Abstract available through the Developmental Psychobiology.

Common, complex disorders are polygenic and multifactorial traits representing interactions between environmental, genetic and epigenetic risk factors. More often than not, contributions of these risk factors have been studied individually and this is especially true for complex reproductive traits where application of genomic technologies has been challenging and slow to progress. This thesis explores the potential of genetic and epigenetic components contributing to a better understanding of the biological pathways underlying disease risk in two specific female complex reproductive traits - polycystic ovary syndrome (PCOS) and preterm premature rupture of membranes (PPROM). The PCOS projects focus on characterization of a gene, DENND1A, whose association to PCOS has been established by Genome Wide Association Studies (GWAS) and is known to contribute to PCOS steroidogenic phenotype. In addition, differential microRNAs expression contributing to DENND1A expression regulation in PCOS theca cells was identified. The studies on PPROM utilize a Whole Exome Sequencing approach to identify rare variants in fetal genes contributing to extracellular matrix composition and synthesis contributing to PPROM risk. The results suggest that fetal contribution to PPROM is polygenic and is driven by a significant genetic burden of potentially damaging rare variants in genes contributing to fetal membrane strength and integrity. Tissue and location specific expression patterns of the Chromosome 21 miRNA cluster (miR-99a, miR-125b, let-7c) in fetal membranes from term pregnancies with spontaneous rupture were investigated. The results suggest that these miRNAs play potential roles in fetal membrane rupture and fetal membrane defects associated with T21.

Die nicht-invasive Analyse der fetalen Herzratenvariabilität mittels abdominaler Elektrokardiographie stellt eine neue Methode zur Beurteilung des fetalen Zustandes dar. Die Herzratenvariabilität gilt hier als ein sensitives Maß der autonomen Regulation. Bereits mit Beginn der zweiten Schwangerschaftshälfte ist es möglich, über das mütterliche Abdomen ein fetales Elektrokardiogramm abzuleiten und einer Herzratenvariabilitätsanalyse zuzuführen. Das Untersuchungskollektiv dieser Arbeit umfasste Frauen mit frühem vorzeitigem Blasensprung als Modell einer pathologischen Alteration des fetalen Zustandes sowie Frauen mit normalen Schwangerschaften zwischen der 20. und 28. Schwangerschaftswoche. Die technische Umsetzung und Analyse der fetalen Herzratenvariabilität erfolgte in Kooperation mit dem Institut für Biomedizinische Technik der TU Dresden. Insgesamt wurden 25 Datensätze der Auswertung zugeführt. Eine Reifung des autonomen Nervensystems des Feten mit ansteigendem Gestationsalter konnte mittels der Herzratenvariabilitätsanalyse gezeigt werden. Zur Risikostratifizierung der Feten bei frühem vorzeitigem Blasensprung konnten bei der Betrachtung der Herzratenvariabilitätsparameter keine signifikanten Unterschiede zum Normalkollektiv erhoben werden. Die Analyse der Parameter erfolgte hierbei unabhängig von den fetalen Verhaltenszuständen. Es konnte gezeigt werden, dass die nicht-invasive Analyse der Herzratenvariabilitätsanalyse methodisch und technisch in der Lage ist, den Fetalzustand und dessen Alterationen zu erfassen.

