Orientadores: Maria Yolanda Makuch, Mary Angela Parpinelli / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-14T02:44:34Z (GMT). No. of bitstreams: 1 Fleury_Camila.pdf: 1750197 bytes, checksum: ecab1a83258efefc9d0f99a995c1c71f (MD5) Previous issue date: 2009 / Resumo: Objetivo: Estudar as vivências e o desenvolvimento da preocupação materna primária de mulheres primíparas diagnosticadas com pré-eclâmpsia. Método: Como marco conceitual para compreender a relação mãe-filho utilizou-se o conceito preocupação materna primária desenvolvido por Winnicott. Foi realizado um estudo clínico-qualitativo. A construção da amostra foi feita por amostragem proposital de homogeneidade ampla, seguindo-se o critério de saturação de informação para a definição do número de participantes. Foram conduzidas entrevistas semidirigidas, utilizando-se um roteiro temático. Todas as entrevistas foram gravadas e transcritas na íntegra. Para a saturação dos dados foi utilizado o referencial teórico sobre a preocupação materna primária. Os dados foram analisados por meio da técnica de análise de conteúdo temática. Resultados: Participaram deste estudo 15 mulheres. O diagnóstico de PE foi uma surpresa para as mulheres, pois até então sua gravidez se desenvolvia sem problemas. Todas as mulheres relataram ter dificuldade para compreender o significado da doença e os episódios de internação. As participantes se referiram a vivências de angústia, solidão, tristeza e ansiedade; e algumas a sentimentos de culpa. A maioria das mulheres teve medo de que seu bebê pudesse morrer ou nascer com complicações ocasionadas por sua doença. O momento do parto foi sentido como um evento repentino e inesperado para as mulheres, distanciando-se de suas fantasias e expectativas e aumentando os sentimentos de falta de controle sobre a situação e medo. Todas relataram que não planejam ter mais filhos, devido ao receio de passarem novamente pela mesma situação. Observou-se nos relatos das participantes que o relacionamento com suas próprias mães influenciou o desenvolvimento de seu papel materno. O apoio da família, principalmente do parceiro, durante a gravidez, parto e puerpério, foi percebido como importante e facilitou a dedicação das mulheres às necessidades do bebê. O apoio dado pela equipe médica também foi sentido como importante. Todas as participantes deste estudo mostraram sinais do desenvolvimento da preocupação materna primária. Durante a gestação já referiam uma aproximação afetiva com o filho, que se manteve e se fortaleceu no puerpério. Na fala das mulheres observou-se o prazer em prestar os cuidados ao bebê, com uma facilidade para interpretar e compreender suas necessidades, além de uma abdicação dos interesses pessoais para se dedicar a esse filho. Conclusão: Mulheres primíparas diagnosticadas com PE, com bebês saudáveis e que permaneceram em contato com elas, sentiram o impacto da doença em suas vidas. Contudo, revelaram-se aptas ao desenvolvimento da preocupação materna primária / Abstract: Objective: Study the life experience of primiparous women diagnosed with pre-eclampsia (PE) and the development of primary maternal preoccupation. Methods: a clinical-qualitative study was performed. Women were selected by purposive sampling of broad homogeneity and the number of participants was determined following the criteria of information saturation. Semi-structured interviews were conducted using a thematic guide. All interviews were recorded and verbatim transcribed. For data analysis Winnicott theoretical concepts regarding the primary maternal preoccupation were used. Furthermore, data was analyzed through the thematic contents analysis technique. Results: A total of 15 women participated in the study. The diagnoses of PE was a surprise to participants because their pregnancy had been without problems. All women had difficulties to understand the meaning of the illness in their lives and of the episodes of hospitalization. Women referred to feelings of anguish, loneliness, sadness and anxiety, in some cases feelings of guilt. Most women felt fear that their baby might die or be born with complication because of their illness. All interviewed women referred that they did not plan on having more children due to the fear of going through the process again. Childbirth was felt as a sudden and unexpected event, different from their expectations and increased their feelings of lack of control and fear. The relationship