well as the cost to it. Other studied variables were: maternal age, parity, type of delivery, Apgar score at 1 and 5 minutes, gestational age, and baby's colour, gender, weight, lenght, cephalic perimeter and prevalence of breastfeeding. Statistical analysis was carried out after treating data by the mean and standard-deviation and comparisons between groups were made using the t test. To evaluate the magnitude of the differences, we calculated the Cohen's Effect Sizes. Results: we weren't able to find any significant difference between groups regarding maternal age, parity, Apgar scores, gestational age as well as babie's colour, gender or breasfeeding. However, we found significant differences in birth weight, as expected due to the study design. And also, in lenght and cephalic perimeter. Orientation behavior, that is, response to animated and inanimated visual and auditory stimulous was significantly different between groups, as well as the behavior in the supplementary itens. Discussion: our results support the idea that SGA babies perform poorly than their AGA pairs in the NBAS orientation group as a whole. And also, that they need more support from the examiner. This has allready been reported by others. However, in this study, differently than others, AGA babies behaved better than SGA newborns in every item of the orientation exam. The significant differences found in the supplementary itens support the idea that SGA babies represent a risk group for interaction with their caretakers.

Com o objetivo de comparar a orientação visual e auditiva no período neonatal imediato entre recém-nascidos (RNs) a termo pequenos para idade gestacional (PIGs) com os de peso adequado (AIGs), assim como o seu custo para os bebês, foi estudada uma população de RNs sadios, dividida em dois grupos. Pacientes e Métodos: nós conduzimos um estudo transversal controlado, onde fator de exposição foi o retardo de crescimento intra-uterino (RCIU) e os desfechos foram os comportamentos de orientação visual e auditiva dos bebês, bem como o custo para sua realização ( itens suplementares). O exame completo foi realizado (EACN) mas neste momento enfatizamos para estudo os comportamentos de orientação e seu custo para o bebê. O grupo 1 foi constituído por 56 RNs PIGs e o grupo 2 por 118 RNs AIGs. O instrumento utilizado foi a Escala de Avaliação do Comportamento Neonatal (EACN) de Brazelton e o exame ocorreu entre 48 e 72 horas após o nascimento. Para minimizar os efeitos de drogas usadas em analgesia obstétrica com impacto no comportamento neonatal, só foram incluídos no estudo, bebês cujas mães tenham recebido, no máximo, bloqueio peri-dural com marcaína. Foram excluídos os malformados, aqueles cujas mães não realizaram prénatal, os RNs PIG simétricos, os que necessitaram cuidados intensivos e aqueles cujas mães tinham antecedentes de uso de outras drogas, que não tabaco. Além dos ítens de orientação e o custo dela para o RN, outras variáveis incluíram: a idade materna, paridade, tipo de parto, Apgar a 1 e 5 minutos, idade gestacional, sexo, cor, peso, comprimento e perímetro cefálico do RN, e a prevalência de aleitamento materno. Para a análise estatística, os dados foram descritos pela média e desvio-padrão e as comparações entre os grupos foram feitas através do teste t para amostras independentes. Para a avaliação da magnitude das diferenças, foi calculado o tamanho de efeito padronizado (TEP). Resultados: Não foram encontradas diferenças significativas quanto à idade materna, paridade, Apgar no primeiro e quinto minutos, idade gestacional, sexo dos bebês, cor e tipo de alimentação. No entanto, elas foram encontradas para o peso de nascimento, comprimento e perímetro cefálico. Os comportamentos de resposta aos itens de orientação aos estímulos animados e inanimados, visuais e auditivos, foram significativamente diferentes entre os grupos, assim como os itens suplementares. Discussão: os achados deste estudo suportam a idéia de que os RNs PIGs apresentam respostas de menor qualidade aos estímulos de orientação visual e auditiva, tanto animados como inanimados do que os bebês AIG no período pós-parto imediato. Nossos resultados confirmam observações de estudos anteriores de que essas diferenças são encontradas no grupo de orientação como um todo. Em nosso estudo, porém, diferentemente dos estudos prévios, encontramos significância comparando-se os comportamentos de resposta a cada um dos ítens do comportamento social. As significativas diferenças encontradas nos