Objective: Reductions in sodium pump (SP) abundance can give rise to increases in contractile force in uterine and vascular smooth muscle as well as an increased secretion in secretory cells, including potentially those of the placenta. To determine whether the mouse might serve as a model for human pregnancy in terms of the SP and to determine whether changes in SP abundance anticipate or follow labor, we studied pregnant mice over the final trimester of their pregnancy. Study Design: C57Bl6 dams (n=46) were bred and studied during their pregnancy. Animals (n=4) were sacrificed at specific gestational time points. Other mice had labor induced with LPS on Gestational day 15 and were then studied at specific time points after induction. Specimens were studied for mRNA abundance as well as protein abundance using methods such as Real time RT-PCR and Western blot analysis. Data were analyzed by ANOVA with post hoc Duncan's pair-wise comparisons. Results: Levels of uterine SP α3 isoform mRNA were most abundant on day 14 near the beginning of the third trimester. There was a significant fall in SP &alpha3 mRNA abundance by day 18 with a slightly lower level on the day of birth but an increased SP α3 mRNA abundance by one day post partum. Contrary to the uterus, SP α3 mRNA levels in the placenta increased over the last trimester, from day 14 to the day of birth. Western blot analysis on the two tissues demonstrated a somewhat similar pattern. In the LPS studies of uterus and placenta, the SP α3 isoform protein abundance appeared to fall when compared to the 2 hour time point. Those animals which were injected with a vehicle control showed very little change in SP α3 abundance after injection. While protein levels were reduced, there was no significant reduction in mRNA for all specimens. Conclusion: Uterine SP α3 isoform protein expression fell late in mouse pregnancy but prior to labor and appeared to be mediated by reductions in its mRNA. These reductions paralleled changes observed in term pregnant women. Such reductions would increase the sensitivity of the uterus to agents causing contraction but may directly increase the force, duration and frequency of contractions. Placental SP α3 isoform protein expression had no significant change over the final trimester. However, unlike uterine protein, the placental protein may not be mediated by its mRNA. Reductions in SP α3 protein abundance were also seen in preterm labor produced by LPS induction. These changes may not be mediated by mRNA. Taken together, changes in the SP α3 isoform may represent a fundamental mechanism in the initiation and/ or progression of term labor and in preterm in mouse and potentially in human.

No description available.

Increasing evidence implicates the presence of bacteria in intrauterine tissues as an important risk factor for spontaneous preterm labor. Epigenetic alterations of innate immunity genes may increase the mother’s sensitivity to subclinical levels of bacteria. This study examined the presence of TET2, TLR-2, and TLR-9 in intrauterine tissue, and evaluated whether epigenetic alterations of these genes, as well as IL-8, changed their expression in human decidual tissue and a macrophage cell culture. Immunohistochemicalstaining was used to detect the presence of these proteins in intrauterine tissue. Gene expression changes were evaluated in stimulated monocytes and macrophages. Fluorescence immunohistochemistry was used to track translocation of TET2 in stimulated monocytes and macrophages. Secreted IL-8 concentration was detected with ELISA. Decidual expression of TET2, TLR-2, and TLR-9 increased in the order TNL < TL < sPTL < iPTL. This study found that TET2, TLR-2, TLR-9, and IL-8 are regulated by epigenetic mechanisms. This study was the first to report activation of TET2 involves its translocation from the cytosol to the nucleus in macrophages.

