The ophthalmic artery resistive index as a predictor of choriocapillaris ischemia in multivariate logistic models / Índice de resistência da artéria oftálmica como preditor de isquemias focais da coriocapilar em modelos logísticos multivariados

ABSTRACT Objective Vascular findings in preeclampsia are usually attributed to increased vascular tone. Recently, however, important studies have improved the understanding of the main pathophysiological events in this condition, especially vascular brain remodeling, impaired autoregulation, and damage of the blood-brain barrier, which are well recognized features of cerebral overperfusion. Methods In this study, the association between choriocapillaris ischemia with ophthalmic artery blood flow parameters on orbital Doppler ultrasound is reported for the first time using multivariate logistic models. Multivariate logistic models with ophthalmic artery blood flow parameters, as well as major clinical and laboratory predictive variables were established for choriocapillaris ischemia and choriocapillaris ischemia with retinal detachment. Results In a series of 165 patients, 46 (28%) presented choriocapillaris ischemia; among them, 20 (12%) presented associated retinal detachment. The ophthalmic artery resistive index was the main predictor for choriocapillaris ischemia and choriocapillaris ischemia with retinal detachment in multivariate logistic models. Ophthalmic artery resistance lower than 0.56 was associated with a significantly high incidence of both outcomes. Conclusion This study supports that the branching pattern of choroidal arterioles and the lobular organization of choriocapillaris are the major morphological aspects underlying endothelial damage and lobular ischemia in the context of choroidal overperfusion. Overperfused lobules bordering areas of choriocapillaris ischemia produce a perfusion pressure gradient, with lobular reperfusion, leakage from reperfused choriocapillaris, and retinal detachment. Ophthalmic artery-resistive index lower than 0.56 is proposed as a major predictor of the overperfusion-related choriocapillaris ischemia and choriocapillaris ischemia with retinal detachment in preeclampsia.

RESUMO Objetivo Os achados vasculares na pré-eclâmpsia são usualmente atribuídos ao aumento do tônus vascular. Recentemente, no entanto, importantes estudos têm melhorado a compreensão dos principais eventos fisiopatológicos nessa condição, especialmente o remodelamento vascular cerebral, a perda de autorregulação e a ruptura da barreira hematoencefálica, características bem reconhecidas de hiperperfusão cerebral. Métodos Neste estudo, a associação entre a isquemia da coriocapilar e parâmetros de fluxo sanguíneo da artéria oftálmica no Doppler orbitário é relatada pela primeira vez por meio de modelos logísticos multivariados. Modelos logísticos multivariados com parâmetros de fluxo sanguíneo de artéria oftálmica, assim como os principais preditores clínicos e laboratoriais, foram estabelecidos para isquemia da coriocapilar e coriocapilar associada a descolamento de retina. Resultados Em uma série de 165 pacientes, 46 (28%) apresentaram isquemia da coriocapilar; dentre eles, 20 (12%) apresentaram descolamento de retina associado. O índice de resistência da artéria oftálmica foi o principal preditor para isquemia da coriocapilar e isquemia da coriocapilar associada a descolamento de retina em modelos logísticos multivariados, e índice de resistência da artéria oftálmica menor que 0,56 foi associado a uma incidência significativamente elevada de ambos os desfechos. Conclusão Este estudo sustenta que o padrão de ramificação das arteríolas coroidianas e a organização lobular da coriocapilar são os principais aspectos morfológicos subjacentes ao dano endotelial e à isquemia lobular no contexto do hiperfluxo coroidiano. O hiperfluxo de lóbulos adjacentes às áreas de isquemia da coriocapilar estabelece um gradiente de pressão de perfusão, o que produz reperfusão lobular, extravasamento a partir de coriocapilares reperfundidos e descolamento da retina. O índice de resistência da artéria oftálmica inferior a 0,56 é proposto como um importante preditor de isquemia da coriocapilar e isquemia da coriocapilar associada a descolamento de retina relacionados ao hiperfluxo na pré-eclâmpsia.

Cystatin C as an indicator of renal damage in pre-eclampsia.

