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Orientadores: Cleisson Fabio Andrioli Peralta, Ricardo Barini / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-11-27T11:44:05Z (GMT). No. of bitstreams: 1 BenniniJunior_JoaoRenato_M.pdf: 1809698 bytes, checksum: 399e6ab502353af527e35953428d5e09 (MD5) Previous issue date: 2009 / Resumo: Introdução: Alguns estudos demonstram que a predição do peso fetal usando a volumetria dos membros fetais é mais precisa do que quando se usam medidas bidimensionais (2D). Até hoje, somente o método multiplanar foi utilizado para a volumetria dos membros fetais. Desta forma, a utilidade do método rotacional (VOCAL®) para este fim nunca foi testada. Objetivos: Avaliar as variabilidades intra e interobservadores e a concordância entre as medidas do volume da coxa fetal realizadas com os métodos multiplanar e VOCAL®. Comparar as acurácias das fórmulas com medidas do volume da coxa fetal com as acurácias das fórmulas com medidas 2D. Comparar as acurácias das fórmulas deste estudo com as acurácias das fórmulas já publicadas. Métodos: 210 pacientes foram avaliadas, formando um grupo para gerar as fórmulas (n = 150) e um grupo para validá-las (n = 60). Os pacientes utilizados para gerar as fórmulas também foram utilizados para avaliar as variabilidades intra e interobservadores e a concordância entre as medidas realizadas pelos métodos multiplanar e VOCAL®. Foram utilizadas análises de regressão polinomial para criar uma equação com medidas 2D, uma com o volume da coxa fetal medido pelo método multiplanar (CoxaM) e uma com o volume da coxa fetal medido pelo método VOCAL® (CoxaV). Utilizaram-se testes t de Student pareados para comparar as acurácias das equações deste estudo com as acurácias das fórmulas já publicadas. Foram utilizadas análises proporcionais de Bland e Altman para avaliar as variabilidades intra e interobservadores e a concordância entre as medidas realizadas pelos métodos multiplanar e VOCAL®. Resultados: A diferença média percentual entre as medidas pelos métodos multiplanar e VOCAL® foi de -0,04 com limites de concordância de 95% de -8,17 e 8,09. A diferença média percentual e os limites de concordância de 95% entre as medidas na avaliação das variabilidades intra e interobservadores foram -1,10 (-7,67 to 5,47) e 0,61 (-7,68 to 8,91) para o método VOCAL® e 1,03 (-6,35 to 8,41) e -0,68 (-11,42 to 10,06) para o multiplanar. As melhores fórmulas para cálculo do peso fetal estimado (PFE) foram: PFE = -562.824 + 11.962 x CA x CF + 0,009 x DBP² x CA² (CA: circunferência abdominal; CF: comprimento femoral; DBP: diâmetro biparietal); PFE = 1033.286 + 12.733 x CoxaM; PFE = 1025.383 + 12.775 x CoxaV. Tanto no grupo que gerou as fórmulas como no grupo utilizado para validá-las não houve diferença significativa entre as acurácias das fórmulas com medidas 2D ou tridimensionais (3D). Quando aplicadas nas pacientes deste estudo, as acurácias das fórmulas 2D e 3D já publicadas foram significativamente piores dos que as das novas fórmulas. Conclusões: Os métodos VOCAL® e multiplanar são intercambiáveis para a volumetria da coxa fetal. Possivelmente as maiores fontes de discrepâncias na estimativa do peso fetal são as diferenças fenotípicas entre as pacientes utilizadas para criar as fórmulas. Os dados deste estudo reforçam a necessidade de fórmulas específicas para cada população, independentemente do uso de medidas 2D ou 3D. / Abstract: Introduction: Some authors have demonstrated that the prediction of birth weight using fetal limb volumetry is more precise than with two-dimensional ultrasound (2DUS). To date, only the multiplanar method has been used for fetal limb volumetry, so the usefulness of the rotational technique (VOCALTM - Virtual Organ Computer- aided AnaLysis) for this purpose has never been tested. Objectives: To evaluate the repeatability, reproducibility and agreement of measurements performed with multiplanar and VOCALTM techniques for total fetal thigh volumetry. To compare the accuracies of birth-weight-predicting models with total fetal thigh volumetry with models derived from 2DUS parameters. To compare the performances of our new formulas with those of previously published equations. Methods: 210 patients were prospectively evaluated to compose a