Clinical procedures for the prevention of preeclampsia in pregnant women: a systematic peview / Procedimentos clínicos para a prevenção de pré-eclâmpsia em gestantes: Uma revisão sistemática

Abstract Objective To identify the most effective procedures recommended for the prevention of preeclampsia. Data Sources A systematic review was performed in the following databases: Pubmed/MEDLINE, CINAHL, Web of Science, Cochrane and LILACS via the Virtual Health Library (VHL). A manual search was also performed to find additional references. The risk of bias, the quality of the evidence, and the classification of the strength of the recommendations were evaluated using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Selection of Studies In the initial search in the databases, the total number of articles retrieved was 351, and 2 were retrieved through the manual search; after duplicate articles were removed, 333 citations remained. After a thorough review of the titles and abstracts, 315 references were excluded. Accordingly, 18 articles were maintained for selection of the complete text (phase 2). This process led to the exclusion of 6 studies. In total, 12 articles were selected for data extraction and qualitative synthesis. Data Collection The articles selected for the study were analyzed, and we inserted the synthesis of the evidence in the online software GRADEpro Guideline Development Tool (GDT) (McMaster University and Evidence Prime Inc. All right reserved. McMaster University, Hamilton, Ontário, Canada); thus, it was possible to develop a table of evidence, with the quality of the evidence and the classification of the strength of the recommendations. Data Synthesis In total, seven studies recommended the individual use of aspirin, or aspirin combined with calcium, heparin or dipyridamole. The use of calcium alone or in combination with phytonutrients was also highlighted. All of the studies were with women at a high risk of developing preeclampsia. Conclusion According to the studies evaluated, the administration of aspirin is still the best procedure to be used in the clinical practice to prevent preeclampsia.

Resumo Objetivo Identificar quais são as condutas recomendadas para a prevenção de pré-eclâmpsia em gestantes. Fontes de Dados Foi feita uma revisão sistemática da literatura, e foram desenvolvidas estratégias detalhadas de busca individual nas bases de dados PubMed/MEDLINE, CINAHL, Web of Science, Cochrane e LILACS pela Biblioteca Virtual em Saúde (BVS). Uma pesquisa manual também foi realizada para encontrar referências adicionais. O risco de viés, a qualidade da evidência, e a classificação da força das recomendações foram avaliadas usando a abordagem Classificação de Recomendações, Avaliação, Desenvolvimento e Análises (Gradings of Recommendations, Assessment, Development and Evaluations, GRADE). Seleção dos Estudos No total, foram encontrados 351 artigos na busca inicial nas bases de dados consultadas e 2 na busca manual; após exclusões por duplicidade, 333 artigos permaneceram. Após a leitura de títulos e resumos, 315 referências foram excluídas. Portanto, 18 artigos foram mantidos para a seleção do texto completo (fase 2); esse processo levou à exclusão de 6 artigos. Após as exclusões por incompatibilidade com os critérios de inclusão, 12 artigos compuseram a amostra. Coleta de Dados Os artigos selecionados para o estudo foram analisados, e a digitação da síntese das evidências foi realizada no software online GRADEpro Guideline Development Tool (GDT) (McMaster University and Evidence Prime Inc. Todos os direitos reservados. McMaster University, Hamilton, Ontário, Canadá), o que possibilitou a elaboração de uma tabela de evidências, com a qualidade das evidências e a classificação da força das recomendações. Síntese dos Dados No total, sete estudos recomendaram o uso individual de aspirina, ou aspirina combinada com cálcio, heparina ou dipiridamol. O uso de cálcio isolado ou em combinação com fitonutrientes também foi destacado. Todos os estudos foram realizados com mulheres com alto risco de desenvolver pré-eclâmpsia. Conclusão De acordo com os estudos avaliados, a administração de aspirina ainda é a melhor conduta a ser utilizada na prática clínica para prevenir a pré-eclâmpsia.

Prediction of preterm pre-eclampsia at midpregnancy using a multivariable screening algorithm.

