Orientadores: João Luiz de Carvalho Pinto e Silva, Melania Maria Ramos de Amorim / Tese (Doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-19T23:46:00Z (GMT). No. of bitstreams: 1 Melo_AdrianaSuelydeOliveira_D.pdf: 1803426 bytes, checksum: 1616cc4f0bf8617dfe2ea6d3efb18a75 (MD5) Previous issue date: 2012 / Resumo: Introdução: o crescimento fetal sempre foi um dos grandes receios em relação à prática de exercício durante a gestação. Discute-se se a redistribuição do fluxo sanguíneo feto-placentário durante o exercício físico, com desvio do fluxo das vísceras para a musculatura, poderia levar a uma hipóxia fetal transitória. Objetivo: estudar o impacto do exercício físico supervisionado sobre o fluxo sanguíneo feto-placentário e o crescimento fetal. Métodos: ensaio controlado e aleatorizado (ECA) comparando três grupos de gestantes: início de caminhada com 13 semanas (grupo A), início de caminhada com 20 semanas (grupo B) e um que não realizou exercício físico supervisionado (grupo-controle - C). Foram incluídas 187 gestantes, sendo 62 alocadas para o grupo A, 65 para o B e 60 para o C. Após as perdas, foram avaliados 54 gestantes no grupo A, 60 no B e 57 no C. As gestantes dos grupos de intervenção (A e B) realizaram caminhadas de intensidade moderada três vezes por semana. O nível de condicionamento físico foi avaliado na 13ª, 20ª e 28ª semanas. A evolução do peso fetal, do fluxo sanguíneo útero-placentário e da pressão arterial materna foi avaliada a cada quatro semanas. Avaliou-se também o peso ao nascer. Uma subamostra envolvendo 88 gestantes saudáveis na 36ª semana foi submetida à caminhada de intensidade moderada e cardiotocografia computadorizada (sistema Sonicaid 8002) em três períodos de 20 minutos: repouso, esteira e recuperação pós-esteira. Inicialmente foi realizada análise bivariada para testar a randomização. Para a análise de alguns desfechos avaliados ao longo da gestação (peso fetal, pressão arterial sistólica e diastólica e IP das artérias uterina, umbilical e cerebral média) usou-se o modelo longitudinal. Para avaliar a associação entre bradicardia e as variáveis numéricas foram utilizados ANOVA (continuas) e Kruskall-Wallis (discretas e contínuas sem distribuição normal). Ao final, determinou-se a frequência de bradicardia (FCF menor que 110bpm) e realizou-se análise de regressão logística múltipla stepwise para identificar os principais fatores associados à sua ocorrência. O estudo foi aprovado pelo Comitê de Ética e Pesquisa em Seres Humanos da Universidade Estadual da Paraíba, sob o número 0323.0.133.000-07. Resultados: são apresentados sob a forma de dois artigos. A média de dias de caminhada foi de 68 no grupo A e de 46 no B, com todas as gestantes cumprindo mais de 85% do programa de exercício físico, com melhora do condicionamento físico na avaliação realizada na 28ª semana, sendo observadas médias do VO2max: 27,3 ± 4,3 (A), 28 ± 3,3 (B) e 25,5 ± 3,8 (C), p=0,03. Não foi observada diferença entre os grupos nas características basais. A média do peso ao nascer foi de 3279 ± 453g no grupo A, 3285 ± 477g no B e 3378 ± 593g no C (p=0,53), sem influência no percentual de pequenos e grandes para a idade gestacional. Não se observou associação entre o exercício físico e as demais variáveis investigadas (pré-eclâmpsia, evolução do peso fetal, dos níveis pressóricos e do PI das artérias uterina, umbilical e cerebral média). A média da FCF diminuiu durante a caminhada (repouso: 137 bpm; esteira: 102 bpm e recuperação: 140 bpm, p<0,001), com 78% dos fetos apresentando bradicardia. A melhora no condicionamento físico foi considerada efeito protetor e o aumento do peso materno, fator de risco para bradicardia. Conclusões: em mulheres previamente sedentárias, saudáveis e com gestação única, um programa de exercício físico supervisionado, de intensidade moderada até o final da gestação não apresentou impacto significante nos desfechos avaliados, com influência apenas no nível de condicionamento físico. Apesar do alto percentual de bradicardia observado durante a caminhada, em fetos saudáveis, com a capacidade de readaptar-se a situações de redução de fluxo sanguíneo, o exercício físico mostrou-se seguro. Este estudo foi registrado na plataforma Clinical Trials com o número NCT00641550 / Abstract: Introduction: Fetal growth has always been one of the major concerns regarding the practice of exercise during pregnancy, with discussions on whether the redistribution of fetoplacental blood flow during physical exercise and the bypass of blood from the viscera to the muscles could lead to transitory fetal hypoxia. Objective: To study the. E effect of supervised physical exercise on fetoplacental blood flow and fetal growth. Methods: A randomized, controlled trial was conducted to compare three groups of pregnant women: walking initiated at 13 weeks of pregnancy (Group A), walking initiated at 20 weeks of pregnancy (Group B) and a control group of women who did no supervised physical exercise (Group C). Overall, 187 pregnant women were included in the study: 62 allocated to Group A, 65 to Group B and 60 to Group C. After losses, analysis was conducted