ítens suplementares, reforçam a idéia de que os bebês PIG se constituem em um grupo de risco para a interação com o seu meio ambiente. / In order to compare the behavior of visual and auditive orientation in the imediate neonatal period between fullterm, small for gestational age (SGA) to those of adequate weight to gestational age (AGA), we studied 174 healthy neonates, divided in two groups. Subjects and Methods: we conducted a controlled, cross-sectional study, where the exposure factor was the intrauterine growth retardation (IUGR) and the endpoints were the babie’s visual and auditive orientation behaviors, as well as the cost to it (supplementary itens). The complete NBAS was performed but at this moment we enfasize the orientation behavior and supplementary itens to study. Group 1 was made by 56 SGA babies and group 2 by 118 AGA neonates. As instrument, we used the Brazelton's Neonatal Behavior Assessment Scale (NBAS) and the exam ocurred between 48 and 72 hours after birth. With the goal of minimize the effects of drugs used for obstetric analgesia in the neonatal behavior, only babies whose mothers received no more than epidural blockage with marcaíne were included in the study. We excluded children with malformations, those who required intensive care, those whose mothers has no prenatal care, the simetric SGA babies, as well as those whose mother received medication other than marcaíne or used drugs, except tobaco. We looked at the baby's orientation behavior as well as the cost to it. Other studied variables were: maternal age, parity, type of delivery, Apgar score at 1 and 5 minutes, gestational age, and baby's colour, gender, weight, lenght, cephalic perimeter and prevalence of breastfeeding. Statistical analysis was carried out after treating data by the mean and standard-deviation and comparisons between groups were made using the t test. To evaluate the magnitude of the differences, we calculated the Cohen's Effect Sizes. Results: we weren't able to find any significant difference between groups regarding maternal age, parity, Apgar scores, gestational age as well as babie's colour, gender or breasfeeding. However, we found significant differences in birth weight, as expected due to the study design. And also, in lenght and cephalic perimeter. Orientation behavior, that is, response to animated and inanimated visual and auditory stimulous was significantly different between groups, as well as the behavior in the supplementary itens. Discussion: our results support the idea that SGA babies perform poorly than their AGA pairs in the NBAS orientation group as a whole. And also, that they need more support from the examiner. This has allready been reported by others. However, in this study, differently than others, AGA babies behaved better than SGA newborns in every item of the orientation exam. The significant differences found in the supplementary itens support the idea that SGA babies represent a risk group for interaction with their caretakers.

Orientadores: José Antônio Rocha Gontijo, Flávia Fernandes Mesquita / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-25T07:43:12Z (GMT). No. of bitstreams: 1 Canale_Vinicius_M.pdf: 2382904 bytes, checksum: bf0d6a9b4243b86411026cd098372cc8 (MD5) Previous issue date: 2014 / Resumo: Já está bem documentado que a dieta hipoproteica em ratos durante a gestação produz efeitos no crescimento fetal, uma persistente elevação na pressão arterial e disfunções no desenvolvimento renal da prole. Alterações na pressão arterial parecem estar relacionadas à acentuada redução no número de nefros que acaba por causar um quadro de hipertrofia e hiperfluxo nos nefros remanescentes como adaptação para equilibrar a taxa de filtração, no entanto, os mecanismos utilizados para esta adaptação culminam com o surgimento de albuminúria. Este processo acaba por causar esclerose glomerular culminando em um ciclo, comprometendo cada vez mais os nefros remanescentes. O desenvolvimento deste quadro pode levar à síndrome nefrótica e posteriormente à doença renal terminal. Acredita-se que o principal fator atuante na programação fetal neste modelo é devido à exposição exacerbada do feto aos glicocorticoides materno, o que acaba por comprometer a correto desenvolvimento e diferenciação de tecidos e órgãos, e na expressão ou atividade de uma série de receptores e enzimas. Recentemente, tem surgido a hipótese de que a atividade da mTORC poderia estar envolvida no surgimento de doenças na idade adulta neste modelo