formula-generating group (n = 150) and a prospective-validation group (n = 60). The patients of the formula-generating group were also used to evaluate the repeatability, reproducibility and the agreement of the measurements of multiplanar and VOCALTM techiniques for fetal thigh volumetry. Polynomial regression analysis was performed in the formula-generating group to generate one equation with 2DUS measurements, one with fetal thigh volume measured by the multiplanar technique (ThiM) and one with fetal thigh volume obtained by the VOCALTM method (ThiV). Paired samples t-tests were used to compare the accuracies of our equations with those of previously published 2D and three-dimensional (3D) equations. Proportionate Bland and Altman analyses were performed to determine the agreement between the two methods and to evaluate intra- and inter-observer variability. Results: The mean percentage difference between measurements performed with the VOCALTM and multiplanar techniques was -0.04 and the 95% limits of agreement were -8.17 and 8.09. The mean percentage difference and 95% limits of agreement between paired measurements in the assessment of intra- and inter-observer variability were -1.10 (-7.67 to 5.47) and 0.61 (-7.68 to 8.91) for the VOCALTM technique and 1.03 (-6.35 to 8.41) and -0.68 (-11.42 to 10.06) for the multiplanar method. The formulas with the best fit for the prediction of birth weight (EFW) were: EFW = -562.824 + 11.962 x AC x FL + 0.009 x BPD² x AC² (AC: abdominal circumference; FL: femur length; BPD: biparietal diameter); EFW = 1033.286 + 12.733 x ThiM; EFW = 1025.383 + 12.775 x ThiV. For both the formula-generating and the rospective-validation groups, there was no significant difference between the accuracies of the new 2DUS and 3DUS models. When applied to our population, the accuracies of previously published 2DUS and 3DUS formulas were significantly worse than our models. Conclusions: The VOCALTM and multiplanar techniques can be used interchangeably for total fetal thigh volumetry. We believe that the greatest sources of discrepancies in estimation of birth weight are the phenotypic differences among patients used to create each of the formulas mentioned in this study. Our data reinforce the need for customized birth weight prediction formulas, regardless of whether 2DUS or 3DUS measurements are employed. / Mestrado / Tocoginecologia / Mestre em Tocoginecologia

O diabetes melito gestacional (DMG) está relacionado ao crescimento fetal exagerado. Entender a influência de fatores relacionados ao crescimento fetal auxilia na identificação dos fetos com maior risco de desvios da normalidade. Objetivo: comparar fatores clínicos, laboratoriais e a expressão placentária de transportadores de glicose segundo o crescimento fetal em pacientes com DMG. Método: Para análise dos fatores clínicos e laboratoriais foi realizado um estudo retrospectivo com 425 gestantes com DMG do Setor de Endocrinopatias da Divisão de Clínica Obstétrica do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC FM-USP) no período de janeiro de 2003 a novembro de 2009. Para a análise da expressão placentária dos transportadores de glicose dos tipos 1 (GLUT1), 3 (GLUT3) e 4 (GLUT4) foram selecionados todos os casos de recém-nascidos grandes para idade gestacional (RNGIG) pareados com um caso controle de recém-nascido adequado para idade gestacional (RNAIG). Foram incluídas apenas gestações únicas e com DMG diagnosticado pelo teste de tolerância à glicose oral de 100 gramas, sem malformações fetais e com idade gestacional definida e confiável. Todas as gestantes realizaram dieta para diabetes, controle glicêmico diário e uso de insulina quando necessário. Os critérios de seguimento e tratamento seguiram rigorosamente as normas do Protocolo de Condutas do Setor de Endocrinopatias da Divisão de Clínica Obstétrica do HC-FMUSP. As gestantes foram divididas para análise dos dados em dois grupos: Fatores clínicos e laboratoriais com: 376 RNAIG e 49 RNGIG num total de 425 DMG. Expressão Placentária dos Transportadores de Glicose: 50 RNAIG e 44 RNGIG. Foram realizados testes de associação e médias das variáveis e relacionadas com os grupos de RNAIG e RNGIG. Resultados: Na análise univariada, dos fatores clínicos e laboratoriais, não