on 54, 60 and 57 women in Groups A, B and C, respectively. The women in the intervention groups (A and B) walked at moderate intensity three times a week. Physical fitness level was evaluated at the 13th, 20th and 28th weeks. Fetal weight, uteroplacental blood flow and maternal blood pressure were evaluated every four weeks. Birthweight was also assessed. A sub-sample of 88 healthy women in the 36th week of pregnancy was submitted to moderate intensity walking and computerized cardiotocography (Sonicaid 8002 system) during three phases: resting, treadmill walking and recovery. Initially, bivariate analysis was conducted to test the randomization process. For the analysis of some outcomes evaluated throughout pregnancy (fetal weight, systolic and diastolic blood pressure and the pulsatility indices of the uterine, umbilical and middle cerebral arteries), the longitudinal model was used. To evaluate the association between bradycardia and the numerical variables, analysis of variance (ANOVA) was used for continuous variables and the Kruskall-Wallis test for discrete variables and those continuous variables for which distribution was not normal. Finally, the frequency of bradycardia (fetal heart rate <110 bpm) was determined and stepwise multiple logistic regression was performed to identify the principal factors associated with its occurrence. The study was approved by the internal review board of the State University of Paraíba under reference number 0323.0.133.000-07. Results: Findings are reported as two papers. The mean number of days on which exercise was performed was 68 in Group A and 46 in Group B, with all the women completing more than 85% of the physical exercise program. An improvement in physical fitness was registered at the 28th week, as shown by mean VO2max values: 27.3 ± 4.3 (Group A), 28 ± 3.3 (Group B) and 25.5 ± 3.8 (Group C), p = 0.03. No difference was found between the groups with respect to their baseline characteristics. Mean birthweight was 3,279 ± 453 grams in Group A, 3,285 ± 477 grams in Group B and 3,378 ± 593 grams in Group C (p = 0.53). There was no effect of exercise on the number of small- or large-for-gestational-age infants. No association was found between physical exercise and the other variables investigated (preeclampsia, and fetal weight, blood pressure and the pulsatility indices of the uterine, umbilical and middle cerebral arteries throughout pregnancy). Mean fetal heart rate decreased during walking (resting: 137 bpm, treadmill walking: 102 bpm and recovery: 140 bpm; p<0.001), with 78% of fetuses presenting bradycardia. Improvement in physical fitness was considered a protective effect, while an increase in maternal weight represented a risk factor for bradycardia. Conclusions: In previously sedentary, healthy pregnant women bearing a single fetus, a program of supervised physical exercise of moderate intensity up to the end of pregnancy appears to exert no significant effect on the outcomes evaluated, influencing only physical fitness level. Despite the high percentage of bradycardia found during walking, exercise provide to be safe for healthy fetuses with the ability to readapt to situations in which blood flow is reduced. This study was registered on the Clinical Trials platform under reference number NCT00641550 / Doutorado / Saúde Materna e Perinatal / Doutor em Ciências da Saúde

M.Tech. (Radiography) / Monitoring the growth and wellbeing of the foetus is a major purpose of antenatal care. The use of diagnostic ultrasound to assess foetal wellbeing has become an important part of prenatal care in both low and high risk pregnancies. Pre-eclampsia and foetal growth restriction (FGR) remains important causes of maternal and perinatal mortality and morbidity. Pre-eclampsia is characterised by an abnormal vascular response to placentation and is a multisystem disorder of unknown cause specific to pregnancy which affects the health of both mother and fetus. Prep-eclampsia complicates between 2 and B % of all pregnancies and is the second most common cause of maternal deaths in the developing world. The aim of this study was to assess the sensitivity of uterine artery spectral Doppler screening in the prediction of pregnancies with a high risk of developing pre-eclampsia or FGR before the clinical onset of the disease. The research objectives were to: 1) Determine the sensitivity of first and second trimester uterine artery spectral Doppler assessment in predicting pre-eclampsia or FGR Identify associations between normal and abnormal uterine artery Doppler waveforms and pregnancy outcomes. 2) Determine the most effective Doppler indices 3) Develop ultrasound management guidelines The data was statistically analyzed to determine the sensitivity of uterine artery Doppler screening. In this study uterine artery Doppler screening performed well. in the risk assessment of the most severe cases of pre-eclampsia and FGR. A larger prospective multicenter trial in South Africa is long overdue and therefore a follow-up study to assess Doppler as a screening tool in a high risk population, as per the guidelines formulated.