of the participants with their mothers was related to the development of mother-child relationship. Family support, mainly of their partner during pregnancy, delivery and postpartum, was perceived as important and facilitated their dedication to babies necessities. The support given by health professionals was also perceived as important. All participants had developed signs of primary maternal preoccupation. During pregnancy emotional closeness was observed and this persisted and increased after the baby was born. These women had pleasure in taking care of their babies, were able to recognize and understand their babies' needs and abdicated their own needs and interests to be devoted to their babies. Conclusion: The results of this study show that primiparous woman with diagnosis of PE, whose babies were born healthy and remained with them during postpartum hospitalization, even though they felt the impact of their illness were able to develop a primary maternal preoccupation / Universidade Estadual de Campi / Ciencias Medicas / Mestre em Tocoginecologia

Lipidomics, a rapidly developing field of study, focuses on the classification and quantitation of lipid species. Lipidomics has emerged in the forefront of scientific research due to the key roles that lipids play in metabolism, cancer, and disease. Using mass spectrometry as a tool for analysis, understanding the role eicosanoids and sphingolipids play has advanced rapidly. Being able to observe these small molecules in vivo has led to better understanding of several lipid-driven mechanisms and identification of eicosanoid and sphingolipid biomarkers in neurodegenerative disease, cancer, sepsis, wound healing, and pre-eclampsia. In the studies herein, we developed targeted mass spectrometric methods to identify lipids of interest in inflammatory disease signaling. We further used lipidomics to identify biomarkers in a clinical trial involving patients diagnosed with pre-eclampsia, discovering that ceramide-1-phosphate, a lipid involved in the initiation of inflammation, was significantly decreased in the plasma of patients who developed pre-eclampsia. Additionally, lipidomic studies were used to elucidate the mechanism of the cPLA2α/C1P interaction, in which the binding of C1P to of cPLA2α was ablated (cPLA2α KI) resulting in resistance to sepsis and increased wound closure rate of cPLA2α KI mice. These studies show how useful lipidomics coupled with mass spectrometry can be in studying inflammatory diseases regulated by lipid signaling.

Introduction & Background: Pre-eclampsia is a serious complication of pregnancy that is characterized by high blood pressure, swelling, and proteinuria as the primary symptoms. Preeclampsia affects 5-8 percent of pregnancies in the U. S. Medications can help to manage symptoms; however, delivery is the only way to resolve pre-eclampsia. Preterm delivery is sometimes necessary and is dependent on the gestational age of the fetus and the severity of symptoms in the mother. Women who have hypertension, diabetes, kidney disease or are pregnant with multiples are at higher-risk to develop pre-eclampsia. Purpose Statement Question: The purpose of this research was to identify what complications occur in women after a pre-eclampsia diagnosis. A systematic review of the literature was used to identify relevant articles that address complications of pre-eclampsia. Literature Review: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) were used to guide this systematic review. PubMed, CINAHL, and Google Scholar were used to identify relevant articles. Articles were published with the last 5 years (2018-2023). Search terms were “complications following pre-eclampsia.” A total of 128 results were found and reviewed. Nineteen articles were determined to be eligible for inclusion. Findings: A pre-eclampsia diagnosis comes with considerable risks for women. Short-term risks include elevated blood pressure, preterm delivery, renal dysfunction, and electrolyte imbalance. Longer term complications include chronic hypertension, cardiovascular disorders, stroke, and later memory problems including Alzheimer’s disease. Conclusions: A pre-eclampsia diagnosis confers significant risk to women. Complications can be severe and may affect women and infants long-term.

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 6 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2002. / Härtill 5 uppsatser.

