Orientador: Iracema de Mattos paranhos Calderon / Coorientador: Adriano Dias / Banca: Marilza Vieira Cunha Rudge / Banca: Roberto Antonio Araujo Costa / Banca: Evandro Antonio Bertoluci / Banca: Rossana Pulcineli Vieira Francisco / Resumo: Construir uma curva de altura (AU) uterina em função da idade gestacional em gestantes portadoras de diabete melito tipo 2 (DM2), diabete melito gestacional(DMG) e hiperglicemia gestacional leve (HGL) e compará-la com outras curvas da literatura. Método: Estudo observacional e prospectivo, incluindo 422 gestantes portadoras de diabete e hiperglicemia, atendidas no Serviço Especializado de Diabete e Gravidez da FMB/Unesp, no período de outubro de 2003 a outubro de 2008. Um único examinador obteve 2470 medidas de AU, entre 13 e 41 semanas, com média de 5,85 medidas/gestante e variação de 27 a 209 medidas de AU/semana de gestação. O controle glicêmico foi avaliado por 2074 dosagens de glicemia e, as respectivas médias glicêmicas (MG), avaliadas pelo perfil glicêmico correspondente às semanas gestacionais das medidas de AU. A MG foi adequada (MG < 120mg/dL) em 94,9% e inadequada (MG ≥ 120mg/dL) em 5,1% das semanas gestacionais. A equação de predição da curva de AU foi expressa por AU = 1,082 + 0,966*semana, com r2 = 84,6%. A sobreposição gráfica das curvas evidenciou limites de P10 e P90 mais elevados na curva deste estudo que os observados nas curvas usadas como referência. A análise estatística confirmou que, neste estudo, os valores das medianas de AU foram significativamente mais elevados que os observados na curva de Freire et al. [13], especialmente após a 19ª semana de gestação. Os resultados deste estudo permitem a proposição dessa nova curva no acompanhamento das gestações complicadas por DM2, DMG e HGL. Entretanto, há necessidade de validação dessa curva, antes da sua implementação na rotina do Serviço / Abstract: to build a fundal height (FH) curve according to gestational age for pregnant women with type 2 diabetes(DM2), gestational diabetes mellitus (GDM) or mild gestational hyperglycemia (MGH), and compare it with three other curves in use in Brazil. Prospective observational study of 422 pregnant women with diabetes and hyperglycemia attending the Pregnancy and Diabetes Center of Botucatu Medical School, São Paulo State University/UNESP between October 2003 and October 2008. Between 13 and 41 weeks of pregnancy, 2470 FH measurements were obtained (mean 5.85 per woman). For the assessment of glycemic control, 2074 glucose level measurements were taken and the glycemic mean (GM) at each gestational week was estimated. Results: GM was adequate (< 120mg/dL) in 94.9% and inadequate (≥ 120mg/dL) in 5.1% of the cases. The equation applied for FH prediction was expressed as FH = 1.082 + 0.966*week (r2 = 84.6%). At visual analysis, P10 and P90 FH measurements were higher in the study curve than in the three other curves. Statistical analysis confirmed that FH median values in this study were higher than those in the curve of Freire et al. [13], especially after 19 weeks of pregnancy. Our results suggest that the curve created in this study can be useful for monitoring pregnancies complicated by DM2, GDM and MGH. Nonetheless, before being introduced into practice routine, this new curve requires validation / Doutor

Orientador: Márcia Guimarães da Silva / Banca: Rosane Ribeiro Figueiredo Alves / Banca: Luciane Alarcão Dias Melício / Resumo: Eventos inflamatórios na interface mateno-fetal estão pronunciados em gestações complicadas por prematuridade e a corioamnionite é reconhecida como a principal causa de morbimortalidade perinatal. As membranas corioamnióticas desempenham papel fundamental na imunidade inata local e inibem o crescimento de micro-organismos, em parte, pela expressão de β defensinas humanas (HBDs). Essas moléculas são antimicrobianos naturais que apresentam atividade antibatcteriana, antifúngica e antiviral e são produzidas por células epiteliais. Quantificar a expressão gênica e avaliar a imunolocalização de HBD-1, HBD-2 e HBD-3 em membranas corioamnióticas de gestações complicadas por prematuridade. Trata-se de um estudo prospectivo e transversal. Fragmentos das membranas corioamnióticas foram coletadas de gestantes atendidas no Serviço de Obstetrícia do Hospital das Clínicas da Faculdade de Medicina de Botucatu, UNESP, Botucatu, São