Abstract Chlamydiae are obligatory intracellular gram-negative bacteria with a unique growth cycle. They are very successful pathogens and responsible for a wide variety infections in humans and different animal species. In addition, they have a tendency to cause recurrent, persistent or chronic infections with potentially severe sequelae years or decades later. The general purpose of this work was to study the possible serological associations between chronic chlamydial infection, systemic inflammation and reproductive health in a general population. The chlamydial heat shock proteins 60 and 10 (Hs10 and Hsp60) have been suggested to contribute to the pathogenesis of chronic chlamydial infections. Thus, the antibodies to chlamydial Hsp10 and Hsp60 were also investigated in complications of pregnancy. The present study was a longitudinal population-based birth cohort study, and all of the original papers of this dissertation are based on a nested case - control design. Our results confirmed the serological association between C. trachomatis infections and subfertility and the rather high incidence of undiagnosed C. trachomatis infections in the male partners of subfertile couples. We further demonstrated a serological association between previous C. trachomatis infections, immunity to chlamydial Hsps and female subfertility. We also showed that serological markers of chronic chlamydial infection present as early as the first trimester are associated with preterm delivery among nulliparous women. When elevated levels of C. trachomatis IgG and hsCRP were present, the estimated risk for preterm delivery was over 4-fold. According to our study, nulliparous women who subsequently developed preeclampsia leading to preterm delivery, which was used as a marker of more serious illness, had significantly more often serum IgG antibodies to C. pneumoniae during the first trimester of pregnancy compared to the preeclamptic women who delivered at term. In conclusion, chronic C. trachomatis infection was found to associate with subfertility both in men and in women. In addition, a subclinical chronic inflammatory process associated at least partly with chronic C. trachomatis infection and present in the first trimester already may be important in the development of preterm delivery. Chronic C. pneumoniae infection and systemic low-grade inflammation were found to associate with pregnancies that lead to preeclampsia and preterm delivery.

Background: Pregnancy associated cardiovascular pathologies have a significant impact on outcome for mother and child. Bioimpedance cardiography may provide additional outcome-relevant information early in pregnancy and may also be used as a predictive instrument for pregnancy-associated diseases. Methods: We performed a prospective longitudinal cohort trial in an outpatient setting and included 242 pregnant women. Cardiac output and concomitant hemodynamic data were recorded from 11th-13th week of gestation every 5th week as well as at two occasions post partum employing bioimpedance cardiography. Results: Cardiac output increased during pregnancy and peaked early in the third trimester. A higher heart rate and a decreased systemic vascular resistance were accountable for the observed changes. Women who had a pregnancy-associated disease during a previous pregnancy or developed hypertension or preeclampsia had a significantly increased cardiac output early in pregnancy. Furthermore, an effect of cardiac output on birthweight was found in healthy pregnancies and could be confirmed with multiple linear regression analysis. Conclusions: Cardiovascular adaptation during pregnancy is characterized by distinct pattern described herein. These may be altered in women at risk for preeclampsia or reduced birthweigth. The assessment of cardiac parameters by bioimpedance cardiography could be performed at low costs without additional risks.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第21953号 / 医博第4495号 / 新制||医||1037(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 柳田 素子, 教授 斎藤 通紀, 教授 近藤 玄 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Publicación a texto completo no autorizada por el autor / Identifica la presencia de estrés emocional en gestantes con diagnóstico de preeclampsia atendidas en el Instituto Nacional Materno Perinatal durante el período de Junio a Julio del 2014. Estudio de tipo observacional, analítico, prospectivo de corte transversal. Para el estudio se contó con la participación de 94 gestantes con el diagnóstico de preeclampsia que fueron atendidas en el servicio C del Instituto Nacional Materno Perinatal durante el periodo de Junio a Julio del 2014. La información fue procesada en una base de datos de Excel y se analizó con el programa estadístico SPSS v.21. Para variables cualitativas se estimó frecuencias absolutas y relativas, y para variables cuantitativas medidas de tendencia central (media y desviación estándar). Para el análisis inferencia se calculó la prueba Chi cuadrado, con un nivel de confianza de 95%. Del total de pacientes con preeclampsia (94), en el 100% se evidenció la presencia de estrés emocional, de los cuales en el 100% de las pacientes se observó estresores internos y en el 79.8% estresores externos al embarazo. El 100% de las pacientes con preeclampsia presenta estresores relacionados con el propio estado físico, el 86.2% estresores relacionados con el bebé, el 80.9% estresores relacionados con el parto. Al referirse a los estresores externos