Prediction of preeclampsia in twin pregnancy

Detalhes bibliográficos
Autor(a) principal: Rodrigues, Carla Ferreira Francisco
Data de Publicação: 2018
Idioma: eng
Título da fonte: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
Texto Completo: http://hdl.handle.net/10362/68969
Resumo: Twin pregnancy is a high-risk condition obstetricians have to deal with frequently in clinical practice and its incidence has risen dramatically over the last decades. Additionally, hypertensive disorders including preeclampsia (PE), are amongst the most common medical complications of pregnancy and a major cause of maternal and perinatal morbidity and mortality. While it is unquestionable that multiple pregnancy has an increased risk of PE, it is still unclear what other risk factors are significant in the development of PE in twins. The exact pathophysiology of PE is uncertain. Traditionally it was thought to be a condition of poor placentation, resulting in generalized vascular endothelial activation and vasospasm, with typical cardiovascular clinical manifestations. Recent published data support the hypothesis that an angiogenic/anti-angiogenic balance plays a causative role in endothelial cell injury. The impact of the maternal cardiac function in the development of PE has become more relevant in the last years. The early detection of pregnancies at high-risk of PE could improve the maternal and neonatal outcome by a more individualized patient surveillance and the timely institution of prophylactic measures. In singleton pregnancies, screening for PE in the first trimester using a combined approach has a high detection rate. In twin pregnancies data related to PE screening is limited and inconsistent. The objective of this thesis is to clarify some of the issues with regard to PE in twin pregnancy. We set out to determine the relative risk for total and preterm-PE in multiple pregnancy when compared with singletons. Additionally, the aim is to assess the effect of maternal characteristics and medical history in the prediction of PE in twin pregnancies. The final goal is to develop a screening model for PE in twins by a combination of maternal factors and biomarkers. The research developed consists of three prospective screening studies for PE, with a population of 2219 twin pregnancies. In the first study, we found that there is a hidden high risk of PE in twin pregnancies. Although, as classically described, the relative risk of total PE is about three times higher in twins, the risk of preterm-PE is nine times higher than in singleton pregnancies. In the second study, we evaluated the effect of maternal and pregnancy characteristics on the risk of PE. Screening for preterm PE using maternal factors has a very high detection rate (99-100%) but at the expense of an extremely high screening positive rate (97-99%). In the third study, we developed a model combining maternal characteristics with biophysical and biochemical markers to screen for PE in twin pregnancies. The performance of the screening model for preterm PE was very good with a detection rate for PE before 32 weeks of 100%, at any cut-off used. Once again the screen positive rate was high: 25%, 65% and 75%, using a cut-off 1:10, 1:50 or 1:75, respectively. We believe that increasing the knowledge about PE in twin gestation may allow an improvement in patient’s surveillance, the implementation of an effective screening method and the development of a preventive strategy.
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spelling Prediction of preeclampsia in twin pregnancyPreeclampsiaTwin PregnancyClinical researchGravidez gemelarDomínio/Área Científica::Ciências MédicasTwin pregnancy is a high-risk condition obstetricians have to deal with frequently in clinical practice and its incidence has risen dramatically over the last decades. Additionally, hypertensive disorders including preeclampsia (PE), are amongst the most common medical complications of pregnancy and a major cause of maternal and perinatal morbidity and mortality. While it is unquestionable that multiple pregnancy has an increased risk of PE, it is still unclear what other risk factors are significant in the development of PE in twins. The exact pathophysiology of PE is uncertain. Traditionally it was thought to be a condition of poor placentation, resulting in generalized vascular endothelial activation and vasospasm, with typical cardiovascular clinical manifestations. Recent published data support the hypothesis that an angiogenic/anti-angiogenic balance plays a causative role in endothelial cell injury. The impact of the maternal cardiac function in the development of PE has become more relevant in the last years. The early detection of pregnancies at high-risk of PE could improve the maternal and neonatal outcome by a more individualized patient surveillance and the timely institution of prophylactic measures. In singleton pregnancies, screening for PE in the first trimester using a combined approach has a high detection rate. In twin pregnancies data related to PE screening is limited and inconsistent. The objective of this thesis is to clarify some of the issues with regard to