houve diferenças entre os grupos quanto a: idade materna, antecedente familiar de diabetes, antecedente pessoal de hipertensão arterial, número de gestações, valores de glicemia de jejum e 1 hora no TTGO-100g, idade gestacional no parto, sexo do RN, tipo de parto e índice de Apgar no 1º e 5º minutos. Houve diferenças estatisticamente significativas entre os grupos quanto a: índice de massa corpórea pré-gestacional (p < 0,02); uso de insulina (p < 0,041); macrossomia anterior (p < 0,001); idade gestacional do diagnóstico do DMG (p < 0,001); glicemias de duas e três horas no TTGO-100g respectivamente com (p < 0,003) e (p < 0,026). Na análise de regressão logística foram considerados preditores independentes da ocorrência de RNGIG: o índice de massa corpórea pré - gestacional, a macrossomia anterior, aidade gestacional do diagnóstico do DMG e a glicemia de duas horas após sobrecarga de 100 gramas. Em relação a expressão dos transportadores de glicose não diferiram entre os grupos em relação a expressão de GLUT1 na decídua, GLUT3 na decídua e vilosidades e GLUT4 na decídua e vilosidades. Houve diferença entre os grupos quanto à: a expressão do GLUT1 nas vilosidades. Conclusões: O índice de massa corpórea pré - gestacional, a macrossomia anterior, a idade gestacional do diagnóstico do DMG e a glicemia de duas horas após sobrecarga de 100 gramas foram preditores da ocorrência de RNGIG. A expressão de GLUT1 nas vilosidades coriônicas teve relação com a ocorrência de RNGIG / Gestational diabetes mellitus (GDM) is related to excessive fetal growth. Knowing the influence of factors related to fetal growth assists in the identification of fetuses at high risk of deviations from normality. Objective: To compare clinical and laboratory tests and the placental expression of glucose transporters according to fetal growth in patients with GDM. Method: A retrospective study of clinical and laboratory factors related with large for gestational age newborns, included 425 pregnant women with GDM was carried out at Sector Endocrine Clinic of Obstetrics Hospital of the School of Medicine, University of São Paulo (HC-FMUSP), between January 2003 to November 2009. For the analysis of placental expression of glucose transporters types 1 (GLUT1), 3 (GLUT3) and 4 (GLUT4) were selected all cases of newborns large for gestational age (LGA) paired with a case control newly born appropriate for gestational age (AGA). We included only patients with singleton pregnancies and GDM diagnosed by OGTT-100g, with newborns without malformations and birth weight classified as adequate or large for gestational age. All pregnant women received diet for diabetes, daily glycemic control and insulin when necessary. The criteria for monitoring and treatment followed strictly the standards of Conduct Protocol Endocrine Obstetric Clinic of the Clinic Hospital, School of Medicine, University of São Paulo. The pregnancies were divided for analysis into two groups: 376 cases of newborns AGA and 49 cases of newborns LGA. Data were analyzed and considered the probability value p <0.05. Results: In the univariate analysis of clinical and laboratory factors, there were no differences between the groups regarding maternal age, family history of diabetes, personal history of hypertension, number of pregnancies, blood fasting glucose and 1 hour in- OGTT 100g, gestational age at delivery, gender of the newborn, type of delivery, Apgar score at 1st and 5th minutes. There were statistically significant differences between the groups regarding: body mass index before pregnancy (p <0.02), insulin (p <0.041), previous macrosomia (p <0.001), gestational age at diagnosis of GDM (p <0.001), blood glucose levels two and three hours at 100 g OGTT, respectively, with (p <0.003) (p <0.026). In logistic regression analysis were considered independent predictors of the occurrence of LGA: body mass index before pregnancy, previous macrosomia gestational age at diagnosis of GDM and two hours after glucose overload 100 grams. Regarding the expression of glucose transporters, the groups did not differ regarding the expression of GLUT1 in the decidua, GLUT3 in the decidua and villi and GLUT4 in the decidua and villi. There were differences between the groups regarding the expression of GLUT1 in the villi. Conclusions: The body mass index before pregnancy, previous macrosomia, gestational age of diagnosis of GDM and two hours after glucose overload 100 grams were predictors of the occurrence of LGA. The expression of GLUT1 in chorionic villi was related to the occurrence of LGA newborn