al embarazo, el 69.1% manifiesta estresores de tipo económico, el 30.9% estresores de tipo laboral, el 55.3% estresores relacionados con la pareja, el 30.9% estresores relacionados con la situación familiar y el 70.2% estresores relacionados con otros problemas de salud. El 100% de las gestantes con preeclampsia leve y severa manifiesta estrés interno relacionados al embarazo, el 77.1% de las gestantes con preeclampsia leve refiere que el estrés proviene de forma externa comparado con el 100% de las gestantes con preeclampsia severa; sin embargo no se observan porcentajes significativamente estadísticos (p=0.07). El 65.1% de las gestantes con preeclampsia leve refiere estrés de tipo económico comparado con el 100% de las gestantes con preeclampsia severa con este tipo de estrés, observándose porcentajes estadísticamente significativos (p=0.018). El 59% de las gestantes con diagnóstico de preeclampsia severa manifestó estrés relacionado con la pareja comparado con el 27.3% de gestantes con diagnóstico de preeclampsia leve que presenta este tipo de estrés, mostrándose que ambos porcentajes son estadísticamente significativos (p=0.046). El estrés emocional se manifestó en el total de gestantes (100%) con diagnóstico de preeclampsia, atendidas en el Instituto Nacional Materno Perinatal, de las cuales el 100% presentó estresores inherentes al embarazo y el 79.8% externos al embarazo. Los estresores externos de tipo económico (p=0.018) y los relacionados con la pareja (p=0.046) se observaron con mayor frecuencia en las gestantes con diagnóstico de preeclampsia severa. / Tesis

OBJETIVO Analizar la asociación existente entre el control prenatal y la preeclampsia. MATERIALES Y MÈTODOS Estudio caso control, con 80 historias de pacientes divididas en 40 casos (con preeclampsia) y 40 controles (sin preeclampsia). Los criterios de inclusión tanto para los casos como para los controles fueron: paciente cuyo parto único fue atendido en el hospital San Bartolomé, con seis controles prenatales como mínimo o más, que cuenten con historia clínica en el servicio de archivos del hospital, que presenten diagnóstico médico de preeclampsia (sólo para los casos) y diagnóstico médico de no haber presentado ninguna complicación en el embarazo, parto y puerperio (sólo para los controles). Se excluyeron tanto para los casos como para los controles a pacientes con historias clínicas inadecuadas (enmendaduras, no registrados, registros inapropiados), la presencia de otras patologías previas no asociadas a la hipertensión y a pacientes que además de preeclampsia presentaron otro trastorno hipertensivo sobreagregado (sólo para los casos). La recolección de datos se realizó a través de un formulario que se elaboró mediante el estudio de las historias clínicas y el carné perinatal. Estuvo dividido en cuatro partes, además se hizo un cuadro para la obtención de indicadores en cada control prenatal de las pacientes en estudio consiguiendo datos como: edad gestacional, altura uterina, presión arterial, peso materno, albuminuria, edema y el lugar dónde se realizó cada control prenatal. Todos los datos se analizaron vía estadística descriptiva e inferencial. RESULTADOS El promedio del número total de controles prenatales fue de 7.8±1.9 para las preeclàmpticas y para las no preeclàmpticas fue de 8.8±1.9, (p<0.05). Los controles prenatales inadecuados en las preeclàmpticas fueron de un 55% y para las no preeclàmpticas fue de un 37,5%. Los controles prenatales adecuados fueron de un 45% para las preeclàmpticas y de un 62,5% para las no preeclàmpticas. La asociación efectuada entre el control prenatal y la preeclampsia demostró que existe dos veces más probabilidad de tener un control prenatal inadecuado, y como consecuencia de ello terminar en preeclampsia, comparado con tener, el control prenatal adecuado y terminar sin preeclampsia. CONCLUSIÒN Existe asociación entre los controles prenatales inadecuados y la preeclampsia. / Tesis

Objective: We proposed that women who develop preeclampsia have a low ratio of 'protective' toxicity preventing activity (TxPA) to 'toxic' very low density lipoproteins (VLDL) late in pregnancy. Having confirmed this hypothesis, we then tested whether this low ratio would manifest itself early in the pregnancy of women who develop preeclampsia. Methods: Serially collected plasma from women who developed preeclampsia and from matched controls was assayed blind for TxPA, triglycerides, cholesterol, high-density lipoproteins, albumin, and nonesterified fatty acids (NEFA). Main Outcome Measures: Plasma concentrations of lipids, NEFA, and proteins which bind NEFA (TxPA and albumin) were measured in normal and preeclamptic women. These parameters were formulated prior to data collection because of the low albumin/triglyceride' ratios and the elevated NEFA levels reported to occur in preeclampsia. Results: In late pregnancy, TxPA was lower (1.82 ± 0.63 vs. 2.30 ± 0.40 g/dL, P = 0.008) and VLDL higher (292 ± 130 vs. 206 ± 60 mg/dL, P = 0.013) in preeclamptics than in controls. Discrimination analysis (TxPA and triglyceride), correctly classified 95% of the preeclamptics and 79% of the controls in late pregnancy. The ratio of TxPA to non-TxPA and triglyceride correctly classified 92% of the preeclamptics and 85% of the controls in early pregnancy. Conclusions: The ratio of TxPA to VLDL accurately distinguishes preeclamptic from normal pregnant women, suggesting that both these factors are involved in the development of preeclampsia.