Modélisations moléculaires réalisés avec le logiciel HyperChem 8. / L’effet de différentes alkylations sur l’activité biologique et la stabilité enzymatique d’un peptide linéaire L, énantiomère du modulateur allostérique des récepteurs prostaglandine F2α ont été étudiés. Dans une étude antérieure, le peptide D PDC-31 avait montré un potentiel d’inhibition des contractions du myomètre et permettait de retarder l’accouchement dans des modèles animaux et humains. Il est possible que le peptide L possède une activité semblable, mais les protéases, abondantes dans le tissu myométrial, le dégradent probablement avant qu’il ne puisse atteindre le site actif. La synthèse peptidique sur support solide suivie d’une amination réductive a permis d’obtenir différents peptides portant différentes chaines alkyle et PEG N-terminales. La protection de l’amine terminale par un groupement ortho-nitrobenzène sulfonyle suivie par une réaction de Mitsunobu a permis l’obtention d’un analogue portant une chaine farnesyle. Malgré le fait que ni l’analogue PEGylé, ni l’analogue farnesylé n’aient montrés la moindre activité, certains analogues alkylés se sont avérés actifs dans l’essai tissulaire de contractions myométriales. Le peptide L portant une chaine dodecyle s’est avéré posséder une activité statistiquement significative et reproductible. Qui plus est, l’analogue D du peptide possédant une chaine de 12 carbones s’est avéré posséder une activité inférieure à l’analogue L portant la même chaine, ce qui représente une perte d’activité significative par rapport au peptide D nonmodifié (PDC-31). / The application of hydrophobic grafts to prolong the biological activity of rapidly metabolized peptides has been explored by modification of the L-peptide of the prostaglandin F2α receptor modulator PDC-31. The all-D peptide PDC-31 has previously been shown to inhibit myometrial contractions and delay labour in various animal models as well as in humans. The L-peptide may have activity; however, proteases, which are abundant in myometrial tissue, may likely degrade the peptide before it is capable of showing activity. Solid-phase peptide synthesis followed by Nterminal modification by reductive aminations with different aldehydes provided linear aliphatic alkyl and PEG-grafted peptide analogs. Alternatively, ortho-nitrobenzensulfonylation of the peptide followed by Mitsunobu alkylation with farnesol and deprotection gave a farnesylated analog. Although the PEG and fanesylated analogs exhibited no activity, certain N-alkyl analogs exhibited inhibitory activity on myometrial contractions, with the most active analog possessing a dodecyl chain. Moreover, the N-dodecyl analog of PDC-31, exhibited lower activity than its L-counterpart in the myometrial contraction assay, and with reduced potency relative to its unmodified structure.

Introdução: Há tempos Micoplasmas Genitais como o Ureaplasma vêm sendo implicados na patogênese de trabalho de parto prematuro e morbidade neonatal, mas seu real papel permanece obscuro e sua prevalência no sangue de recém-nascidos de muito baixo peso ainda não foi estudada em nosso meio. Objetivo: Determinar a prevalência da infecção por Ureaplasma urealyticum (Uu) e Ureaplasma parvum (Up) em uma amostra de recém-nascidos de muito baixo peso (RNMBP) e avaliar os fatores associados. Pacientes e métodos: Foi realizada extração de DNA de amostras de sangue de RNMBP coletadas nas primeiras 72 horas de vida e a presença de Uu e/ou Up foi identificada por técnica de Reação em Cadeia de Polimerase (PCR). Os recém-nascidos foram acompanhados até a alta hospitalar. Resultados: Noventa e cinco recém-nascidos de muito baixo peso foram incluídos no estudo. A detecção de Uu e/ou Up ocorreu em 12 recém-nascidos (12,63%). Em 5,26% foi detectado somente Uu, em 5,26% somente Up e em 2,11% ambos. Na análise univariada a presença de Ureaplasma foi associada à infecção ovular e a trabalho de parto prematuro. Pré-eclâmpsia e ser PIG foram associados a menor ocorrência de Ureaplasma. Quando analisados apenas os nascimentos decorrentes de trabalho de parto prematuro, a prevalência da infecção por Ureaplasma foi de 25%. Pela regressão logística passo a passo, somente trabalho de parto prematuro manteve-se estatisticamente significante aumentando em 9 vezes a chance de positividade para Ureaplasma. Conclusão: A infecção por Ureaplasma é comum em recém-nascidos de muito baixo peso, principalmente entre os nascidos de trabalho de parto prematuro, reforçando a hipótese de associação entre prematuridade e infecção por Ureaplasma. / Introduction: Ureaplasma has long been implicated in the pathogenesis of both preterm labor and neonatal morbidity, but its actual role remains unclear, and it’s prevalence in the blood of very low birth weight (VLBW) infants has not been studied in our country. Objective: To determine the prevalence of Ureaplasma urealyticum (Uu) and Ureaplasma parvum (Up) bacteremia in a sample of very low birth weight infants and evaluate the associated factors. Patients and methods: DNA was extracted from blood samples collected during the first 72 hours of life of VLBW infants and the presence of Uu and/or Up was identified by the technique of Polymerase Chain Reaction (PCR). The newborns were followed up until hospital discharge. Results: Ninety-five very low birth weight newborns were included in the study. Detection of Uu and / or Up occurred in 12 infants (12.6%). We detected Uu in 5.2%, Up in 5.2% and both in 2.1%. In univariate analysis the presence of Ureaplasma was associated with clinical chorioamnionitis and preterm labor. Pre-eclampsia and SGA were associated with lower incidence of Ureaplasma. When analyzing only the births due to preterm labor, the prevalence of Ureaplasma bacteremia was 25%. Only preterm labor remained statistically significant after step by step logistic regression analysis increasing by 9 times the chance of Ureaplasma occurrence. Conclusion: Ureaplasma bacteremia is common in very low birth weight infants, especially among those born of premature labor, reinforcing the hypothesis of an association between prematurity and Ureaplasma infection.