OBJECTIVE: to study the preditivity of PAMG-1 test for patients with suspected premature rupture of membranes (PROM). METHODS: fifty patients with suspected PROM were selected and allocated them into two groups (25 with PROM and 25 without PROM). All patients were subjected to the PAMG-1 test. The preditivity of PAMG-1 test was evaluated for the time between the exam and birth and days in hospital after delivery. For statistical analysis we used the t test, Mann-Whitney and chi-square. A level of 5% of significance was accepted (p<0,05). RESULTS: the sensitivity, specificity, positive and negative predictive values for the PAMG-1 test were 92%. The rates of false positive and false negative were 8%. The accuracy of the test was found to be 92%. The time between the exam and birth was 29h for patients with positive test and 287,8h for patients with negative test (p=0,0001) and maternal hospitalization was 29h and 130h, respectively (p=0,001). CONCLUSIONS: the PAMG-1 test has high preditivity in suspected cases of premature rupture of amniotic membranes, with low rates of false positive and false negative test results. Moreover, it can reduce the time of maternal hospital stay or avoid maternal hospitalization and thereby reduce public health expenditures. / OBJETIVO: estudar a preditividade diagnóstica do teste da PAMG-1 para pacientes com suspeita de ruptura prematura das membranas amnióticas (RUPREME). MÉTODOS: foram selecionadas consecutivamente 50 pacientes com suspeita de RUPREME e alocadas em dois grupos (25 com RUPREME confirmada pelo exame clínico e 25 com RUPREME descartada pelo exame clínico). Todas as pacientes foram submetidas ao teste da PAMG-1. Foram avaliadas a preditividade do teste da PAMG-1, tempo entre a realização do exame e nascimento e tempo de internação materna. Para a análise estatística foi utilizado o teste t de Student, Mann-Whitney e qui-quadrado. O nível de significância admitido foi p<0,05. RESULTADOS: a sensibilidade, especificidade, valores preditivos positivo e negativo para o teste da PAMG-1 foram de 92%. As taxas de falsos positivo e negativo foram de 8%. A acurácia do teste foi 92%. O tempo entre a realização do exame e nascimento foi 29h nas pacientes com teste da PAMG-1 positivo e 287,8h nas pacientes com teste negativo (p=0,0001) e o tempo de internação materna foi 29h e 130h, respectivamente (p=0,001). CONCLUSÕES: o teste da PAMG-1 apresenta elevada preditividade diagnóstica nos casos de suspeita de ruptura prematura de membranas, com baixas taxas de falsos positivo e negativo. Além disso, pode reduzir o tempo ou evitar a hospitalização materna e dessa forma, reduzir gastos com saúde pública.

Made available in DSpace on 2016-07-01T13:10:24Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-04-24. Added 1 bitstream(s) on 2016-07-01T13:14:07Z : No. of bitstreams: 1 000866191.pdf: 1592677 bytes, checksum: cbfcdb8a7242a22f947e68ab4cde944d (MD5) / Introdução: O Trabalho de Parto Pré-Termo (TPP) e a Rotura Prematura de Membranas Pré-Termo (RPM-PT) acarretam severas complicações para o binômio materno-fetal. Entre os fatores de risco associados ao TPP e à RPM-PT, a predisposição genética vem ganhando importância. Contudo, a associação entre genes polimórficos, ancestralidade e a patogênese do TPP e da RPM-PT permanece alusiva. Objetivo: Determinar a associação entre marcadores informativos de ancestralidade (AIMs) e polimorfismos de nucleotídeo único (SNPs) dos genes da Interleucina-1 beta (IL1B), IL6, Receptor de IL6 (IL6R), Fator de Necrose Tumoral Alfa (TNFA), Receptor de TNF alpha (TNFR), IL10, Receptor Toll-like 2 (TLR2), TLR4, Metaloproteinase 9 (MMP9), Inibidor de Metaloproteinase 1 (TIMP1) e TIMP2 maternos e fetais e o TPP e a RPM-PT. Pacientes e Métodos: Foram coletados swabs bucais de gestantes com TPP e/ou RPM-PT e DE seus filhos (TPP: 137 mulheres e 88 filhos; RPM-PT: 64 mulheres e 44 filhos) atendidas no Hospital das Clínicas da Faculdade de Medicina de Botucatu, UNESP, entre os anos de 2003 e 2014. O grupo controle foi constituído por 201 mulheres que tiveram gestações resolvidas a termo e seus 201 filhos, pareadas ao grupo caso por idade materna e sexo do recém-nascido. O DNA total foi extraído dos swabs bucais e submetido à identificação de AIMs por análise de fragmentos e genotipagem de SNPs utilizando Taqman® SNP