Background: Pre-eclampsia (PET) is one of the major causes of maternal and neonatal morbidity and mortality1. Misclassification of PET can lead to biased or erroneous results in epidemiologic studies resulting in false conclusions. Objectives: The objectives of this thesis are to determine the validity of PET diagnosis in pregnant women in administrative database using the ICD-10-CA codes, to explore the nature of misclassification, and to estimate whether misclassification of PET diagnosis in administrative database may result in biased conclusions. Methods: Pregnant women who participated in the Ottawa and Kingston (OaK) Birth Cohort study and delivered in the Ottawa Hospital were included in the study. All cases with hypertensive disorder of pregnancy in the study population were adjudicated to confirm diagnosis of PET. This adjudicated dataset was used as a reference standard. The PET incidence in hospital discharge database was compared with PET incidence calculated from the reference standard database. Results: 2887 of the requested charts were available for review. The PET incidence was much lower in administrative database (1.47%) than in the OaK Birth Cohort Study (3.6%). The results of the study demonstrated that hospital discharge database via ICD-10-CA was not very sensitive to determine incidence of PET since sensitivity of ICD-10-CA diagnostic codes for PET was low (35.92% with 95% Confidence Intervals (CI): 26.7; 45.9) but specificity, PPV, and NPV were high. The majority of misclassified cases belonged to the category (according to the proposed classification) “PET pregnancies coded with incorrect ICD-10-CA code” (78.88%) followed by the category “Pregnancies affected by PET coded as normal” (14.08%). Conclusion: Using hospital discharge database and ICD-10-CA coding to determine incidence of PET in certain settings may yield low sensitivity. Researchers should validate the results when using the hospital discharge database for PET research to ensure that the findings based on analyses of such data demonstrate what they claimed to demonstrate.

Introdução: A CALPAIN5faz parte da família das cisteínas proteases e está relacionada com a regulação de inúmeras funções celulares, entre elas a diferenciação e a apoptose. Estudos com microarrays identificaram a CALPAIN5como um alvo da açãotranscripcional do HOXA10em úteros de camundongos. Objetivos: No presente estudo avaliou-se a regulação da CALPAIN5pelo HOXA10 em células endometriais, a expressão da CALPAIN5no endométrio durante todo o ciclo menstrual, e na decídua do primeiro e terceiro trimestres de gestações normais, e o padrão de expressão anormal desse gene na pré-eclampsia e endometriose. Material e Métodos: Foram obtidas dez biópsias endometriais (cinco na fase proliferativa e cinco na fase secretora) depacientes férteis. Biópsias de lesões de endometriose, confirmadas por histopatologia,foram retiradas de dez mulheres durante procedimento vídeo-laparoscópico. Amostras de decídua foram coletadas em três diferentes ocasiões: três amostras do primeiro trimestre,cinco amostras no terceiro trimestre e cinco amostras de pacientes com pré-clâmpsia no terceiro trimestre. Identificou-se a proteína da CALPAIN5utilizando imunohistoquimica (IHC) no endométrio eutópico, ectópico e na decídua. Os resultados da IHC foram quantificados, a partir dedois diferentes observadores, utilizando-se Hscorepara células estromais, epiteliais e deciduais. Transfeccionou-se 4,0µg de pcDNA/HOXA10e 20µM siRNA/HOXA10em cultura de células estromais endometriais humanas (HESC) e células epiteliais endometriais humanas (Ishikawa), assim como os seus respectivos controles. A transfecção foi realizada em quadruplicata quando a cultura de células apresentava confluência de 60-70%. Após 48 horas do procedimento o RNA foi extraído, que deu origem a DNA complementar e após uma reação de cadeia da polimerase em tempo real (PCR em tempo real) foi realizada, em triplicata, para determinar o padrão de expressão do HOXA10e CALPAIN5. A análise estatística foi realizada