BACKGROUND: Competing risk models used for midpregnancy prediction of preterm pre-eclampsia have shown detection rates (DR) of 85%, at fixed false-positive rate (FPR) of 10%. The full algorithm used between 19+0 and 24+6  weeks includes maternal factors, mean arterial pressure (MAP), mean uterine artery pulsatility index (UtAPI), serum placental growth factor (PlGF) level in multiples of the median (MoM), and soluble Fms-like tyrosine kinase-1 (sFlt-1) level in MoM. AIMS: To assess performance of the Fetal Medicine Foundation (FMF) algorithm at midpregnancy to screen for preterm (<37 weeks) pre-eclampsia. The outcome measured was preterm pre-eclampsia. MATERIALS AND METHODS: This is a prospective study including singleton pregnancies at 19-22 weeks gestation. Maternal bloods were collected and analysed using three different immunoassay platforms. Maternal characteristics, medical history, MAP, mean UtAPI, serum PlGF MoM and serum sFlt-1 MoM were used for risk assessment. DR and FPR were calculated, and receiver operating characteristic curves produced. RESULTS: Five hundred and twelve patients were included. Incidence of preterm pre-eclampsia was 1.6%. Using predicted risk of pre-eclampsia of one in 60 or more and one in 100 or higher, as given by the FMF predictive algorithm, the combination with the best predictive performance for preterm pre-eclampsia included maternal factors, MAP, UtAPI and PlGF MoM, giving DRs of 100% and 100%, respectively, and FPRs of 9.3 for all platforms and 12.9-13.5, respectively. Addition of sFlt-1 to the algorithm did not appear to improve performance. sFlt-1 MoM and PlGF MoM values obtained on the different platforms performed very similarly. CONCLUSIONS: Second trimester combined screening for preterm pre-eclampsia by maternal history, MAP, mean UtAPI and PlGF MoM using the FMF algorithm performed very well in this patient population.

Midpregnancy testing for soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF): An inter-assay comparison of three automated immunoassay platforms.

We performed an inter-assay comparison among three immunoassay platforms for midpregnancy testing of sFlt-1, PlGF and the sFlt-1/PlGF ratio, which are established markers for pre-eclampsia. Maternal blood was collected 19-22 weeks' gestation. Raw data values were converted to multiples of the median (MoM). PlGF and sFlt-1 values among platforms were highly correlated (p < 0.001). There was significant variation in raw data values for PlGF and sFlt-1 among platforms, eliminated following conversion to MoM. When directly comparing raw data values among platforms, platform-specific reference ranges values should be used. MoM values were equivalent among platforms, allowing direct inter-assay result comparison.

Midpregnancy prediction of pre-eclampsia using serum biomarkers sFlt-1 and PlGF.

OBJECTIVES: Pre-eclampsia remains a significant cause of morbidity and mortality. Placental biomarkers soluble Fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) have been investigated previously for their ability to predict pre-eclampsia. We compared the performance of these biomarkers for midpregnancy pre-eclampsia prediction using three different immunoassay platforms. STUDY DESIGN: Prospective study including singleton pregnancies 19-22 weeks' gestation. Maternal bloods were collected at recruitment. Screening performances using receiver operating characteristic (ROC) curves for PlGF and sFlt-1/PlGF ratio raw data and MoM values in isolation were evaluated for three immunoassay platforms using selected cut-off values. MAIN OUTCOME MEASURES: Pre-eclampsia was defined as early-onset (<34 weeks' at delivery) and preterm (<37 weeks' at delivery). RESULTS: For prediction of preterm pre-eclampsia, PlGF MoM and sFlt-1/PlGF ratio MoM performed similarly, with areas under the curve (AUC), detection rates (DR) and false positive rates (FPR) for PlGF MoM and sFlt-1/PlGF ratio MoM being 0.77-0.79 and 0.71-0.74, 62.5% for both and 9.7-14.9 and 10.7-17.7, respectively. For the prediction of early-onset pre-eclampsia, sFlt-1/PlGF ratio raw data and MoM values performed similarly, with AUC, DR and FPR being 0.92-0.97 and 0.93-0.96, 100% for both, and 4.13-16.9 and 9.4-12.2, respectively. CONCLUSIONS: For midpregnancy prediction of preterm pre-eclampsia, PlGF MoM for all three platforms and sFlt-1/PlGF ratio MoM for the two platforms that tested sFlt-1 performed similarly. For midpregnancy prediction of early-onset pre-eclampsia at midpregnancy, sFlt-1/PlGF ratio raw data and MoM values using the early-onset cut-off for the two platforms that tested sFlt-1 gave similar performance from a clinical perspective.

Uterine artery doppler in screening for preeclampsia and fetal growth restriction / Doppler das artérias uterinas no rastreamento para pré-eclâmpsia e restrição do crescimento fetal

Abstract Objective To perform a comprehensive review of the current evidence on the role of uterine artery Doppler, isolated or in combination with other markers, in screening for preeclampsia (PE) and fetal growth restriction (FGR) in the general population. The review included recently published large cohort studies and randomized trials. Methods A search of the literature was conducted usingMedline, PubMed, MeSH and ScienceDirect. Combinations of the search terms "preeclampsia," "screening," "prediction," "Doppler," "Doppler velocimetry," "fetal growth restriction," "small for gestational age" and "uterine artery" were used. Articles in English (excluding reviews) reporting the use of uterine artery Doppler in screening for PE and FGR were included. Results Thirty articles were included. As a single predictor, uterine artery Doppler detects less than 50% of the cases of PE and no more than 40% of the pregnancies affected by FGR. Logistic regression-based models that allow calculation of individual risk based on the combination of multiple markers, in turn, is able to detect ~ 75% of the cases of preterm PE and 55% of the pregnancies resulting in small for gestational age infants. Conclusion The use of uterine artery Doppler as a single predictive test for PE and FGR has poor accuracy. However, its combined use in predictive models is promising, being more accurate in detecting preterm PE than FGR.