Genotyping Assays (Applied Biosystems) e Reação em Cadeia da Polimerase (PCR). O software Structure v2.3.4 foi utilizado para estimar mistura étnica materna. Teste de desequilíbrio de ligação e proporção da Hardy-Weinberg foram testados com Genepop 3.4 e haplótipos inferidos com Phase. Os dados sociodemográficos e biológicos foram comparados utilizando os testes de χ2, teste exato de Fisher, Regressão Logística, Manova, Mann-Whitney e Odds Ratio. Resultados: Nas amostras maternas, o TPP foi associado a maior... / Introduction: A genetic predisposition to Preterm Labor (PTL) and Preterm Premature Rupture of Membranes (PPROM) has been suggested; however the relevance of polymorphisms and ancestry to susceptibility to PTL and PPROM in different populations remains unclear. Objective: To evaluate the association between Ancestry Informative Markers (AIM) and Single Nucleotide Polymorphisms (SNPs) in Interleukin-1 beta (IL1B), IL6, IL6 Receptor (IL6R), Tumor Necrosis Factor Alpha (TNFA), TNF Receptor (TNFR), IL10, Toll Like Receptor 2 (TLR2), TLR4, Metalloproteinase 9 (MMP9), Tissue Inhibitors of Metalloproteinase 1 (TIMP1) and TIMP2 genes and the susceptibility to PTL and PPROM in Brazilian women. Patients and Methods: Oral swabs were collected from women with PTL and/or PPROM and their babies (PTL: 137 women and 88 babies; PPROM: 64 women and 44 babies) seen at the Botucatu Medical School's Hospital, between 2003 and 2014. Control group included 402 mother-babies pairs of term deliveries, matched to case group by age and newborn gender. After DNA extraction, AIMs were identified by fragment analysis and SNPs by Taqman® SNP Genotyping Assays (Applied Biosystems) and Polymerase Chain Reaction (PCR). The software Structure v2.3.4 was used to estimate ethnic admixture of mothers. Linkage Disequilibrium and Hardy-Weinberg proportions were tested with Genepop 3.4 and haplotypes inferred using Phase. Mann-Whitney, χ2, Fisher's exact test, Logistic Regression models, Odds Ratio and Manova were used in data analysis. Results: Regarding maternal samples, PTL was associated to European ancestry and smoking and African ancestry was protective. Regarding ancestry analysis, self-reported ethnicity only explained 20% and 15% of the global variation in African and European contributions, respectively. Fetal IL10-592 C and IL10-819 C were also associated to PTL. Maternal alleles IL10-1082 G and TLR2 A increased the risk ...

Orientador: Márcia Guimarães da Silva / Coorientador: Steven Witkin / Banca: Leandro Gustavo de Oliveira / Banca: Erick da Cruz Castelli / Banca: Rodrigo Paupério Soares de Camargo / Banca: Gisele Alboreghetti Nair / Resumo: Introdução: O Trabalho de Parto Pré-Termo (TPP) e a Rotura Prematura de Membranas Pré-Termo (RPM-PT) acarretam severas complicações para o binômio materno-fetal. Entre os fatores de risco associados ao TPP e à RPM-PT, a predisposição genética vem ganhando importância. Contudo, a associação entre genes polimórficos, ancestralidade e a patogênese do TPP e da RPM-PT permanece alusiva. Objetivo: Determinar a associação entre marcadores informativos de ancestralidade (AIMs) e polimorfismos de nucleotídeo único (SNPs) dos genes da Interleucina-1 beta (IL1B), IL6, Receptor de IL6 (IL6R), Fator de Necrose Tumoral Alfa (TNFA), Receptor de TNF alpha (TNFR), IL10, Receptor Toll-like 2 (TLR2), TLR4, Metaloproteinase 9 (MMP9), Inibidor de Metaloproteinase 1 (TIMP1) e TIMP2 maternos e fetais e o TPP e a RPM-PT. Pacientes e Métodos: Foram coletados swabs bucais de gestantes com TPP e/ou RPM-PT e DE seus filhos (TPP: 137 mulheres e 88 filhos; RPM-PT: 64 mulheres e 44 filhos) atendidas no Hospital das Clínicas da Faculdade de Medicina de Botucatu, UNESP, entre os anos de 2003 e 2014. O grupo controle foi constituído por 201 mulheres que tiveram gestações resolvidas a termo e seus 201 filhos, pareadas ao grupo caso por idade materna e sexo do recém-nascido. O DNA total foi extraído dos swabs bucais e submetido à identificação de AIMs por análise de fragmentos e genotipagem de SNPs utilizando Taqman® SNP Genotyping Assays (Applied Biosystems) e Reação em Cadeia da Polimerase (PCR). O software Structure v2.3.4 foi utilizado para estimar mistura étnica materna. Teste de desequilíbrio de ligação e proporção da Hardy-Weinberg foram testados com Genepop 3.4 e haplótipos