utilizando-se os testes ANOVA com test pos-hocpara o Hscoree teste tpara os resultados da PCR em tempo real. Resultados: CALPAIN5 é expressadurante todo o ciclo menstrual tanto nas células estromais como epiteliais glandulares, e está mais expressa na decídua do primeiro trimestre. Na endometriose CALPAIN5 se mostrou pouco evidente em ambas as células endometriais (estromais e glandulares), quando comparadas de forma geral com as células endometriais eutópicas das pacientes controles, sendo que sua expressão reduziu em 50% (p<0,05). Nas decíduas de pacientes com pré-eclampsia CALPAIN5 apresentou-se mais expressa que no grupo controle (p<0,05). Nas célulasestromais endometriais o pcDNA/HOXA10aumentou a expressão da CALPAIN5em 11 vezes (p<0,05) e a transfecção com siRNA/HOXA10reduziu a expressão da CALPAIN5em 23 vezes (p<0,05). Conclusão: O HOXA10regula a expressão genética da CALPAIN5nas células endometriais. CALPAIN5 é expressa no endométrio normal e tem sua expressão aumentada nas células deciduais do primeiro trimestre em relação àsfases do ciclo menstrual. CALPAIN5 está pouco expressa no endométrio ectópico na endometriose e mais expressa nas células deciduais na pré-eclampsia grave quando comparados com seus respectivos controles. / BACKGROUND: CALPAIN5is member of the calpain-like cystein protease family and has been implicated in the regulation of a variety of cellular functions, including differentiation and apoptosis. Research with microarray screen identified CALPAIN5as target of HOXA10 transcriptional control in murine endometrium. OBJECTIVES: We propose in this study to demonstrate regulated CALPAIN5expression in endometrium, and 3rd trimester deciduas and an abnormal expression pattern of this gene in pre eclampsia and endometriosis . MATERIALS & METHODS: Ten endometrial biopsies (5 proliferative phase and 5 secretory phase) were obtained from fertile controls. Histologically confirmed biopsies of endometriosis were obtained from 10 women atthe time of laparoscopy. Five third trimester decidual samples and 3 first trimester deciduas samples from controls, and five 3rd trimester decidual samples from women with pre-eclampsia were obtained at the time of labor. Immunohistochemistry (IHC) was used to identify CALPAIN5protein in eutopic and ectopic endometrium as well as in decidua. IHC was performed with CALPAIN5polyclonal antibody. IHC results were assessed by 2 evaluators blinded to the study groups, and H-SCORES were determined for the stroma, glands and decidua. The human endometrial stromal cell line, HESC, the human endometrial epithelial cell line, Ishikawa were transfected with either 4.0µg pcDNA/HOXA10or 20µM HOXA10siRNA; transfection with empty pcDNA vector or nonspecific siRNA served as respective controls. Cells were transfected in quadruplicate at 60-70% confluence. Forty eight hours after the transfection total RNA was isolated. qRT-PCR was performed in duplicated to determine expression levels of HOXA10and CALPAIN5in each group. Statistical analysis was performed with ANOVA test pos-hocto Hscoreand ttest for real time PCRRESULTS: CALPAIN5was expressed in endometrial stromal and glandular cells throughout the menstrual cycle, and increased expression was noted in the first trimester decidua phase. There was a decrease in CALPAIN5expression in both stromal and glandular cells in endometriosis to 50% ofthat seen in fertile controls (p<0.05). CALPAIN 5 was also expressed in 3rd trimester decidua obtained from pre-eclamptics at higher levels than 3rd trimester control decidua (p<0.05). The regulatory relationship between HOXA10 and CALPAIN5was established by transient transfection analysis. CALPAIN5 gene expression increased 11-fold (p<0.05) after pcDNA/HOXA10transfection of the HESC, and decreased 23-fold (p<0.05) after HOXA10siRNA treatment. CONCLUSIONS: CALPAIN5 expression is regulated by HOXA10. CALPAIN5is expressed in normal endometrium and at upregulated in the decidua ofwomen with pre-eclampsia. CALPAIN5 expression is decreased in endometriosis compared to eutopic endometrium.