O diabetes melito gestacional (DMG) está relacionado ao crescimento fetal exagerado. Entender a influência de fatores relacionados ao crescimento fetal auxilia na identificação dos fetos com maior risco de desvios da normalidade. Objetivo: comparar fatores clínicos, laboratoriais e a expressão placentária de transportadores de glicose segundo o crescimento fetal em pacientes com DMG. Método: Para análise dos fatores clínicos e laboratoriais foi realizado um estudo retrospectivo com 425 gestantes com DMG do Setor de Endocrinopatias da Divisão de Clínica Obstétrica do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC FM-USP) no período de janeiro de 2003 a novembro de 2009. Para a análise da expressão placentária dos transportadores de glicose dos tipos 1 (GLUT1), 3 (GLUT3) e 4 (GLUT4) foram selecionados todos os casos de recém-nascidos grandes para idade gestacional (RNGIG) pareados com um caso controle de recém-nascido adequado para idade gestacional (RNAIG). Foram incluídas apenas gestações únicas e com DMG diagnosticado pelo teste de tolerância à glicose oral de 100 gramas, sem malformações fetais e com idade gestacional definida e confiável. Todas as gestantes realizaram dieta para diabetes, controle glicêmico diário e uso de insulina quando necessário. Os critérios de seguimento e tratamento seguiram rigorosamente as normas do Protocolo de Condutas do Setor de Endocrinopatias da Divisão de Clínica Obstétrica do HC-FMUSP. As gestantes foram divididas para análise dos dados em dois grupos: Fatores clínicos e laboratoriais com: 376 RNAIG e 49 RNGIG num total de 425 DMG. Expressão Placentária dos Transportadores de Glicose: 50 RNAIG e 44 RNGIG. Foram realizados testes de associação e médias das variáveis e relacionadas com os grupos de RNAIG e RNGIG. Resultados: Na análise univariada, dos fatores clínicos e laboratoriais, não houve diferenças entre os grupos quanto a: idade materna, antecedente familiar de diabetes, antecedente pessoal de hipertensão arterial, número de gestações, valores de glicemia de jejum e 1 hora no TTGO-100g, idade gestacional no parto, sexo do RN, tipo de parto e índice de Apgar no 1º e 5º minutos. Houve diferenças estatisticamente significativas entre os grupos quanto a: índice de massa corpórea pré-gestacional (p < 0,02); uso de insulina (p < 0,041); macrossomia anterior (p < 0,001); idade gestacional do diagnóstico do DMG (p < 0,001); glicemias de duas e três horas no TTGO-100g respectivamente com (p < 0,003) e (p < 0,026). Na análise de regressão logística foram considerados preditores independentes da ocorrência de RNGIG: o índice de massa corpórea pré - gestacional, a macrossomia anterior, aidade gestacional do diagnóstico do DMG e a glicemia de duas horas após sobrecarga de 100 gramas. Em relação a expressão dos transportadores de glicose não diferiram entre os grupos em relação a expressão de GLUT1 na decídua, GLUT3 na decídua e vilosidades e GLUT4 na decídua e vilosidades. Houve diferença entre os grupos quanto à: a expressão do GLUT1 nas vilosidades. Conclusões: O índice de massa corpórea pré - gestacional, a macrossomia anterior, a idade gestacional do diagnóstico do DMG e a glicemia de duas horas após sobrecarga de 100 gramas foram preditores da ocorrência de RNGIG. A expressão de GLUT1 nas vilosidades coriônicas teve relação com a ocorrência de RNGIG / Gestational diabetes mellitus (GDM) is related to excessive fetal growth. Knowing the influence of factors related to fetal growth assists in the identification of fetuses at high risk of deviations from normality. Objective: To compare clinical and laboratory tests and the placental expression of glucose transporters according to fetal growth in patients with GDM. Method: A retrospective study of clinical and laboratory factors related with large for gestational age newborns, included 425 pregnant women with GDM was carried out at Sector Endocrine Clinic of Obstetrics Hospital of the School of Medicine, University