inferidos com Phase. Os dados sociodemográficos e biológicos foram comparados utilizando os testes de χ2, teste exato de Fisher, Regressão Logística, Manova, Mann-Whitney e Odds Ratio. Resultados: Nas amostras maternas, o TPP foi associado a maior... / Abstract: Introduction: A genetic predisposition to Preterm Labor (PTL) and Preterm Premature Rupture of Membranes (PPROM) has been suggested; however the relevance of polymorphisms and ancestry to susceptibility to PTL and PPROM in different populations remains unclear. Objective: To evaluate the association between Ancestry Informative Markers (AIM) and Single Nucleotide Polymorphisms (SNPs) in Interleukin-1 beta (IL1B), IL6, IL6 Receptor (IL6R), Tumor Necrosis Factor Alpha (TNFA), TNF Receptor (TNFR), IL10, Toll Like Receptor 2 (TLR2), TLR4, Metalloproteinase 9 (MMP9), Tissue Inhibitors of Metalloproteinase 1 (TIMP1) and TIMP2 genes and the susceptibility to PTL and PPROM in Brazilian women. Patients and Methods: Oral swabs were collected from women with PTL and/or PPROM and their babies (PTL: 137 women and 88 babies; PPROM: 64 women and 44 babies) seen at the Botucatu Medical School's Hospital, between 2003 and 2014. Control group included 402 mother-babies pairs of term deliveries, matched to case group by age and newborn gender. After DNA extraction, AIMs were identified by fragment analysis and SNPs by Taqman® SNP Genotyping Assays (Applied Biosystems) and Polymerase Chain Reaction (PCR). The software Structure v2.3.4 was used to estimate ethnic admixture of mothers. Linkage Disequilibrium and Hardy-Weinberg proportions were tested with Genepop 3.4 and haplotypes inferred using Phase. Mann-Whitney, χ2, Fisher's exact test, Logistic Regression models, Odds Ratio and Manova were used in data analysis. Results: Regarding maternal samples, PTL was associated to European ancestry and smoking and African ancestry was protective. Regarding ancestry analysis, self-reported ethnicity only explained 20% and 15% of the global variation in African and European contributions, respectively. Fetal IL10-592 C and IL10-819 C were also associated to PTL. Maternal alleles IL10-1082 G and TLR2 A increased the risk ... / Doutor

Orientador: Renato Passini Júnior / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-11-27T11:47:19Z (GMT). No. of bitstreams: 1 Lajos_GiulianeJesus_D.pdf: 13164683 bytes, checksum: 157ab3724e88a3aa83c69cd29bf06c06 (MD5) Previous issue date: 2014 / Resumo: Introdução: A prematuridade é um problema complexo de saúde pública, sendo a principal causa de morbidade e mortalidade neonatais, com tendência a aumento nas últimas décadas. Foi proposto um estudo com a participação de vários hospitais do Brasil, a fim de avaliar diversos aspectos envolvidos com a ocorrência do parto pré-termo. Objetivos: descrever os métodos de implementação do Estudo Multicêntrico de Investigação em Prematuridade no Brasil; avaliar a homogeneidade amostral dos casos incluídos; estimar a prevalência e analisar fatores associados à prematuridade espontânea. Métodos: estudo transversal multicêntrico, com componente caso-controle aninhado, em 20 hospitais de referência em três regiões geográficas do Brasil. Foram selecionadas as instituições participantes, elaborado o formulário de coleta de dados, escolhido o sistema eletrônico para inclusão de casos, desenvolvido um programa para a digitação dos dados, elaborados manuais de orientação e padronização da coleta de informações, seguidos de implantação do estudo e análise dos dados obtidos. Foi realizada vigilância prospectiva para identificação de partos pré-termo e estimada sua prevalência, subdividindo-os pelas condições determinantes: trabalho de parto espontâneo, ruptura prematura de membranas e parto terapêutico. Foram estimadas taxas de prevalência ou médias, coeficientes de correlação intraclasse, efeitos do desenho do estudo e média de tamanho de conglomerado para mais de 250 variáveis. O risco de parto pré-termo espontâneo foi estimado com Odds Ratio para vários preditores e a análise por regressão logística não condicional identificou fatores independentemente associados. Resultados: Foram incluídas 5.296 mulheres, sendo 4.150 com partos prematuros (casos) e 1.146 com partos a termo (controles), e avaliados 5.752 recém-nascidos. A taxa geral de prematuridade foi 12,3%. Os