Introdução: Há tempos Micoplasmas Genitais como o Ureaplasma vêm sendo implicados na patogênese de trabalho de parto prematuro e morbidade neonatal, mas seu real papel permanece obscuro e sua prevalência no sangue de recém-nascidos de muito baixo peso ainda não foi estudada em nosso meio. Objetivo: Determinar a prevalência da infecção por Ureaplasma urealyticum (Uu) e Ureaplasma parvum (Up) em uma amostra de recém-nascidos de muito baixo peso (RNMBP) e avaliar os fatores associados. Pacientes e métodos: Foi realizada extração de DNA de amostras de sangue de RNMBP coletadas nas primeiras 72 horas de vida e a presença de Uu e/ou Up foi identificada por técnica de Reação em Cadeia de Polimerase (PCR). Os recém-nascidos foram acompanhados até a alta hospitalar. Resultados: Noventa e cinco recém-nascidos de muito baixo peso foram incluídos no estudo. A detecção de Uu e/ou Up ocorreu em 12 recém-nascidos (12,63%). Em 5,26% foi detectado somente Uu, em 5,26% somente Up e em 2,11% ambos. Na análise univariada a presença de Ureaplasma foi associada à infecção ovular e a trabalho de parto prematuro. Pré-eclâmpsia e ser PIG foram associados a menor ocorrência de Ureaplasma. Quando analisados apenas os nascimentos decorrentes de trabalho de parto prematuro, a prevalência da infecção por Ureaplasma foi de 25%. Pela regressão logística passo a passo, somente trabalho de parto prematuro manteve-se estatisticamente significante aumentando em 9 vezes a chance de positividade para Ureaplasma. Conclusão: A infecção por Ureaplasma é comum em recém-nascidos de muito baixo peso, principalmente entre os nascidos de trabalho de parto prematuro, reforçando a hipótese de associação entre prematuridade e infecção por Ureaplasma. / Introduction: Ureaplasma has long been implicated in the pathogenesis of both preterm labor and neonatal morbidity, but its actual role remains unclear, and it’s prevalence in the blood of very low birth weight (VLBW) infants has not been studied in our country. Objective: To determine the prevalence of Ureaplasma urealyticum (Uu) and Ureaplasma parvum (Up) bacteremia in a sample of very low birth weight infants and evaluate the associated factors. Patients and methods: DNA was extracted from blood samples collected during the first 72 hours of life of VLBW infants and the presence of Uu and/or Up was identified by the technique of Polymerase Chain Reaction (PCR). The newborns were followed up until hospital discharge. Results: Ninety-five very low birth weight newborns were included in the study. Detection of Uu and / or Up occurred in 12 infants (12.6%). We detected Uu in 5.2%, Up in 5.2% and both in 2.1%. In univariate analysis the presence of Ureaplasma was associated with clinical chorioamnionitis and preterm labor. Pre-eclampsia and SGA were associated with lower incidence of Ureaplasma. When analyzing only the births due to preterm labor, the prevalence of Ureaplasma bacteremia was 25%. Only preterm labor remained statistically significant after step by step logistic regression analysis increasing by 9 times the chance of Ureaplasma occurrence. Conclusion: Ureaplasma bacteremia is common in very low birth weight infants, especially among those born of premature labor, reinforcing the hypothesis of an association between prematurity and Ureaplasma infection.