OBJECTIVE: To assess the predictive abilities of serum and urinary cystatin C levels for glomerular lesions in pregnant women with pre-eclampsia. METHODS: In this study, kidney function markers were compared between38 pregnant women with pre-eclampsia and 22 healthy pregnant women. RESULTS: The serum and urine levels of cystatin C and urea were significantly higher in the pre-eclampsia group than in the control group. Receiver operating characteristic curve analysis demonstrated that the serum cystatin C level (91.7%) had a superior diagnostic accuracy for pre-eclampsia than the other markers. CONCLUSION: Serum cystatin C level maybe a significant marker of pre-eclampsia.

Longitudinal evaluation of uterine perfusion, endothelial function and central blood flow in early onset pre-eclampsia.

OBJECTIVES: Physiopathological mechanisms that trigger clinical manifestations in pre-eclampsia (PE) remain unclear, and management is still a challenge. The identification of tools to predict the onset of the disease and prevent its complications is of great interest in medical practice. The present study aims to evaluate uterine perfusion, endothelial function and central nervous system blood flow in pregnant women with high-risk factors for PE, for comparison of the results between the group of patients who developed early onset PE and those who remained normotensive throughout pregnancy. STUDY DESIGN: Sixty-two patients were recruited from our high-risk prenatal service, and followed throughout gestation. Patients were submitted to flow-mediated dilation, Dopplervelocimetry of uterine arteries and Dopplervelocimetry of ophthalmic arteries at three distinct moments of pregnancy: between 16+0 and 19+6weeks, between 24+0 and 27+6weeks and at hospital admission to delivery. MAIN OUTCOME MEASURES: Pulsatility index of uterine arteries, flow-mediated dilation and ophthalmic arteries resistance index were evaluated and compared between the two groups of patients. RESULTS: Ten pregnancies were complicated by early onset PE, and these patients presented a significantly higher pulsatility index of uterine arteries between 16+0 and 19+6weeks of gestation, compared with the normotensive group (p=0,016). Both flow-mediated dilation and ophthalmic arteries resistance index values were lower in affected patients at 24+0 to 27+6weeks (p=0,001), and by the time of delivery (p<0,002). CONCLUSIONS: Those findings suggest that impaired placental perfusion, endothelial dysfunction and central hyperperfusion temporarily precede the clinical manifestations of early onset pre-eclampsia.

[Nutritional Status of Pregnant Women under Monitoring in Pre Distinct Prenatal Services: The Metropolitan Area and the Rural Environment]. / Avaliação nutricional de gestantes sob acompanhamento em serviços de pré-natal distintos: a região metropolitana e o ambiente rural.

OBJECTIVE: To determine differences in some nutritional aspects of pregnant women assisted at prenatal care services in a country town and in a metropolitan area. METHODS: Pregnant women received prenatal care in the city of Belo Horizonte (BH), metropolitan area, and Paula Cândido (PC), a country town. A Food Frequency Questionnaire (FFQ) containing socioeconomic information and information about eating habits was applied. In addition,weight and height were measured on the occasion of the visits and the women were ask to give their prepregnancy weight for subsequent BMI calculation. Data were analyzed according to region and trimester of pregnancy using the SPSS software version 15.0, the t-test to compare averages and the chi-square test of independence, with the level of significance set at 5%. RESULTS: 240 pregnant women were included, 90 from the country town and 150 from the metropolitan area. Of these, most were married (BH = 56.6%; PC = 46.6%) and did not work outside the home (BH = 54.0%; PC = 84.4%). They predominantly had 3-4 meals/ day during the 1st and 2nd quarters (BH = 54.0 and 46%; PC = 66.7 and 63.3%, respectively) and had 5-6 meals/day during Q3 in BH (44%). There was significant weight gain only in the 1st quarter (BH: 58,0%; PC: 53.3%). Weight gain versus eating habits was significant for the variables "lunch or dinner away from home" for the 1st quarter in BH (p = 0.006), "How many times they consume milk" in the 1 st quarter in PC (p = 0.03), and "How many times they consume junk food" in the 3rd quarter in BH (p = 0.009). CONCLUSIONS: Pregnant woman showed proper eating habits in both regions despite the prevalence of pregestational overweight in BH and a low level of education and income, especially in the country town, an indicator that may be unfavorable for the nutrition of pregnant women during this period. Studies of association between eating habits and newborn health will provide more information about nutrition during pregnancy.