Resumo Objetivo Realizar revisão da literatura científica acerca do uso do Doppler das artérias uterinas, de forma isolada ou em combinação com outros marcadores, no rastreamento para pré-eclâmpsia (PE) e restrição do crescimento fetal (RCF) na população geral. A revisão incluiu estudos de coorte e ensaios clínicos randomizados recentemente publicados. Métodos Realizou-se uma pesquisa da literatura nas bases de dados Medline, PubMed, MeSH e ScienceDirect. Diferentes combinações dos termos "preeclampsia," "screening," "prediction," "Doppler," "Doppler velocimetry," "fetal growth restriction," "small for gestational age" e "uterine artery" foram utilizadas. Artigos eminglês, (excluindo-se artigos de revisão) em que o Doppler das artérias uterinas é reportado como ferramenta no rastreamento para PE e RCF foram incluídos. Resultados Trinta artigos foram incluídos. Como teste preditivo isolado, o Doppler das artérias uterinas tem sensibilidade inferior a 50% na detecção de casos de PE e inferior a 40% para identificação de gestações afetadas por RCF. Modelos matemáticos preditivos baseados em equações de regressão logística que permitem o cálculo de risco individual, por sua vez, são mais promissores, permitindo a detecção de 75% dos casos de PE pré-termo, e 55% das gestações que resultarão emparto de recém-nascidos pequenos para a idade gestacional. Conclusão O uso do Doppler das artérias uterinas tem baixa acurácia na identificação de gestações afetadas por PE e RCF. No entanto, seu uso combinado com outros marcadores é mais promissor, apresentando maior acurácia para detecção de PE do que para RCF.

Breast necrosis induced by the use of coumadin: case report and review of literature / Necrose mamária induzida pelo uso de cumarínico: relato de caso e revisão da literatura

The coumadin-induced skin necrosis is rare and occurs more frequently in the breasts, thighs and buttocks. We describe the first case of coumadin necrosis of the breast in Brazil in a 62-year-old patient.

A necrose cutânea induzida por cumarínicos é um evento raro e ocorre com maior frequência nas mamas, coxas e nádegas. Descrevemos o primeiro caso de necrose cumarínica das mamas no Brasil em paciente de 62 anos.

[Preterm birth prediction: sequential evaluation of the cervix and the test for phosphorylated protein-1 linked to insulin-like growth factor]. / Predição do parto prematuro: avaliação sequencial do colo uterino e do teste para proteína-1 fosforilada ligada ao fator de crescimento insulina-símile.

PURPOSE: To investigate the usefulness of the measurement of cervical length and of the test for phosphorylated insulin-like growth factor binding protein-1 (phIGFBP-1) performed sequentially in the prediction of preterm birth and the correlation between tests. METHODS: We analyzed data from 101 asymptomatic pregnant women with a history of premature delivery. The ultrasound measurement of cervical length and phIGFBP-1 test were performed in parallel every three weeks, between 24 and 34 week. The best cutoff value for each cervical evaluation was established by the ROC curve, and the two tests were compared using nonparametric tests. We determined the sensitivity, specificity and predictive values of each test and of the association of the exams for the occurrence of delivery before the 37th weeks. RESULTS: There were 25 preterm births (24.8%). The cervix length showed the highest sensitivity and was able to predict preterm birth in all evaluations, with similar accuracy at different gestational ages. The test for phIGFBP-1 was not helpful at 24 weeks, but was able to predict prematurity when performed at 27, 30 and 33 weeks. The combination of tests increased the sensitivity (81.8%) and negative predictive value (93.7%) when compared to the separate use of each test. The mean cervical length was lower in women with a positive test. CONCLUSIONS: Both cervical length and the test for phIGFBP-1 were able to predict premature delivery, and sequential combination of both tests showed a high sensitivity and high negative predictive value.