Estudo realizado na Clínica Obstétrica da Faculdade de Medicina da Universidade de São Paulo, com seiscentos e quarenta e cinco gestantes recrutadas, prospectivamente, para avaliações dopplervelocimétricas das artérias uterinas, por via endovaginal, entre 11 e 13+6 semanas e entre 20 e 24+6 semanas. A partir de um grupo de 344 casos com desfecho normal da gestação, valores de referências para os índices dopplervelocimétricos médios foram estabelecidos, e estes foram significativamente maiores na primeira avaliação do que na segunda. Além disso, os valores se correlacionaram de forma positiva e significativa (IP r= 0,42, IR r= 0,42, AB r= 0,29, p<0,0001). Incisura uterina bilateral foi encontrada em 43,9% dos casos no primeiro exame e 4,4% na segunda etapa. Também foram descritos os valores de sensibilidade, especificidade, valores preditivos, razão de verossimilhança e risco relativo de diferentes parâmetros dopplervelocimétricos para predição da pré-eclâmpsia, diagnosticada em 25 casos. Entre 11 e 13 sem. + 6 dias, as áreas sob as curvas de caracterísiticas operacionais dos três índices dopplervelocimétricos foram de 0,51. A maioria dos achados dopplervelocimétricos, nesta fase da gestação, não identificou gestações com risco significativamente aumentado para pré-eclâmpsia. Já, entre 20 e 24 sem. + 6 dias, as áreas sob as curvas de características operacionais foram maiores (IP= 0,66, IR= 0,65, AB= 0,65) e o grupo com índices dopplervelocimétricos acima do percentil 85 e/ou incisura bilateral apresentou risco significativamente aumentado, para o posterior surgimento de pré-eclâmpsia na gestação. Entretanto, a sensibilidade e o valor preditivo positivo foram baixos, e não encorajam o uso desse método para predição da doença hipertensiva específica da gestação em nossa população. / At São Paulo University Medical School, six hundred and forty five pregnant women were prospectively recruited for a longitudinal study involving transvaginal uterine artery Doppler assessment at 11?13+6 weeks and 20?24+6 weeks. Reference values for mean uterine artery Doppler indices were established from 344 cases with normal pregnancy outcome. Values found in the first examination were significantly higher and positively correlated to values obtained in the second examination (PI r= 0.42, RI r= 0.42, SD r= 0.29, p<0.0001). Bilateral notches were found in 43.9% of the cases examined between 11 and 13 weeks, and 4.4% of the cases in the second assessment. Twenty-five cases subsequently developed pre-eclampsia. Sensitivity, specificity, positive and negative predictive values, likelihood ratios and relative risks were calculated for various uterine artery Doppler findings. Between 11 and 13+6 weeks, the ROC curve area was 0.51 for all three indices. At this stage, most uterine artery Doppler findings were not associated with increased risk of pre-eclampsia. At 20 to 20+6 weeks, ROC curve areas were higher (PI= 0.66, RI= 0.65, SD= 0.65) and increased impedance to flow (above the 85th centile) and/or bilateral notches were associated with a significant increase of the risk for the subsequent development of pre-eclampsia. However low sensitivity and positive predictive values do not support this as a screening method for pre-eclampsia in our population.