coeficientes de correlação intraclasse foram baixos (<0,1) na maioria das variáveis. Comparando 2.682 partos prematuros espontâneos com 1.146 partos a termo, a análise multivariada identificou como fatores de risco para o parto pré-termo: antecedente de parto prematuro, gravidez múltipla, suspeita de insuficiência cervical, malformação fetal, polidrâmnio, sangramento vaginal, número insuficiente de consultas de pré-natal, aborto anterior e infecção do trato urinário. Conclusões: A implantação do Estudo Multicêntrico de Investigação em Prematuridade no Brasil foi a primeira etapa de uma ampla avaliação da prematuridade no país. Os coeficientes de correlação intraclasse indicaram adequada heterogeneidade da amostra estudada. Seus valores poderão ser usados como referência no cálculo de tamanho amostral de estudos futuros na área. A prevalência de partos pré-termo nos centros terciários do Brasil foi alta. Antecedente de parto prematuro, gravidez múltipla, suspeita de insuficiência cervical, malformação fetal, polidrâmnio, sangramento vaginal, número insuficiente de consultas de pré-natal, aborto anterior e infecção do trato urinário foram considerados fatores de risco para parto prematuro espontâneo. A identificação desses fatores pode auxiliar no planejamento de medidas para reduzir a ocorrência de partos pré-termo / Abstract: Background: Preterm birth is the main cause of neonatal morbidity and mortality, resulting in a high likehood of sequelae in surviving children, with a tendency to increase in last decades. A study intending to collect information from hospitals in Brazil on several aspects of preterm birth was proposed. Objectives: To describe the methods used in elaborating and implementing the Brazilian Multicenter Study on Preterm Birth; to evaluate the homogeneity of the sample included in the network; to assess the prevalence of preterm births in Brazil and to identify factors associated with spontaneous preterm birth. Methods: The project consisted of a multicenter cross-sectional study plus a nested case-control study in 20 reference hospitals of three regions of Brazil. The elegible hospitals were selected, forms for data collection were prepared, an electronic system for the inclusion of cases was selected, a program for entering data was developed and the implantation process and data analysis were performed. A prospective surveillance was implemented to identify preterm births, to estimate its prevalence, subdividing into determinats conditions: spontaneous labor, prelabor rupture of membranes or therapeutic birth. Estimated prevalence rates or means, intracluster correlation coefficients, design effects and mean cluster sizes were presented for more than 250 variables. The risk of spontaneous preterm birth was estimated with Odds Ratio for several predictors and a non-conditional logistic regression analysis was then performed to identify independently associated factors. Results: Overall, 5,296 women were included in the study, being 4,150 preterm births (cases) and 1,146 term births (controls), and the total number of studied newborns was 5,752. Overall rate of preterm birth was 12.3%. Intracluster correlation coefficients were low (<0.1) in most variables, showing intracluster heterogeneity. When comparing 2,682 spontaneous preterm births to a sample of 1,146 term births, the multivariate analyzes identified as risk factors for preterm birth: a previous preterm birth, multiple pregnancy, cervical insufficiency, fetal malformation, polyhydramnios, vaginal bleeding, inadequate number of prenatal care visits, previous abortion, and urinary tract infection. Conclusions: The implementation of the Brazilian Multicenter Study on Preterm Birth was the first step of a comprehensive assessment of prematurity in the country. Intracluster correlation coefficients for the outcome variables indicate adequate sample heterogeneity. Their values can be used to calculate the sample size of further studies in the area. The preterm birth rate in tertiary facilities in Brazil was high and the proportion of therapeutic preterm births was over one third. Previous preterm birth, multiple pregnancy, cervical insufficiency, fetal malformation, polyhydramnios, vaginal bleeding, inadequate number of prenatal care visits, previous abortion, and urinary tract infection were considered risk factors to spontaneous preterm birth. Identification of these factors can be worth for planning effective measures to reduce the occurrence of preterm births / Doutorado / Saúde Materna e Perinatal / Doutora em Ciências da Saúde