Paulo, Brasil. O grupo estudo foi constituído por 25 membranas corioamnióticas de gestantes em Trabalho de Parto Prematuro na presença ou não de Rotura Prematura de Membranas Pré-Termo que tiveram parto prematuro como desfecho gestacional. Como grupo controle, 27 membranas corioamnióticas de gestações de termo em trabalho de parto foram analisadas. Fragmentos das membranas corioamnióticas foram fixadas em formalina a 10%, embebidas em parafina e seccionadas para análise da imunolocalização de HBD-1, HBD-2 e HBD-3 pela técnica de imunoistoquímica. Outros fragmentos das membranas corioamnióticas foram congelados em nitrogênio líquido e submetidos à extração do RNA total para posterior quantificação da expressão de RNAm de HBD-1, HBD-2 e HBD-3 empregando-se a técnica de PCR em tempo real utilizando o sistema TaqMan Gene Expression Assays (Applied Biosystems). Os resultados obtidos no estudo foram submetidos aos testes z e de Mann Whitney. O software empregado ... / Abstract: Inflammatory events can be pronounced in the maternal-fetal interface in pregnancies complicated by prematurity and chorioamnionitis is a major cause of perinatal morbidity and mortality. The chorioamniotic membranes play fundamental role in the local innate immunity and inhibit the microorganisms growth, partly by the expression of human β defensins (HBDs). These molecules are natural antimicrobials that present antibacterial, antifungal and antiviral activities and are produced by epithelial cells. To quantify the expression and to evaluate the immunolocalization of HBD-1, HBD-2 and HBD-3 in chorioamniotic membranes from pregnancies complicated by prematurity. This was a prospective controlled study. Fragments of chorioamniotic membranes were collected from pregnant women admitted at the Obstetrics Unit of the Clinical Hospital of the Botucatu Medical School, São Paulo State University, Botucatu, São Paulo, Brazil. The study group consisted of 25 chorioamniotic membranes samples from pregnant women with preterm labor, in the presence or not of Preterm Premature Rupture of Membranes (PPROM), who delivery prematurely. In the control group, 27 chorioamniotic membranes from pregnancies at term in the presence at labor were analysed. Samples of the chorioamniotic membranes were fixed in 10% formalin, embedded in paraffin and sectioned for immunolocalization of HBD-1, HBD-2 and HBD-3 by immunohistochemistry technique. Other chorioamniotic membranes samples were collected in liquid nitrogen and total RNA was extracted to quantify mRNA expression of HBD-1, HBD-2 and HBD-3 using real time quantitative PCR employing the TaqMan Gene Expression Assays (Applied Biosystems). Statistical analyses were performed using z and Mann Whitney tests in SigmaStat Software and the level of significance adopted was of 5%. In relation to demographic and obstetrics data no statistically significant difference concerning maternal ... / Mestre

Orientador: Iracema de Mattos Paranhos Calderon / Banca: Roseli Mieko Yamamoto Nomura / Banca: Tamara Beres Lederer Goldberg / Resumo A inadequação do estado nutricional materno influencia o resultado da gestação. Especificamente as gestantes com sobrepeso e obesidade têm risco aumentado para intercorrências clínicas na gestação e consequente resultado adverso perinatal, que podem influenciar na saúde da mãe e do seu filho, não só durante a gestação e no pós-parto, como na vida adulta. OBJETIVO  Avaliar resultados maternos, do parto e dos recém-nascidos de gestações associadas a sobrepeso e obesidade. Avaliar resultados maternos, do parto e dos recém-nascidos de gestações associadas a sobrepeso e obesidade. Estudo prospectivo e descritivo, de uma coorte de 258 gestantes, que iniciaram o pré-natal antes da 20ª. semana. Não foram incluídas ou foram descontinuadas as gestantes classificadas como baixo peso, as gestações múltiplas e aquelas com malformações fetais. De acordo com o IMC pré-gestacional, as gestantes foram alocadas em três grupos: EUTROFIA  IMC pré-gestacional entre 18,5 e 24,9 Kg/m2 (N = 65); SOBREPESO  IMC pré-gestacional entre 25,0 e 29,9 Kg/m2 (N = 66) e OBESIDADE  IMC pré-gestacional ≥ 30,0 Kg/m2 (N = 127). Variáveis maternas, do parto e placenta e dos recém-nascidos foram comparadas entre os grupos. Na análise estatística foram empregados teste do Qui-quadrado, análise de variância (ANOVA), seguida do teste de Tukey e análise de regressão logística, com cálculo de odds ratio e respectivo IC95%. Adotou-se 95% como intervalo de confiança (p < 0,05). As adolescentes ( 19 anos) eram mais eutróficas e as gestantes com idade ≥ 35 anos tinham mais sobrepeso e obesidade (p < 0,001). O DM pré-gestacional apresentou associação significativa com a obesidade (15,74%). O ganho de peso foi menor nas gestantes classificadas como obesas (9,56  7,50 Kg) e maior proporção dessas gestantes (45,6%) apresentou GP < 8 Kg (p < 0,001) e aquelas com sobrepeso e obesidade praticaram mais exercício (p = 0,0100). ... / Abstract: Overweight and obesity are associated with increased risks of pregnancy complications and adverse perinatal outcomes, as well as short- and long-term risks for maternal and child health. To assess delivery, maternal and child outcomes in pregnancies associated with overweight and obesity. This descriptive prospective study included 258 pregnant women who started receiving prenatal care at 20 weeks of gestation. Cases of maternallow weight during pregnancy, multiple gestation, and fetal malformation were excluded. According to prepregnancy body mass index (BMI), study participants were allocated into three groups: EUTROPHY- 18.5 < prepregnancy BMI< 24.9 Kgfm2 (n= 65); OVERWEIGHT - 25.0< prepregnancy BMI < 29.9 Kgfm2 (n = 66); and OBESITY- prepregnancy BMI ~ 30.0 Kgfm2 (n = 127). Statistical analyses were performed using the Chi-square test and analysis of variance (ANOVA) followed by the test of Tukey and logistic regression analysis calculating odds ratio and 95%CI (p < 0.05). Most eutrophic women were adolescents (:-;;;19 years) whereas overweight and obesity were mostly observed in women aged ~ 35 years (p < 0.001). Pregestational DM showed a significant association with obesity (15.74%). Weight gain (WG) was lower among women classified as obese (9.56 ± 7.50 Kg). In largest proportion (45.6%) of women with GP < 8 Kg was found in the obesity group, (p < 0,001). Exercising was more frequent in the overweight and obesity groups (p = 0.0100). A greater proportion of obese mothers (13.39%) had large for gestational age babies (p = 0.0209), and highest mean chest perimeter, abdominal perimeter, placental weight, and placental index. Overweight and obesity increased the risk of gestational hypertension, gestational diabetes mellitus, and mild hyperglycemia. The infants born to obese mothers stayed in hospital for a longer time (3.86 ± 3.93) (p = 0.005). Our results confirm adverse outcomes and underscore the importance of identifying and ... / Mestre

This study examined the role of birth complications, delinquent peers and siblings, and specific dopamine receptors on the development of externalizing behavior in children and adolescents, along with the role of heritability in aggression and delinquency. Specifically, it was hypothesized that increased birth complications, presence of specific dopamine receptor (DRD2 and DRD4) risk alleles, and delinquent peers or siblings would be related to increased externalizing behavior at follow-up. The sample consisted of 65 twin pairs, aged six to 16 (mean age = 9.06 years) who originally participated in the Southern Illinois Twins and Siblings Study (SITSS) at age five. Significant results were found for the stability of aggression from age five to follow-up and heritability of parent-rated aggression and delinquency measures was shown. Presence of delinquent peers or siblings was positively related to aggressive and delinquent behavior. Those with more delinquent peers and with the DRD2 risk allele were rated as more delinquent. In contrast, those without the DRD4 risk allele were also rated as more delinquent. Presence of birth complications was positively related to aggressive and delinquent behavior ratings by parents at follow-up. However, birth complications were negatively related to delinquency on youth-rated measures. Finally, those with fewer complications and more delinquent siblings engaged in more reported delinquent behavior. The present study provided important information concerning the effects of birth complications, delinquent peers and siblings, and specific dopamine receptors on the development of externalizing behavior in children and adolescents, along with the role of heritability in aggression and delinquency.