of São Paulo (HC-FMUSP), between January 2003 to November 2009. For the analysis of placental expression of glucose transporters types 1 (GLUT1), 3 (GLUT3) and 4 (GLUT4) were selected all cases of newborns large for gestational age (LGA) paired with a case control newly born appropriate for gestational age (AGA). We included only patients with singleton pregnancies and GDM diagnosed by OGTT-100g, with newborns without malformations and birth weight classified as adequate or large for gestational age. All pregnant women received diet for diabetes, daily glycemic control and insulin when necessary. The criteria for monitoring and treatment followed strictly the standards of Conduct Protocol Endocrine Obstetric Clinic of the Clinic Hospital, School of Medicine, University of São Paulo. The pregnancies were divided for analysis into two groups: 376 cases of newborns AGA and 49 cases of newborns LGA. Data were analyzed and considered the probability value p <0.05. Results: In the univariate analysis of clinical and laboratory factors, there were no differences between the groups regarding maternal age, family history of diabetes, personal history of hypertension, number of pregnancies, blood fasting glucose and 1 hour in- OGTT 100g, gestational age at delivery, gender of the newborn, type of delivery, Apgar score at 1st and 5th minutes. There were statistically significant differences between the groups regarding: body mass index before pregnancy (p <0.02), insulin (p <0.041), previous macrosomia (p <0.001), gestational age at diagnosis of GDM (p <0.001), blood glucose levels two and three hours at 100 g OGTT, respectively, with (p <0.003) (p <0.026). In logistic regression analysis were considered independent predictors of the occurrence of LGA: body mass index before pregnancy, previous macrosomia gestational age at diagnosis of GDM and two hours after glucose overload 100 grams. Regarding the expression of glucose transporters, the groups did not differ regarding the expression of GLUT1 in the decidua, GLUT3 in the decidua and villi and GLUT4 in the decidua and villi. There were differences between the groups regarding the expression of GLUT1 in the villi. Conclusions: The body mass index before pregnancy, previous macrosomia, gestational age of diagnosis of GDM and two hours after glucose overload 100 grams were predictors of the occurrence of LGA. The expression of GLUT1 in chorionic villi was related to the occurrence of LGA newborn

Objectifs : Évaluer l’incidence de la macrosomie fœtale en fonction des différentes définitions (poids de naissance >4000g, >4500g, ≥90ième percentile de Kramer) en vigueur et comparer la prévalence de la morbidité maternelle et périnatale associée à la macrosomie entre les populations Cris et les populations du Québec. Des courbes postnatales spécifiques aux Cris de l’Est de la Baie-James seront proposées. Devis : Comparaison de deux cohortes prospectives Cris et Québec. La cohorte des populations Cris de l’Est de la Baie-James, comporte 2546 femmes recrutées de 2000-2010, au cours de l’étude sur la macrosomie fœtale chez les Cris de l’Est de la Baie James. La cohorte du Québec est composée de 97475 femmes et provient de l’essai clinique randomisé multicentrique QUARISMA, 2008-2010, cette étude promulguant la réduction du taux d’accouchement par  césarienne. Méthodes : Les risques de macrosomie fœtale et de la morbidité maternelle et périnatale sont évalués par des modèles de régression logistique d’équations d'estimation généralisées (EEG) ajustés et comparés selon l’ethnicité, Cris et Québec. GEE. Le groupe de référence étant les femmes du Québec. Les courbes de croissance spécifiques aux Cris sont construites par régression quantile. Résultats : Plus du tiers, soit 36,76%, des Cris et 9,329% des nouveau-nés du Québec, ont un poids de naissance >4000g. Les résultats attestent montrent que 10,92% des Cris de l’Est de la Baie-James ont un poids de naissance de plus de 4500g, ce taux est de 1,23% au Québec. La définition de la macrosomie fœtale, par un poids néonatal ≥90ième percentile de Kramer, identifie 40,02% des bébés Cris, pour 8,83% des nourrissons du  Québec, comme macrosomes. Les Cris sont plus à risque de macrosomie fœtale, comparativement à la population générale