Introdução: Há tempos Micoplasmas Genitais como o Ureaplasma vêm sendo implicados na patogênese de trabalho de parto prematuro e morbidade neonatal, mas seu real papel permanece obscuro e sua prevalência no sangue de recém-nascidos de muito baixo peso ainda não foi estudada em nosso meio. Objetivo: Determinar a prevalência da infecção por Ureaplasma urealyticum (Uu) e Ureaplasma parvum (Up) em uma amostra de recém-nascidos de muito baixo peso (RNMBP) e avaliar os fatores associados. Pacientes e métodos: Foi realizada extração de DNA de amostras de sangue de RNMBP coletadas nas primeiras 72 horas de vida e a presença de Uu e/ou Up foi identificada por técnica de Reação em Cadeia de Polimerase (PCR). Os recém-nascidos foram acompanhados até a alta hospitalar. Resultados: Noventa e cinco recém-nascidos de muito baixo peso foram incluídos no estudo. A detecção de Uu e/ou Up ocorreu em 12 recém-nascidos (12,63%). Em 5,26% foi detectado somente Uu, em 5,26% somente Up e em 2,11% ambos. Na análise univariada a presença de Ureaplasma foi associada à infecção ovular e a trabalho de parto prematuro. Pré-eclâmpsia e ser PIG foram associados a menor ocorrência de Ureaplasma. Quando analisados apenas os nascimentos decorrentes de trabalho de parto prematuro, a prevalência da infecção por Ureaplasma foi de 25%. Pela regressão logística passo a passo, somente trabalho de parto prematuro manteve-se estatisticamente significante aumentando em 9 vezes a chance de positividade para Ureaplasma. Conclusão: A infecção por Ureaplasma é comum em recém-nascidos de muito baixo peso, principalmente entre os nascidos de trabalho de parto prematuro, reforçando a hipótese de associação entre prematuridade e infecção por Ureaplasma. / Introduction: Ureaplasma has long been implicated in the pathogenesis of both preterm labor and neonatal morbidity, but its actual role remains unclear, and it’s prevalence in the blood of very low birth weight (VLBW) infants has not been studied in our country. Objective: To determine the prevalence of Ureaplasma urealyticum (Uu) and Ureaplasma parvum (Up) bacteremia in a sample of very low birth weight infants and evaluate the associated factors. Patients and methods: DNA was extracted from blood samples collected during the first 72 hours of life of VLBW infants and the presence of Uu and/or Up was identified by the technique of Polymerase Chain Reaction (PCR). The newborns were followed up until hospital discharge. Results: Ninety-five very low birth weight newborns were included in the study. Detection of Uu and / or Up occurred in 12 infants (12.6%). We detected Uu in 5.2%, Up in 5.2% and both in 2.1%. In univariate analysis the presence of Ureaplasma was associated with clinical chorioamnionitis and preterm labor. Pre-eclampsia and SGA were associated with lower incidence of Ureaplasma. When analyzing only the births due to preterm labor, the prevalence of Ureaplasma bacteremia was 25%. Only preterm labor remained statistically significant after step by step logistic regression analysis increasing by 9 times the chance of Ureaplasma occurrence. Conclusion: Ureaplasma bacteremia is common in very low birth weight infants, especially among those born of premature labor, reinforcing the hypothesis of an association between prematurity and Ureaplasma infection.

The purpose of this research project was to elucidate the molecular interactions and detail the signaling pathways in obstetric pathologies. This work first seeks to understand inflammation related complications relevant to obstetrics. Prior research in our lab identified the implications of the receptor of advanced glycation end products (RAGE) during inflammatory response in the placenta. Current work identified the presence of DNA double-strand breaks (DNA-DSBs) in inflammation associated pregnancy complications of preeclampsia (PE) and preterm labor (PTL) and demonstrated the positive role of RAGE in repairing the damage. The confluent relevance of disrupted mitochondrial function and inflammation has been recognized in the etiology of numerous chronic diseases. Our current studies aim to understand the connections between energy metabolism and inflammation in pathologies of pregnancy complications. Previous research conducted in our laboratory has demonstrated the mediation of the Gas6/Axl pathway on the mechanistic target of rapamycin (mTOR), an important metabolic molecule. We observed the negative regulation of Gas6 treatment on the mTOR pathway and its negative effects on trophoblast cell invasion. In the current study looking at the aspect of energy regulation, we identified the activation of placental mTOR in gestational diabetes mellitus (GDM) and its decrease during PE and intrauterine growth restriction (IUGR). We further evaluated the regulation of mTOR on its downstream effector pyruvate kinase M2 (PKM2). We found that inhibition of mTOR decreased PKM2 activation; while PKM2 activation positively regulated trophoblastic invasion and rescued negative effects observed in our second-hand smoke IUGR murine model. Our work has opened a new direction of placental research, especially in pregnancy complications stemming from genomic instability. We also clarified details of mTOR and PKM2 meditated metabolic signaling that are crucial for future investigation on the dynamic metabolic regulation during pregnancy.