PURPOSE: The goal of this thesis research project is to evaluate and compare post-operative complications among patients, who underwent short and long segment Anterior Cervical Discectomy/Corpectomy and Fusion (ACDF/ACCF). METHODS: Retrospective cohort study design allowed for evaluation of series of variables (age, sex, diagnosis, general post-operative outcome, and complications) while comparing them between the short and long segment groups. RESULTS: Patients within both cohorts tended to experience similar complications, except pseudarthrosis and adjacent segment disease, which both were more prevalent in the long segment group. Diagnosis or short versus long segment length did not have an effect on the general post-operative outcome. One-level ACDF patients were younger than multilevel ACDF surgery patients. Dysphagia was more likely to occur in older patients, with the risk of dysphagia incidence increased by 7% with each year of patient’s age. CONCLUSIONS: Study indicated that longer segment ACDF/ACCF does not carry higher risk of complications incidence than short segment treatment. Further studies are advised to increase generalizability of these results.

INTRODUCTION: Currently, patients diagnosed with Congenital Heart Disease (CHD) are living longer lifespans, leading to an increased number of these patients presenting for non-cardiac procedures/surgeries. Little research has been recently done analyzing intraoperative complications/risks for CHD patients undergoing non-cardiac surgeries. This study aims to identify common intraoperative events experienced by CHD patients undergoing non-cardiac surgeries using more recent data, while at the same time analyzing to see if there is any difference in frequency of intraoperative events experienced between different types of CHD diagnoses. METHODS: After receiving IRB approval, patients with CHD presenting for non-cardiac procedures/surgeries between the years 2008 and 2012 were pulled from Boston Children’s Hospital’s Electronic Medical records. 1,024 non-cardiac surgical encounters from 362 patients were analyzed to determine average age, average weight, patient gender, average ASA class, frequency of CHD diagnoses, ventricular function, type of non-cardiac procedure, premedication administration, type of induction and type and frequency of intraoperative events experienced. The 1,024 encounters were divided into two groups: those done in patients diagnosed with single ventricle physiology (n=79) and those done in patients diagnosed with non-single ventricle physiology (n=945). Unpaired Mann-Whitney tests were performed to determine if there was a significant difference in overall and specific intraoperative event occurrence between the single ventricle and non-single ventricle groups. RESULTS: Average age and weight at the time of these surgical encounters was 4.86 years and 20.57 Kg. A majority of the surgical encounters were done in males (59.2%). Atrial septal defect was the most common type of CHD, and most of the patients in these surgical encounters received an ASA class of 3. Intraoperative events occurred in 24.4% of the surgical encounters with cardiovascular events being the most common (44.82% of total events). Other events made up 30.49% of events experienced intraoperatively, with respiratory events making up the remaining 24.70%. There was a significant difference in the occurrence of overall events between the single ventricle and non-single ventricle group (P<0.0001). Additionally, there was a significant difference in the occurrence of cardiovascular events (P<0.0001) and Other events (P=0.0001) between the single ventricle and non-single ventricle groups. There was no significant difference in the occurrence of respiratory events between the two groups (P=0.648). DISCUSSION: The most common type of intraoperative event experienced by CHD patients during a non-cardiac surgery was cardiovascular events. Significantly more overall intraoperative events, including cardiovascular and other events, occurred in surgical encounters performed on CHD patients exhibiting single ventricle physiology than those encounters done on CHD patients with a non-single ventricle physiology. Results of this study suggest that it would be likely for CHD patients to have a cardiovascular event occur during non-cardiac surgery and that this may be more likely in patients with a single ventricle physiology. This study was subjected to the limitations of retrospective chart review, as well as missing and infrequent documentation. Future analysis will look to find correlations between the occurrence of intraoperative events, and demographic and procedure variables analyzed in this study. / 2017-06-16T00:00:00Z