Orientador: Renato Passini Junior / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-11-27T10:57:27Z (GMT). No. of bitstreams: 1 Pinto_GiulianeJesusLajos_M.pdf: 245675 bytes, checksum: 71fd93a1854439989a54c4faa89da2dc (MD5) Previous issue date: 2005 / Resumo: Objetivo: estudar a colonização bacteriana endocervical em gestantes com trabalho de parto prematuro e/ou ruptura prematura de membranas (termo e pré-termo). Método: 212 gestantes com trabalho de parto prematuro (TPP) e/ou ruptura prematura de membranas (RPM), internadas no Hospital Estadual Sumaré (Unicamp), foram avaliadas no período de julho de 2002 a janeiro de 2004. Na admissão hospitalar foram coletadas duas amostras do conteúdo endocervical, realizadas bacterioscopia e cultura em meios ágar-sangue ou ágar-chocolate. Foram analisadas associações da colonização endocervical com infecção de trato urinário materno, corioamnionite, uso de antibióticos, dados de parto, sofrimento fetal, prematuridade, infecção e óbito neonatais. Resultados: entre as mulheres estudadas, 74 (35%) tinham TPP e 138 (65%), RPM. A prevalência de colonização endocervical foi de 14,2% (IC=9,5%-18,9%), com resultados similares em TPP e RPM. Na população estudada, o microorganismo mais encontrado foi o estreptococo do grupo B (EGB) (9,4%), sendo também isolados Candida sp (5 casos), Streptococcus sp (2 casos), Streptococcus pneumoniae, Escherichia coli e Enterococcus sp (1 caso de cada). Das bacterioscopias analisadas, os achados mais freqüentes foram baixa prevalência de bacilos de Dodërlein e elevado número de leucócitos. Em mulheres colonizadas houve maior prevalência de infecção de trato urinário (23,8% versus 5,4%; p<0,01), infecção neonatal (25,0% versus 7,3%; p<0,01) e óbito neonatal (dois casos entre as colonizadas; p<0,02), quando comparadas às não-colonizadas. Conclusões: observou-se alta prevalência de colonização endocervical, sem a utilização de meios de cultura seletivos. O EGB foi o principal microorganismo isolado, reforçando a necessidade de triagem deste agente durante a gestação e nas situações de risco estudadas. Um terço das culturas positivas ocorreram por outros agentes. Estudos complementares são necessários para esclarecer a importância destes achados bacteriológicos no canal endocervical e sua associação com complicações gestacionais, sepse e mortalidade neonatais / Abstract: Objective: to study cervical colonization in women with preterm labor and/or premature rupture of membranes. Method: 212 pregnant women with preterm labor and/or premature rupture of membranes (PROM), admitted at Hospital Estadual Sumaré, during the period between July 2002 and January 2004, were studied. Two cervical samples from each woman were collected and bacterioscopy and culture in blood-agar or chocolate-agar plates were performed. Association of cervical microorganisms and urinary infection, chorioamnionitis, antibiotics use, prematurity, neonatal infection and neonatal death were evaluated. Results: the population evaluated consisted of 74 women with preterm labor (35%) and 138 women with PROM (preterm and term). The prevalence of cervical colonization was 14.2% (CI=9.5-18.9%), with similar results in preterm labor or PROM. Group B streptococcus was the most prevalent organism in this population (9.4%). Other organisms isolated were Candida sp, Streptococcus sp, Streptococcus pneumoniae, Escherichia coli and Enterococcus sp. The most common findings of bacterioscopy were a reduced number of lactobacilli and a great number of leukocytes. Endocervical colonization was associated with a higher occurrence of urinary tract infection (23.8% versus 5.4%; p<0.01), early-onset of neonatal infection (25.0% versus 7.3%; p<0.01) and neonatal mortality (2 cases in colonizated women; p<0.02) when compared with a negative culture of endocervical mucus. Conclusions: this study showed high prevalence of endocervical colonization despite of the use of a nonselective culture media. The main microorganism isolated was Group B streptococcus but other organisms were present in one third of studied population. More studies are needed to evaluate the influence of endocervical colonization in obstetrical outcome and in neonatal sepsis and mortality / Mestrado / Tocoginecologia / Mestre em Tocoginecologia