Introdução: Prematuridade é a principal causa de morbimortalidade perinatal. A aplicação de um instrumento que identifique o grupo de pacientes de risco para parto pré-termo (PPT) permitirá a aplicação de estratégias de prevenção e reduzirá essa complicação. Objetivos: validar a calculadora de risco para PPT espontâneo antes da 34ª semana de gestação, disponibilizada pela Fetal Medicine Foundation (FMF), em uma amostra de mulheres brasileiras. Métodos: Estudo retrospectivo, observacional que analisou 1325 gestantes admitidas para seguimento pré-natal. Variáveis maternas de interesse foram coletadas por meio da análise de questionários, prontuários e contato telefônico. Em seguida, os dados foram inseridos na calculadora para cálculo do risco de PPT. As gestantes foram divididas em dois grupos de acordo com a ocorrência de PPT antes da 34ª semana (Grupo 1) ou parto após 37 semanas de gestação (Grupo 2). Análise de regressão múltipla foi efetuada para avaliar os efeitos das variáveis estudadas sobre a ocorrência de parto pré-termo antes da 34ª semana e para a construção de um modelo de discriminação, que foi avaliado pelo índice c. Curva ROC foi utilizada para os cálculos de sensibilidade e especificidade e, com base nesses valores, do valor de corte acima do qual o risco de PPT antes de 34 semanas foi significativamente maior em nossa amostra de pacientes. Resultados: A prevalência de PPT espontâneo antes da 34ª semana foi de 1.3%. As variáveis que apresentaram diferenças significativas entre os Grupos 1 e 2 foram: tabagismo (p=0,0002), antecedente de prematuridade de prematuridade repetitiva entre 16 - 30 semanas sem parto prévios a termo e de prematuridade eletiva (p<0,0001 e p=0,0271, respectivamente) e risco calculado de PPT antes de 34 semana (1.32% X 0.78%, p<0,01). A regressão múltipla confirmou que o tabagismo e os antecedentes de PPT aumentaram o risco de PPT espontâneo em nossa amostra. Na avaliação do desempenho do teste índice para detectar PPT antes de 34 semanas, observou-se área sob a curva significante de 0.64 e o ponto de corte acima do qual o risco de PPT aumenta significativamente foi 0.7%. Conclusões: a calculadora de risco de PPT antes da 34ª semana da FMF é um bom instrumento para rastrear gestantes em nossa amostra populacional e o valor de corte acima do qual esse risco aumenta é 0.7%. / Introduction: Prematurity is the leading cause of perinatal morbidity and mortality. The use of an instrument to identify the group of patients at risk for preterm birth (PTB) will allow the implementation of prevention strategies, therefore reducing this complication. Objectives: To validate the calculator for assessment of risk for spontaneous delivery before 34 weeks of pregnancy, provided by the Fetal Medicine Foundation (FMF) for a group of Brazilian women. Methods: This retrospective and observational cohort study comprised 1,325 women undergoing routine antenatal care. Maternal variables were collected through the analysis of questionnaires, medical records and telephone calls. Then the data were inserted in the software to calculate the risk of PTB. The patients were divided in two groups according to the occurrence of PTB before 34 weeks (Group 1) or birth after 37 weeks of pregnancy (Group 2). Multilevel regression analysis was used to determine the effects of maternal characteristics on the occurrence of PTB before 34 weeks and to build a discrimination model which was evaluated by the index c. ROC curve was used to determine sensitivity and specificity, and the cutoff value above which it the risk of PTB before 34 weeks was significantly higher in our patient sample. Results: The prevalence of spontaneous PTB before 34 weeks was 1.3%. Variables that showed significant differences between groups 1 and 2 were: smoking (p=0.0002), history of repetitive PTB between 16-30 weeks without prior term and elective PTB (p<0.0001 and p=0.0271, respectively), and the risk of PTB before 34 week (1.32% vs. 0.78%, p<0.01). Multilevel regression analysis confirmed that smoking and history of PTB increased the risk of spontaneous PTB in our patient sample. On the assessment of performance index test to detect PPT before 34 weeks there was a significant area under the curve of 0.64 and the cutoff above which it the risk of PTB before 34 weeks was significantly higher was 0.7 %. Conclusions: the calculator for assessment of risk for spontaneous delivery before 34 weeks of pregnancy is a good tool for screening pregnant women in our population sample and the cutoff value above which it the risk increases is 0.7%.

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