Philosophiae Doctor - PhD / Maternal mortality is one of the most important problems related to the reproductive health. This is why the reduction by three quarters of maternal mortality by 2015 has been fixed as target No. 5 of the Millennium Development Goals (MDGs). Achieving this goal requires an annual decline of 5.5% of maternal mortality between 1990 and 2015. Unfortunately, the reduction as estimated in 1997 was less than 1% per year. Africa is the continent most affected by this problem. In 2010, the number of maternal mortality in the world was estimated to 287 000 and Africa was hosting more than 52 % (148 000) of the occurrence in the world In Burkina Faso, maternal mortality ratio decreased from 566 in 1991 to 484 in 1998 and 341 in 2010 according to the DHS data while the census estimate was 307 in 2006 and United Nation agencies provided the number of 300 maternal deaths per 100 000 live births in 2010. Statistics provided by the different sources vary considerably. This situation creates confusion among data users. In addition, researches made on the issue remain very insufficient because of the complexity of the issue, lack of data and poor quality of existing data on maternal mortality. This study has been initiated to fill the gap of knowledge about the determinants and estimates of maternal mortality at national and sub-national levels. Results of this research highlighted explanatory factors of maternal mortality at national and regional level with a focus on factors of regional disparities. Findings also provided estimate by adjusting the census 2006 data from missingness and incoherences, improving the census method and testing different other methods. Finally, projection of maternal mortality level is made from 2006 to 2050.

Introdução O transtorno de déficit de atenção/hiperatividade (TDAH) afeta entre 3 e 10% das crianças em idade escolar, ocasionando prejuízos no funcionamento individual, acadêmico e social na infância e adolescência. Apesar disso, sua etiologia ainda não é totalmente conhecida. A alta herdabilidade do TDAH leva a crer que fatores genéticos exerçam papel fundamental na predisposição para o transtorno. Entretanto, a ocorrência da patologia vai depender ainda da interação de genes com fatores de risco ambientais. Restam muitas questões a serem esclarecidas, uma delas é se há relação entre os fatores de risco ambientais e a expressão fenotípica, resultando nos diferentes subtipos do TDAH. Objetivo O objetivo do presente estudo é investigar a associação entre complicações perinatais (complicações ocorridas nos períodos pré, peri e pós-natal imediato - CPPs) e TDAH do subtipo desatento (TDAH-D). Método Participaram desse estudo, crianças e adolescentes entre 6 e 17 anos, provenientes de doze escolas estaduais e de um ambulatório especializado em TDAH de Porto Alegre. Após a realização de extensa avaliação diagnóstica, foram incluídas 124 crianças e adolescentes com o diagnóstico de TDAH-D e 124 controles sem o transtorno, pareados por idade e sexo. Informações sobre complicações ocorridas durante os períodos pré, peri e pós-natal imediato, assim como sobre potencias confundidores, foram coletadas diretamente com as mães biológicas dos sujeitos. Resultados A análise de regressão logística condicional mostrou que, para as crianças e adolescentes cujas mães apresentaram maior número de complicações perinatais, o risco de TDAH-D foi significativamente mais elevado (p = 0.005; OR= 1.25; IC95%: 1.1 – 1.5). Conclusões Em um estudo de caso-controle, foi possível expandir para o TDAH predominantemente desatento os achados prévios que sugeriam a associação entre fatores perinatais e TDAH sem um subtipo específico. / Introduction Attention-deficit/hyperactivity disorder (ADHD) affects between 3% and 10% of school aged children, leading to impaired individual, academic and social functioning in childhood and adolescence. Despite of that, the etiology of ADHD remains unclear. The high heritability points to a large genetic contribution to the etiology of ADHD. However, the development of the disorder will also depend of an interaction between genetic and environmental risk factors. Many questions remain to be answered, such as the association between the ADHD phenotypic heterogeneity and the environmental risk factors, leading to different subtypes of the disorder. Objective The objective of the present study is to investigate the association between pre-, peri-, and early postnatal complications (PDPC) and ADHD predominantly inattentive type (ADHD-I). Method: Children and adolescents between 6 and 17 years old from 12 public schools, and from an ADHD outpatient program both in Porto Alegre were assessed. After an extensive diagnostic evaluation, 124 ADHD-I cases and 124 non-ADHD controls, matched by sex and age, were included in the study. Informations about prenatal, delivery and early postnatal complications, as well as potential confounders were obtained by direct interview with biological mothers. Results: Conditional logistic regression analysis showed that children and adolescents whose mothers presented more PDPC had a significant higher risk for ADHD-I (p = 0.005; OR= 1.25; CI95%: 1.1 – 1.5). Conclusions: In a case-control study, we expanded to ADHD-I previous findings suggesting the association between perinatal factors and broadly defined ADHD.