Η ενδοθηλίνη-1 (ET-1) είναι ένα πεπτίδιο αποτελούμενο από 21 αμινοξέα. Είναι ισχυρός αγγειοσυσπαστικός παράγοντας και μιτογόνο των λείων μυϊκών κυττάρων. Στο πλάσμα ασθενών που πάσχουν από σοβαρού βαθμού υπέρταση ή προεκλαμψία έχουν ανιχνευθεί υψηλές συγκεντρώσεις ΕΤ-1. Ο ακριβής ρόλος της ΕΤ-1 σε σχέση με την ανθρώπινη αναπαραγωγή είναι ακόμη σε μεγάλο βαθμό ένα αίνιγμα. Μητρικές και εμβρυικές συγκεντρώσεις στο πλάσμα της ενδοθηλίνης έχουν μελετηθεί πρόσφατα σε σχέση με την εγκυμοσύνη. Αυτοί περιλαμβάνουν ενδομήτρια καθυστέρηση της ανάπτυξης (IUGR) και προεκλαμψία. Οι ακριβείς μηχανισμοί για αυτές τις παθολογικές διαδικασίες και η αύξηση των συγκεντρώσεων πλάσματος της ενδοθηλίνης είναι ακόμη σε μεγάλο βαθμό άγνωστοι, αν και υπάρχουν στοιχεία που να υποδηλώνουν ότι η ενδοθηλίνη συνδέεται με βλάβη του ενδοθηλίου των κυττάρων. Υπάρχουν τώρα κάποιες ενδείξεις ότι οι αμνιακές συγκεντρώσεις της ενδοθηλίνης είναι αυξημένες σε κυήσεις που σχετίζονται με προ-εκλαμψία. Ο σκοπός αυτής της προοπτικής μελέτης ήταν να καταγράψει την συγκέντρωση ενδοθηλίνης στο αμνιακό υγρό σε γυναίκες με φυσιολογικές κυήσεις συγκριτικά με τις γυναίκες που εμφανίζουν προεκλαμψία , IUGR και προώρη ρήξη εμβρυικων υμένων. Εξετάσθηκε το αμνιακό υγρό που προήλθε από αμνιοπαρακέντηση από 125 γυναίκες κατά το δεύτερο τρίμηνο της εγκυμοσύνης . Τα επίπεδα της ενδοθηλίνης μετρήθηκαν με μια ευαίσθητη και ειδική εξεταση ραδιοανοσοπροσδιορισμού. Η συγκέντρωση στο αμνιακό υγρό της ενδοθηλίνης είναι αυξημένη από το δεύτερο τρίμηνο σε γυναίκες που αργότερα αναπτύσσουν PPROM, PROM, IUGR και προεκλαμψία με στατιστικά σημαντική διαφορά. Έχει αποδειχθεί ότι τα επίπεδα ΕΤ1 συσχετίζονται με το βάρος γέννησης των νεογνών, για τη κυήση που περιπλέκονται με IUGR, με το βάρος γέννησης των νεογνών, και με την ηλικία κύησης για την ομάδα PPROM, κια με το βάρος γέννησης των νεογνών σε κυήσεις με προεκλαμψία. Η διερεύνηση επιπέδων ΕΤ-1 στο αμινιακό υγρό δευτέρου τριμήνου μπορεί να είναι ένας εξαιρετικά σημαντικός χώρος έρευνας στο μέλλον, καθώς θα μπορούσε να ρίξει περισσότερο φως για την πρώιμη ανέυρεση των παθοφυσιολογικων διαδικασιών της πλακουντιακής δυσλειτουργίας. / Endothelin-1 (ET-1) is a peptide consisting of 21 amino acids. It is a strong vasoconstrictor and mitogenic factor with significant activity on to the smooth muscle cells. High concentrations of ET-1 have been detected in plasma of patients with severe hypertension or preeclampsia. The exact role of ET-1 in relation to human reproduction is still largely an enigma. Maternal and fetal plasma concentrations of ET-1 have been studied recently in relation to pregnancy. These include intrauterine growth retardation (IUGR) and preeclampsia. The exact mechanisms of these pathological processes and increased plasma concentrations of ET-1 are still largely unknown, although there is evidence to suggest that ET-1 is associated with impaired endothelial cells. There is now some evidence that amniotic ET-1 concentrations are elevated in pregnancies associated with pre-eclampsia. The purpose of this prospective observational study was to record the ET-1 concentration in second trimester amniotic fluid and compare with the levels in women who develop preeclampsia, IUGR and premature rupture of membranes. The amniotic fluid samples were obtained from 125 women by amniocentesis during the second trimester of pregnancy. The levels of ET-1 were measured with a sensitive and specific radioimmunoassay examination (ELISA). The amniotic fluid concentrations of ET-1 are statistically significantly higher from the second trimester in women who later develop PPROM, PROM, IUGR with preeclampsia. This study showed that ET-1 levels correlated with the birth weight of newborns in the pregnancies complicated by IUGR, the birth weight of newborns and the gestational age for the group PPROM, and with the birth weight of newborns in pregnancies with preeclampsia . Investigating the levels of ET-1 in the second trimester amniotic fluid can be an extremely important research area in the future, and could shed more light on the early discovery of the pathophysiological process of placental dysfunction.