This thesis aims to undertake health technology assessments in high risk pregnancies through the following objectives: 1. In women with pre-eclampsia, a) To evaluate the association of maternal genotype and severe pre-eclampsia b) To assess the accuracy of tests in predicting adverse pregnancy outcomes c) To develop composite outcomes for reporting in trials on late onset pre-eclampsia 2. In women with multiple pregnancy, a) To study the association between chorionicity and stillbirth b) To identify the optimal timing of delivery in monochorionic and dichorionic twin pregnancies 3. In the field of prediction research in obstetrics a) To provide an overview of the existing prognostic models and their qualities b) To evaluate the methodological challenges and potential solutions in developing a prognostic model for complications in pre-eclampsia Methods The following research methodologies were used: Delphi survey, systematic reviews and meta-analyses. Results 1. a) Maternal genotype and severe pre-eclampsia: 57 studies evaluated 50 genotypes; increased risk of severe pre-eclampsia with thromobophilic genes. b) Accuracy of tests in predicting pre-eclampsia complications: 37 studies evaluated 13 tests. No single test showed high sensitivity and specificity. c) Delphi survey of 18/20 obstetricians and 18/24 neonatologists identified clinically important maternal and neonatal outcomes and maternal and neonatal composite outcomes were developed. 2. Prospective risk of stillbirth and neonatal deaths in uncomplicated monochorionic and dichorionic twin pregnancies: 32 studies were included. In dichorionic twin pregnancies, the risk of stillbirths was balanced against neonatal death at 37 weeks' gestation. In monochorionic pregnancies, there was a trend towards increase in stillbirths after 36 weeks but this was not significant. 3. a) From 177 studies included, 263 obstetric prediction models were developed for 40 different outcomes, most commonly pre-eclampsia, preterm delivery, mode of delivery and small for gestational age neonates. b) The obstetric prognostic model challenge of dealing with treatment paradox was explored and seven potential solutions proposed by expert consensus. Conclusion I have identified the strength of association for genes associated with complications in pre-eclampsia, components for composite outcomes for reporting in studies on pre-eclampsia, and the optimal timing of delivery for twin pregnancies. My work has highlighted the gaps in prediction research in obstetrics and the limitations of individual tests in pre-eclampsia.

The discovery of fetal-derived circulating nucleic acids in maternal plasma has opened up new opportunities for non-invasive prenatal diagnosis. This non-invasive means of obtaining fetal genetic materials is safer than invasive tissue-sampling procedures, which are associated with a small but finite chance of fetal loss. Over the past decade, the detection of fetal DNA in maternal plasma has evolved from dependency on discriminative genetic markers, such as Y-chromosome-specific loci or paternally-inherited polymorphisms, to detection of circulating RNA, fetal-specific methylation or by massively parallel sequencing. Fetal-specific methylation, or fetal epigenetic marker, does not require prior knowledge of the sex or polymorphic status of the fetus and thus can be applied in essentially all pergnancies. This thesis focuses on the development of this kind of marker for non-invasive monitoring and detection of pre-eclampsia and fetal aneuploidies. / The first part of this thesis describes the use of a reported fetal epigenetic marker, RASISF1A, to measure the fetal DNA concentrations in maternal plasma of pre-eclamptic subjects versus gestational-age-matched controls. The second part of this thesis describes a systematic search for potential epigenetic markers for pre-eclampsia and the second commonest fetal aneuploidy, trisomy 18. Numerous approaches for methylation profiling are described, such as methylation-specific polymerase chain reaction (MSP), bisulfite sequencing, a mass spectrometry-based platform (the Epityper assay), and methylated DNA immunoprecipitation coupled with tiling array analysis (MeDIP-chip). Using MeDIP-chip, I selected the most promising fetal epigenetic markers on chromosome 18, and further characterised their detection in maternal plasma. The final part of this thesis describes an approach called epigenetic-genetic (EGG) chromosome dosage for the detection of trisomy 18 based on those markers. I have demonstrated that it is feasible to detect fetal trisomy 18 by analysing maternal plasma in as early as the first trimester. / This thesis illustrates different strategies for methylation profiling and presented two examples of applying DNA methylation for the non-invasive prenatal assessment of pregnancy-associated disorders and fetal chromosomal aneuploidies. I envision that a similar strategy could be developed for other pregnancy-related diseases to broaden the application of epigenetic markers in non-invasive prenatal diagnosis. / Tsui, Wai Yi. / Adviser: Y.M. Dennis Lo. / Source: Dissertation Abstracts International, Volume: 73-02, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 198-221). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.