experimental. Este trabalho teve por objetivo avaliar se a inibição da mTORC através do tratamento com rapamicina em animais programados poderia ser benéfico, inibindo o surgimento de complicações relacionadas com a estrutura glomerular e como seria seu efeitos sistêmico, sobre a função renal e pressão arterial sistêmica. Ratos Wistar receberam ração com baixa proteína (6% LP) e dieta controle (17% NP) durante o período gestacional. A prole de machos foi tratada com rapamicina diluída em DMSO (5%) e administrada via intraperitoneal na dose de 1mg/kg, 3 vezes por semana, a partir da 4ª semana de vida até a 12ª semana. A aferição da pressão arterial sistólica foi realizada nas idades 8, 12 e 16. Foi observado que nos grupos que receberam rapamicina, a pressão artéria sistólica elevou-se consideravelmente em todas as idades. A avaliação da função renal foi realizada através de clearance de creatinina e lítio nas mesmas idades e observamos que durante todo o tratamento, o grupo NP que recebeu rapamicina excretou mais sódio, na porção pós-proximal do túbulo. Além disso, não houve diferença na taxa da filtração glomerular em nenhuma das idades. Quando a proteinúria foi avaliada, observamos que o grupo programado LP sem rapamicina, apresentou evolução com o passar das semanas sendo significativamente maior a partir das 12ª e 16ª semanas, no entanto, os grupos que receberam rapamicina, não apresentaram a mesma evolução, indicando preservação da estrutura glomerular. Os presentes resultados demonstram que apesar de a rapamicina ter elevado a pressão arterial em ambos os grupos, há uma indicação de que os animais programados tem um controle menos eficaz no controle da pressão arterial através da função renal. Mesmo diante da pressão elevada, a rapamicina foi capaz de inibir injúrias à barreira de filtração / Abstract: It is well established that a low protein diet in rats during pregnancy causes effects on fetal growth, a persistent elevation in blood pressure and renal dysfunction in the offspring at a later age. Alterations in blood pressure seem to be related to the marked reduction in the number of nephrons which ultimately causes an overflow and hypertrophy in the remaining nephrons in the attempt to adapt its balance on the filtration rate. However, the mechanisms used for this adaptation results in the appearance of albuminuria. This process might cause glomerular sclerosis culminating in a cycle, increasing the damage to the remaining nephrons. The development of this framework can lead to nephrotic syndrome and subsequently to ESRD. It is believed that the main factor in the fetal programming model is the fetus overexposure to maternal glucocorticoids, which ultimately compromises the proper development and differentiation of tissues and organs. Additionally, the expression and the activity of a number of receptors and enzymes is also affected. Recently, in this experimental model, there has arisen the hypothesis that the activity of mTORC could be involved in the onset of disease in adulthood. This study assess whether the inhibition of mTORC, through the treatment with rapamycin in programmed animals, could be beneficial by inhibiting the onset complications related to glomerular structure and its affect on renal function and blood pressure. Wistar female rats were fed with low protein (6 % LP) or control diet (17 % NP) during pregnancy. The male offspring were treated with rapamycin diluted in DMSO (5 %) and administered intraperitoneally at a dose of 1mg/kg, 3 times per week, from the 4th week of life until the 12th week. The measurement of systolic blood pressure was measured at 8, 12, and 16 weeks old. We noticed that in the groups treated with rapamycin the arterial systolic pressure rose considerably in all ages. The assessment of renal function was performed by creatinine clearance and lithium at the same ages as the blood pressures assessment. The NPR group that received rapamycin had an increase in sodium excretion at the post- proximal tubule during the whole treatment. Additionally, there was no difference in the rate of glomerular filtration rate at any age among the groups. When proteinuria was assessed, we found that the programmed Group LP without rapamycin, showed an increase along the weeks and as expected, the groups that have received rapamycin did not show the same trend, indicating preservation in the glomerular structure. The present results demonstrate that rapamycin caused increase in the blood pressure in both groups however, it was able still to inhibit the injury into the filtration barrier. Additionally, there is an indication that the programmed animals, has a less effective control in the blood pressure and the excretion of sodium, even when the treatment is interrupted / Mestrado / Fisiopatologia Médica / Mestre em Ciências