PE in twin pregnancy. We set out to determine the relative risk for total and preterm-PE in multiple pregnancy when compared with singletons. Additionally, the aim is to assess the effect of maternal characteristics and medical history in the prediction of PE in twin pregnancies. The final goal is to develop a screening model for PE in twins by a combination of maternal factors and biomarkers. The research developed consists of three prospective screening studies for PE, with a population of 2219 twin pregnancies. In the first study, we found that there is a hidden high risk of PE in twin pregnancies. Although, as classically described, the relative risk of total PE is about three times higher in twins, the risk of preterm-PE is nine times higher than in singleton pregnancies. In the second study, we evaluated the effect of maternal and pregnancy characteristics on the risk of PE. Screening for preterm PE using maternal factors has a very high detection rate (99-100%) but at the expense of an extremely high screening positive rate (97-99%). In the third study, we developed a model combining maternal characteristics with biophysical and biochemical markers to screen for PE in twin pregnancies. The performance of the screening model for preterm PE was very good with a detection rate for PE before 32 weeks of 100%, at any cut-off used. Once again the screen positive rate was high: 25%, 65% and 75%, using a cut-off 1:10, 1:50 or 1:75, respectively. We believe that increasing the knowledge about PE in twin gestation may allow an improvement in patient’s surveillance, the implementation of an effective screening method and the development of a preventive strategy.A gravidez gemelar é uma condição de alto risco, com a qual os obstetras têm que lidar frequentemente na prática clínica e cuja incidência tem vindo a aumentar drasticamente nas últimas décadas. Por outro lado, a patologia hipertensiva incluindo a pré-eclâmpsia (PE), é uma das complicações médicas mais comuns na gravidez, sendo uma importante causa de morbilidade e mortalidade materna e perinatal. Embora seja inquestionável que a gravidez múltipla tem um aumento do risco de PE, existem ainda dúvidas sobre quais são os outros factores de risco relevantes para PE na gravidez gemelar. A fisiopatologia exata da PE é desconhecida. Tradicionalmente é considerada uma condição resultante de uma placentação anómala, que causa uma ativação endotelial vascular generalizada e vasoespasmo, com manifestações clínicas cardiovasculares específicas. Estudos mais recentes defendem a hipótese de que um equilíbrio angiogênico/antiangiogênico desempenhe um papel causal na lesão das células endoteliais. O papel da função cardíaca materna no desenvolvimento da PE tornou-se mais pertinente nos últimos anos. A identificação precoce de gestações com elevado risco de PE poderá melhorar o desfecho materno e neonatal, através de uma vigilância mais individualizada e da instituição atempada de medidas profiláticas. Nas gravidezes únicas, a utilização no primeiro trimestre de um método de rastreio combinado para a PE tem uma elevada taxa de detecção. Em gravidezes gemelares, os dados sobre o rastreio da PE são limitados e inconsistentes. O objetivo desta tese é esclarecer alguns das dúvidas acerca da PE na gravidez múltipla. Em primeiro lugar pretendemos determinar o risco relativo para PE total e PE pré-termo em gestações gemelares quando comparadas com gestações únicas. Além disso, queremos avaliar o efeito das características maternas e da história clínica na predição de PE em gémeos. O objetivo final é desenvolver um modelo de rastreio para a PE na gravidez gemelar combinando fatores maternos, marcadores biofísicos e bioquímicos. A investigação desenvolvida consiste em três estudos prospectivos de rastreio para PE, realizados em 2219 gravidezes gemelares. No primeiro estudo, constatou-se a existência de um elevado risco oculto de PE na gravidez gemelar. Embora, tal como classicamente descrito, o risco relativo de PE total seja cerca de três vezes superior nos gémeos, o risco de PE pré-termo é nove vezes maior do que em gestações únicas. No segundo estudo, avaliámos o efeito das características maternas e da história clínica no risco de PE. O rastreio da PE pré-termo, através de fatores maternos, tem uma taxa de detecção muito elevada (99-100%), mas à custa de uma taxa extremamente alta de gravidezes com um rastreio positivo (97-99%). No terceiro estudo, desenvolvemos um modelo de rastreio para a PE nas gestações gemelares que combina as características maternas com marcadores biofísicos e bioquímicos. O desempenho do modelo de rastreio para a PE pré-termo foi notável, com uma taxa de detecção de PE antes de 32 semanas de 100%, em qualquer ponto de corte utilizado. Mais uma vez a percentagem de gravidezes com rastreio positivo foi alta: 25%, 65% e 75%, usando um ponto de corte 1:10, 1:50 ou 1:75, respectivamente. Acreditamos que aprofundar o conhecimento sobre PE na gravidez gemelar pode permitir uma melhoria na vigilância destas gravidezes, a implementação de um método de rastreio eficaz e o desenvolvimento de uma estratégia preventiva.Nicolaides, KyprosSerrano, FátimaRUNRodrigues, Carla Ferreira Francisco2019-05-08T13:49:51Z2019-05-072018-09-282019-05-07T00:00:00Zdoctoral thesisinfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10362/68969TID:101549628enginfo:eu-repo/semantics/openAccessreponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiainstacron:RCAAP2024-05-22T17:39:17Zoai:run.unl.pt:10362/68969Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireinfo@rcaap.ptopendoar:https://opendoar.ac.uk/repository/71602025-05-28T17:10:16.609006Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiafalse
dc.title.none.fl_str_mv Prediction of preeclampsia in twin pregnancy
title Prediction of preeclampsia in twin pregnancy
spellingShingle Prediction of preeclampsia in twin pregnancy
Rodrigues, Carla Ferreira Francisco
Preeclampsia
Twin Pregnancy
Clinical research
Gravidez gemelar
Domínio/Área Científica::Ciências Médicas
title_short Prediction of preeclampsia in twin pregnancy
title_full Prediction of preeclampsia in twin pregnancy
title_fullStr Prediction of preeclampsia in twin pregnancy
title_full_unstemmed Prediction of preeclampsia in twin pregnancy
title_sort Prediction of preeclampsia in twin pregnancy
author Rodrigues, Carla Ferreira Francisco
author_facet Rodrigues, Carla Ferreira Francisco
author_role author
dc.contributor.none.fl_str_mv Nicolaides, Kypros
Serrano, Fátima
RUN
dc.contributor.author.fl_str_mv Rodrigues, Carla Ferreira Francisco
dc.subject.por.fl_str_mv Preeclampsia
Twin Pregnancy
Clinical research
Gravidez gemelar
Domínio/Área Científica::Ciências Médicas
topic Preeclampsia
Twin Pregnancy
Clinical research
Gravidez gemelar
Domínio/Área Científica::Ciências Médicas
description Twin pregnancy is a high-risk condition obstetricians have to deal with frequently in clinical practice and its incidence has risen dramatically over the last decades. Additionally, hypertensive disorders including preeclampsia (PE), are amongst the most common medical complications of pregnancy and a major cause of maternal and perinatal morbidity and mortality. While it is unquestionable that multiple pregnancy has an increased risk of PE, it is still unclear what other risk factors are significant in the development of PE in twins. The exact pathophysiology of PE is uncertain. Traditionally it was thought to be a condition of poor placentation, resulting in generalized vascular endothelial activation and vasospasm, with typical cardiovascular clinical manifestations. Recent published data support the hypothesis that an angiogenic/anti-angiogenic balance plays a causative role in endothelial cell injury. The impact of the maternal cardiac function in the development of PE has become more relevant in the last years. The early detection of pregnancies at high-risk of PE could improve the maternal and neonatal outcome by a more individualized patient surveillance and the timely institution of prophylactic measures. In singleton pregnancies, screening for PE in the first trimester using a combined approach has a high detection rate. In twin pregnancies data related to PE screening is limited and inconsistent. The objective of this thesis is to clarify some of the issues with regard to PE in twin pregnancy. We set out to determine the relative risk for total and preterm-PE in multiple pregnancy when compared with singletons. Additionally, the aim is to assess the effect of maternal characteristics and medical history in the prediction of PE in twin pregnancies. The final goal is to develop a screening model for PE in twins by a combination of maternal factors and biomarkers. The research developed consists of three prospective screening studies for PE, with a population of 2219 twin pregnancies. In the first study, we found that there is a hidden high risk of PE in twin pregnancies. Although, as classically described, the relative risk of total PE is about three times higher in twins, the risk of preterm-PE is nine times higher than in singleton pregnancies. In the second study, we evaluated the effect of maternal and pregnancy characteristics on the risk of PE. Screening for preterm PE using maternal factors has a very high detection rate (99-100%) but at the expense of an extremely high screening positive rate (97-99%). In the third study, we developed a model combining maternal characteristics with biophysical and biochemical markers to screen for PE in twin pregnancies. The performance of the screening model for preterm PE was very good with a detection rate for PE before 32 weeks of 100%, at any cut-off used. Once again the screen positive rate was high: 25%, 65% and 75%, using a cut-off 1:10, 1:50 or 1:75, respectively. We believe that increasing the knowledge about PE in twin gestation may allow an improvement in patient’s surveillance, the implementation of an effective screening method and the development of a preventive strategy.
publishDate 2018
dc.date.none.fl_str_mv 2018-09-28
2019-05-08T13:49:51Z
2019-05-07
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dc.type.driver.fl_str_mv doctoral thesis
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instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
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