Predição do parto prematuro: avaliação sequencial do colo uterino e do teste para proteína-1 fosforilada ligada ao fator de crescimento insulina-símile / Preterm birth prediction: sequential evaluation of the cervix and the test for phosphorylated protein-1 linked to insulin-like growth factor

OBJETIVOS: Averiguar a utilidade da medida do comprimento do colo uterino e do teste para proteína-1 fosforilada ligada ao fator de crescimento insulina-símile (phIGFBP-1), realizados de maneira sequencial, na predição do parto prematuro e a existência de correlação entre os testes. MÉTODOS: Foram submetidos a análise secundária os dados de 101 gestantes assintomáticas com antecedente de prematuridade. A medida ultrassonográfica do comprimento do colo e o teste para phIGFBP-1 foram realizados em paralelo a cada três semanas, entre a 24ª e a 34ª semana. O melhor valor de corte do colo uterino para cada avaliação foi estabelecido por meio de curva ROC, e ambos os testes foram comparados entre si por meio de testes não paramétricos. Foram obtidas a sensibilidade, a especificidade e os valores preditivos de cada teste e da associação dos exames para a ocorrência de parto antes de 37 semanas. RESULTADOS: Houve 25 partos prematuros (24,8%). O comprimento do colo apresentou maior sensibilidade e foi capaz de predizer o parto prematuro em todas as avaliações, com acurácia semelhante em diferentes idades gestacionais. O teste para phIGFBP-1 não foi útil na 24ª semana, porém foi capaz de predizer independentemente a prematuridade na 27ª à 30ª e 33ª semana. A associação dos exames elevou a sensibilidade (81,8%) e o valor preditivo negativo (93,7%) quando comparada à utilização isolada dos testes. O comprimento cervical médio foi menor em gestantes com teste positivo. CONCLUSÕES: Tanto o comprimento cervical quanto o teste para phIGFBP-1 foram capazes de predizer independentemente o parto prematuro, e a associação sequencial de ambos os exames apresentou elevada sensibilidade e alto valor preditivo negativo.

PURPOSE: To investigate the usefulness of the measurement of cervical length and of the test for phosphorylated insulin-like growth factor binding protein-1 (phIGFBP-1) performed sequentially in the prediction of preterm birth and the correlation between tests. METHODS: We analyzed data from 101 asymptomatic pregnant women with a history of premature delivery. The ultrasound measurement of cervical length and phIGFBP-1 test were performed in parallel every three weeks, between 24 and 34 week. The best cutoff value for each cervical evaluation was established by the ROC curve, and the two tests were compared using nonparametric tests. We determined the sensitivity, specificity and predictive values of each test and of the association of the exams for the occurrence of delivery before the 37th weeks. RESULTS: There were 25 preterm births (24.8%). The cervix length showed the highest sensitivity and was able to predict preterm birth in all evaluations, with similar accuracy at different gestational ages. The test for phIGFBP-1 was not helpful at 24 weeks, but was able to predict prematurity when performed at 27, 30 and 33 weeks. The combination of tests increased the sensitivity (81.8%) and negative predictive value (93.7%) when compared to the separate use of each test. The mean cervical length was lower in women with a positive test. CONCLUSIONS: Both cervical length and the test for phIGFBP-1 were able to predict premature delivery, and sequential combination of both tests showed a high sensitivity and high negative predictive value.

Análise citogenética em material de abortamento espontâneo / Cytogenetic analysis of material from spontaneous abortion

OBJETIVO: Descrever as anormalidades cromossômicas em material de abortamento espontâneo. MÉTODOS: Realizou-se compilação retrospectiva da análise de cariótipo em lâmina corada com Banda G por microscopia óptica e em material de 428 produtos de abortamento encaminhados para estudo. RESULTADOS: Foram observados 145 resultados normais (33,9 por cento) e 237 resultados anormais (55,4 por cento). Em 46 amostras não houve crescimento celular (10,7 por cento). As anormalidades numéricas foram as mais frequentes, destacando-se a trissomia do 16 (41 casos), a triplodia (27 casos), a monossomia do X (26 casos), a tetraploidia (13 casos) e a trissomia do 15 (13 casos). CONCLUSÃO: As alterações citogenéticas representam importante causa de perdas gestacionais e sua detecção auxilia o aconselhamento genético do casal. A trissomia do cromossomo 16 é a alteração mais frequentemente encontrada.

OBJECTIVE: To describe chromosomal abnormalities in spontaneous abortion material. METHODS: A retrospective compilation of karyotype analysis of slides stained with Band G was carried out by optical microscopy with materials of 428 abortion products referred for study. RESULTS: There were 145 normal results (33.9 percent) and 237 abnormal results (55.4 percent). In 46 samples there was no cell growth (10.7 percent). Numerical abnormalities were the most frequent, especially trisomy 16 (41 cases), triplodia (27 cases), monosomy X (26 cases), tetraploidy (13 cases) and trisomy 15 (13 cases). CONCLUSION: Cytogenetic alterations are an important cause of pregnancy loss and their detection helps the genetic counseling to the couple. Trisomy 16 is the most often found change.