Magister Scientiae - MSc / This secondary analysis aimed to develop dietary scores to assess the dietary intake of pregnant women in the West Coast/ Winelands region and determine the association with LBW. Further to determine the association between the dietary scores and maternal socioeconomic and socio-demographic characteristics and maternal smoking and/or alcohol consumption during pregnancy. / South Africa

Résumé : Le sFlt1 semble être un bon marqueur de la prééclampsie (PE). Nous avons évalué dans le cadre d’un essai randomisé contrôlé (MOMA), l’impact sur l’issue de grossesse d’un suivi rapproché de femmes identifiées comme « à risque » par un taux élevé de sFlt1 plasmatique entre 24 et 29 SA. Dans cet essai 939 nullipares ont été incluses en 2 bras (sflt1 connu ou non connu). Nos résultats ne montrent pas d’amélioration de l’issue de grossesse et suggèrent que l’inefficience de l’intervention (suivi rapproché) en est la cause la plus probable. Aussi la mesure du sFlt1 pour prédire la survenue d'une PE ne semble pas utile tant qu’un traitement efficace n’est pas à disposition. Des anomalies de la stéroïdogénèse placentaire ont été retrouvées associées à la PE. 90 échantillons issus de la cohorte MOMA répartis en trois groupes (25 PE, 25 retard de croissance intra utérin (RCIU) sans PE et 40 contrôles) ont été utilisés pour évaluer le profil stéroïdes par la technique fiable de GC/MS (entre 24 et 29 SA) - soit avant les signes cliniques -. Nous avons mis en évidence dans le groupe PE un défaut d'aromatisation des androgènes par le calcul du ratio estradiol/Δ4-Dione (sang) et un défaut d’expression de l’aromatase (placenta). Tout comme les taux significativement bas de sulfate de prégnénolone retrouvés, ce défaut d’aromatisation semble spécifique de la PE car ils n’ont pas été observés dans le groupe RCIU. Ces modifications s'inscrivent dans une dérégulation du profil stéroïdien global. Nous avons en effet observé dans les groupes PE et RCIU, un excés de 20α-dihydro-progestérone (20α-DHP) et un ratio 20α-DHP/Progestérone significativement élevé. Les stéroïdes sexuels partagent des voies de signalisation communes avec les facteurs angiogéniques, faisant inscrire aisément l’hypothèse « anomalies de la stéroïdogénèse » dans les concepts actuels de la physiopathologie de la PE. Les liens entre perturbations de la stéroïdogénèse et la prééclampsie sont discutés. / Abstract : sFlt1 appears to be a good biomarker of preeclampsia (PE). The impact on pregnancy outcomes of close monitoring of women identified as "at risk" at 24 and 29 weeks of gestation (weeks) by a high level of plasma sFlt1, was evaluated in a randomized controlled trial (MOMA). 939 nulliparous women were included in 2 arms (sFlt1 known or unknown). Our results do not show any improvement of pregnancy outcomes and suggest that the inefficiency of the intervention (close follow-up) is the most likely cause. Thus, routine sFlt1 screening to predict the occurrence of PE does not seem useful until effective treatment is available. Abnormalities of placental steroidogenesis have been associated with PE. 90 samples from the MOMA cohort divided into three groups (25 intra-uterine growth retardation (IUGR) without PE, 25 PE and 40 controls) were used to assess by the reliable GC / MS technique, the steroid profile (between 24 and 29 weeks)before the development of clinical signs. In the PE group, we showed abnormal androgen aromatization, by calculating the estradiol/Δ4-Dione ratio (blood), and a lack of expression of placental aromatase. Similarly to the significantly low levels of pregnenolone sulfate found, this lack of aromatization seems specific to PE as they are not found in the IUGR group. These modifications are part of a deregulation of the overall steroid profile. In the PE and IUGR groups, we observed an excess of 20α-dihydroprogesterone (20α-DHP) and a significantly high 20α-DHP/Progesterone ratio. Sex steroids share common signaling pathways with angiogenic factors which easily integrate the "steroidogenesis abnormalities" hypothesis in the current concepts in the pathophysiology of PE. Links between disturbances of steroidogenesis and preeclampsia are discussed.