du Québec, ces associations sont statistiquement significatives : RC=5,22; 95% IC (4,66-6,05,98), pour un poids de naissance >4000g, RC=8,10; 95% IC (6,22-10,77), pour un poids de naissance >4500g et RC=6,22; 95% IC (5,77-6,72), pour un poids de naissance ≥90ième percentile de Kramer. Le risque de la morbidité périnatale majeure, de la macrosomie fœtale, est généralement moins important pour les Cris que pour la population générale du Québec : 0,76; 95% IC 0,62-0,94. La macrosomie fœtale devrait être décrite par un poids de naissance≥95ième percentile de Kramer, pour les Cris, mais préférablement au 90ième percentile des courbes postnatales spécifiques aux Cris de l’Est de la Baie-James. Les poids de naissance diagnostique spécifiques aux Cris de l’Est de la Baie-James, au 90ième percentile de la 40ième semaine d’aménorrhée, sont de 4 417g pour les filles et 4 488g pour les garçons. Conclusions : Les courbes de Kramer diagnostiquent systématiquement plus de macrosomes chez les Cris que dans la population du Québec. Par contre, le risque de morbidité périnatale majeure est inférieur pour ces communautés autochtones, aux différents seuils décrivant la macrosomie fœtale, ce qui suggère l’utilisation de courbes spécifiques aux Cris et permettrait de diminuer les interventions obstétricales non nécessaires chez les gros bébés Cris, donc non-macrosomes. / Objective: Assess the impact of fetal macrosomia based on definitions (birth weight> 4000 g,> 4500g, ≥90ième percentile Kramer) currently used in Quebec and compare the prevalence of maternal and perinatal morbidity associated with macrosomia between the Cree populations of Eastern James Bay and the general population of Quebec. Specific postnatal curves for the Cree will be constructed. Design: Comparison of two prospective cohort Cree and Quebec. Cohort of Cree populations of eastern James Bay, has recruited 2546 women from 2000 to 2010, during the study of fetal macrosomia in the Cree of eastern James Bay. Quebec cohort consisted of 97,475 women and comes from the multicenter randomized clinical trial QUARISMA 2008-2010, this study promulgates the reduction of caesarean delivery rate. Methods: The risk of fetal macrosomia, maternal and perinatal morbidity, by ethnicity, Cree and Quebec, are evaluated by generalized estimating equations models (GEE). GEE models were adjusted to control for potentially confounding factors. The reference group is Quebec women. The specific growth curves of the Cree are built by quantile regression. Results: More than a third, 36.8%, of Cree populations of Eastern James Bay and 9.3% of newborns in Quebec have a birth weight> 4000g. For a birth weight> 4500g, the results show that 10.9% of the Cree, have a birth weight of more than 4500g, the rate is 1.2% in Quebec. The definition of fetal macrosomia by neonatal birth weight≥90th percentile of Kramer identifies 40.02% Cree’s for 8.8% of infants of Quebec as macrosomic. The Cree population are more at risk of fetal macrosomia, compared to the general population of Quebec, these associations were statistically significant: OR = 5.2; 95% CI (4.6 to 6.0) for birth weight> 4000g, OR = 8.1; 95% CI (6.2 to 10.7) for birth weight> 4500g and OR = 6.2; 95% CI (5.7 to 6.7) for birth weight percentile ≥90th Kramer. The risk of major perinatal morbidity associated with fetal macrosomia, is generally less important for the Cree than for the general population of Quebec: 0.76; 95% CI 0.62-0.94. Fetal macrosomia should be described by birth weight ≥95th percentile of Kramer, for the Cree, but preferably at the 90th percentile of the specific postnatal curves of Cree populations of Eastern James Bay. The specific Cree birth weight thresholds for diagnosing fetal macrosomia, at the 90th percentile of the 40th week of gestation, are 4 417g for the girls and 4 488g for the boys. Conclusion: Kramer’s curves diagnose systematically too much macrosomic Cree babies compare to the general population of Quebec. Futhermore, the risk of major maternal and perinatal morbidity is lower for these indigenous communities, at the different definitions of fetal macrosomia, suggesting the use of specific curves for the Cree, to reduce obstetrics interventions not required in large, but non macrosomic, Cree babies.