Objective: to evaluate the risk of obstetric and perinatal outcomes in teenage pregnancy in comparison with adult pregnancy. Methods: retrospective cohort study of 67.693 pregnant women attended in a public hospital in Lima between 2000 and 2010. Obstetric and perinatal outcomes were evaluated. The adolescent group was divided in late adolescents (15-20 years), and early adolescents (<15 years) and was compared among the adult group (20-35 years). Adjusted odds ratios were calculated by education, civil status, prenatal care, previous pregnancies, parity, and pre-gesta-tional BMI. Results: higher risk of cesarean (OR=1,28; CI95%=1,07-1,53) and puerperal infection (OR=1,72; CI95%=1,17-2,53) was found in teenager under 15 years old; as well as higher risk of episiotomy (OR=1,34; CI95%=1,29-1,40) in late teenagers. In addition, this study identified a lower risk of teenage pregnancy for preeclampsia (OR=0,90; CI95%=0,85-0,97), 2nd half-pregnancy bleeding (OR=0,80; CI95%=0,71-0,92), premature rupture of membranes(OR=0,83; CI95%=0,79-0,87), preterm labor (OR=0,87; CI95%=0,80-0,94) and vaginal tearing (OR=0,86; CI95%=0,79-0,93). Conclusion: pregnancy behaves as a risk factor for some obstetric outcomes in the adolescent group, especially in the youngest ones. In addition to maternal age, there are other factors that constitute the need to form multidisciplinary teams to reduce obstetric outcomes in this population. / diego.maticorena@gmail.com / Objetivos: analizar el riesgo de complicaciones obstétricas y perinatales en adolescentes embarazadas en un hospital de Lima, Perú. Métodos: estudio de cohorte retrospectiva de 67.693 gestantes atendidas en el período 2000-2010. Se evaluó complicaciones obstétricas y perinatales. Las adolescentes se clasificaron en tardías (15-19 años) y tempranas (< 15 años) y se compararon con las adultas (20-35 años). Se calculó OR ajustados por educación, estado civil, control prenatal, gestaciones previas, paridad e IMC pregestacional. Resultados: se encontró mayor riesgo de cesárea (OR=1,28; IC95%=1,07-1,53) e infección puerperal (OR=1,72; IC95%=1,17-2,53) en las adolescentes menores de 15 años, así como mayor riesgo (OR=1,34; IC95%=1,29-1,40)de episiotomía en las adolescentes tardías. Asimismo, se identificó un menor riesgo del embarazo adolescente para preeclampsia (OR=0,90; IC95%=0,85-0,97), hemorragia de la 2da mitad del embarazo (OR=0,80; IC95%=0,71-0,92), ruptura prematura de membranas (OR=0,83; IC95%=0,79-0,87), amenaza de parto pretérmino (OR=0,87; IC95%=0,80-0,94) y desgarro vaginal (OR= 0,86; IC95%=0,79-0,93). Conclusión: el embarazo se comporta como factor de riesgo para ciertas complicaciones obstétricas en la población adolescente, especialmente en las adolescentes tempranas. Existen además otros factores, que sumados a la edad materna, constituyen la necesidad de formar equipos multidis-ciplinarios para reducir complicaciones obstétricas en esta población. / Revisión por pares