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Introdução O transtorno de déficit de atenção/hiperatividade (TDAH) afeta entre 3 e 10% das crianças em idade escolar, ocasionando prejuízos no funcionamento individual, acadêmico e social na infância e adolescência. Apesar disso, sua etiologia ainda não é totalmente conhecida. A alta herdabilidade do TDAH leva a crer que fatores genéticos exerçam papel fundamental na predisposição para o transtorno. Entretanto, a ocorrência da patologia vai depender ainda da interação de genes com fatores de risco ambientais. Restam muitas questões a serem esclarecidas, uma delas é se há relação entre os fatores de risco ambientais e a expressão fenotípica, resultando nos diferentes subtipos do TDAH. Objetivo O objetivo do presente estudo é investigar a associação entre complicações perinatais (complicações ocorridas nos períodos pré, peri e pós-natal imediato - CPPs) e TDAH do subtipo desatento (TDAH-D). Método Participaram desse estudo, crianças e adolescentes entre 6 e 17 anos, provenientes de doze escolas estaduais e de um ambulatório especializado em TDAH de Porto Alegre. Após a realização de extensa avaliação diagnóstica, foram incluídas 124 crianças e adolescentes com o diagnóstico de TDAH-D e 124 controles sem o transtorno, pareados por idade e sexo. Informações sobre complicações ocorridas durante os períodos pré, peri e pós-natal imediato, assim como sobre potencias confundidores, foram coletadas diretamente com as mães biológicas dos sujeitos. Resultados A análise de regressão logística condicional mostrou que, para as crianças e adolescentes cujas mães apresentaram maior número de complicações perinatais, o risco de TDAH-D foi significativamente mais elevado (p = 0.005; OR= 1.25; IC95%: 1.1 – 1.5). Conclusões Em um estudo de caso-controle, foi possível expandir para o TDAH predominantemente desatento os achados prévios que sugeriam a associação entre fatores perinatais e TDAH sem um subtipo específico. / Introduction Attention-deficit/hyperactivity disorder (ADHD) affects between 3% and 10% of school aged children, leading to impaired individual, academic and social functioning in childhood and adolescence. Despite of that, the etiology of ADHD remains unclear. The high heritability points to a large genetic contribution to the etiology of ADHD. However, the development of the disorder will also depend of an interaction between genetic and environmental risk factors. Many questions remain to be answered, such as the association between the ADHD phenotypic heterogeneity and the environmental risk factors, leading to different subtypes of the disorder. Objective The objective of the present study is to investigate the association between pre-, peri-, and early postnatal complications (PDPC) and ADHD predominantly inattentive type (ADHD-I). Method: Children and adolescents between 6 and 17 years old from 12 public schools, and from an ADHD outpatient program both in Porto Alegre were assessed. After an extensive diagnostic evaluation, 124 ADHD-I cases and 124 non-ADHD controls, matched by sex and age, were included in the study. Informations about prenatal, delivery and early postnatal complications, as well as potential confounders were obtained by direct interview with biological mothers. Results: Conditional logistic regression analysis showed that children and adolescents whose mothers presented more PDPC had a significant higher risk for ADHD-I (p = 0.005; OR= 1.25; CI95%: 1.1 – 1.5). Conclusions: In a case-control study, we expanded to ADHD-I previous findings suggesting the association between perinatal factors and broadly defined ADHD.