The mechanisms mediating the hypertension of preeclampsia (PE) are unclear. Endogenous digitalis-like factors (EDLFs) are specific sodium pump (SP) inhibitors implicated in essential and experimental hypertension, but they have not been fully explored in the setting of PE. This study uses a digoxin antibody Fab fragment to address the question of whether such factors are present and increased in PE, to investigate a possible treatment of PE, and to isolate and characterize all EDLFs present in PE. Sera and placenta from women with PE did show a significant increase in SP inhibition in comparison to women with normal pregnancy and Digibind® was found to bind EDLFs and essentially block or reverse SP inhibition. Sera were collected in a Phase II, double-blind, placebo controlled clinical study in which women with severe preeclampsia were dosed with Digibind®, as a therapeutic, and the SP activity measured. Sera and placenta from women with PE was also investigated for their inhibitory effects on the SP. Known candidates for EDLFs were investigated for their SP inhibitory effects, as well as how digitalis antibody immune Fab fragments, Digibind® and DigiFab™, bound them and affected the SP activity. Digibind® is also a sufficient affinity material used to isolate and purify PE EDLFs. Additionally, the placentas of preeclamptic women have high levels of similar EDLFs. These studies provide evidence for the existence of EDLFs that circulate in women with PE, and Digibind® is an effective and novel tool to bind, isolate and purify EDLFs in PE.

OBJECTIVES: We conducted a mixed methods study of delayed access to emergency obstetrical care among preeclamptic and non-preeclamptic women in Port au Prince, Haiti, grounded in the Three Delays model of Thaddeus and Maine. The primary objectives were to identify factors affecting delays in accessing care and clinical consequences of delays. METHODS: 524 surveys were administered to women admitted to the Médecins Sans Frontières (MSF) obstetric emergency hospital. Survey questions addressed demographic, clinical, and behavioral risk factors; first (at home), second (transport) and third (health facility) delays; and clinical outcomes for women and infants. Bivariate statistics were used to assess relationships between preeclampsia status and delay, and between risk factors and delay. Twenty-six survey participants with lengthy delays (> 6 hours) were chosen for interviews, which elicited details about delays women experienced. Data were analyzed using a grounded theory approach. RESULTS: We found long delays to accessing care for preeclamptic women (median 5.0 hours, IQR 10.5, vs. 4.0 hours, IQR 5.0, for non-preeclamptic women, p<0.01), primarily due to delays at home before leaving for the hospital (median 2.6 hours, IQR 10.6). No demographic, clinical, or behavioral factors were related to access to care. Women's health prior to pregnancy was not associated with delays, with the exception of preeclamptic women who had previously seen a doctor, who had significantly longer delays than women who had not previously seen a doctor (22.8 hours versus 11.2 hours, p=0.02). Long delays for both preeclamptic and non-preeclamptic women were not associated with poorer clinical outcomes. Although the MSF hospital is free of charge, financial barriers at other hospitals limited access to emergency obstetric care for many women, who commonly experienced non-evidence-based care, including inappropriate education from antenatal care providers when diagnosed with hypertension or preeclampsia. CONCLUSIONS: Pregnant women with preeclampsia in Port au Prince reported significant delays in accessing emergency obstetric care. Many delays stemmed from poor quality antenatal care services, which fail to screen, treat, or educate women appropriately. Improvements should be made in education and supervision for antenatal care providers, and in accessibility of emergency services at public hospitals in Port au Prince.