Avaliação nutricional de gestantes sob acompanhamento em serviços de pré-natal distintos: a região metropolitana e o ambiente rural / Nutritional Status of Pregnant Women under Monitoring in Pre Distinct Prenatal Services: The Metropolitan Area and the Rural Environment

Objetivo Verificar diferenças em alguns aspectos nutricionais de gestantes acompanhadas em serviço de atenção pré-natal em uma cidade do interior e na região metropolitana. Métodos Foram avaliadas gestantes em atendimento pré-natal na cidade de Belo Horizonte (BH), região metropolitana, e Paula Cândido (PC), interior de MG. Aplicou-se um Questionário de Frequência Alimentar (QFA) contendo informações socioeconômicas e sobre o hábito alimentar, além disso, foramaferidos peso e altura nomomento do atendimento e questionado o peso pré-gestacional, para posterior cálculo do IMC (índice de massa corpórea). A análise dos dados foi dividida por região e trimestre gestacional, utilizando o software SPSS versão 15.0, teste t para comparação de médias e qui-quadrado de independência, com 5% de significância. Resultados Foram incluídas 240 gestantes, sendo 90 do interior e 150 da região metropolitana. Destas, a maioria são casadas (BH = 56,6%; PC = 46,6%), não trabalham fora de casa (BH = 54,6%; PC = 84,4%), predominantemente se alimentam 3 a 4 vezes ao dia no 1° e 2° trimestre (BH = 54,0 e 46,0%; PC = 66,7 e 63,3%, respectivamente) e fazem 5 a 6 refeições ao dia no 3° trimestre em BH (44%). Houve ganho de peso significativo somente no 1° trimestre (BH: 58,0%; PC: 53,33%). Ganho de peso versus hábito alimentar foi significativo para as variáveis "almoça ou janta fora de casa," no 1° trimestre BH (p = 0,006); "quantas vezes consome leite," no 1° trimestre PC (p = 0,03); "quantas vezes consome fastfood," no 3° trimestre BH (p = 0,009). Conclusões As gestantes emambas regiões se alimentam de forma adequada, apesar da prevalência de sobrepeso pré-gestacional em BH e baixo nível de escolaridade e renda, principalmente no interior, indicador que pode ser pouco favorável à nutrição das gestantes neste período. Estudos de associação entre hábito alimentar e saúde do recém-nascido irão contribuir para maiores informações sobre a nutrição no período gestacional.

Objective To determine differences in some nutritional aspects of pregnant women assisted at prenatal care services in a country town and in a metropolitan area. Methods Pregnant women received prenatal care in the city of Belo Horizonte (BH), metropolitan area, and Paula Cândido (PC), a country town. A Food Frequency Questionnaire (FFQ) containing socioeconomic information and information about eating habits was applied. In addition,weight and height were measured on the occasion of the visits and the women were ask to give their prepregnancy weight for subsequent BMI calculation. Data were analyzed according to region and trimester of pregnancy using the SPSS software version 15.0, the t-test to compare averages and the chi-square test of independence, with the level of significance set at 5%. Results 240 pregnant women were included, 90 fromthe country town and 150 from themetropolitan area. Of these,most weremarried (BH = 56.6%; PC = 46.6%) and did not work outside the home (BH = 54.0%; PC = 84.4%). They predominantly had 3-4 meals/ day during the 1st and 2nd quarters (BH = 54.0 and 46%; PC = 66.7 and 63.3%, respectively) and had 5-6 meals/day during Q3 in BH (44%). There was significant weight gain only in the 1st quarter (BH: 58,0%; PC: 53.3%). Weight gain versus eating habits was significant for the variables "lunch or dinner away from home" for the 1st quarter in BH (p = 0.006), "How many times they consume milk" in the 1 st quarter in PC (p = 0.03), and "How many times they consume junk food" in the 3rd quarter in BH (p = 0.009). Conclusions Pregnant woman showed proper eating habits in both regions despite the prevalence of pregestational overweight in BH and a low level of education and income, especially in the country town, an indicator that may be unfavorable for the nutrition of pregnant women during this period. Studies of association between eating habits and newborn health will provide more information about nutrition during pregnancy.

Identification of a Novel Agonist-Like Autoantibody in Preeclamptic Patients.

BACKGROUND: Recent studies have shown that preeclampsia (PE) is associated with the presence of autoantibodies (AABs) that activate the angiotensin II AT1 receptor, which could contribute to many of the symptoms of PE. METHODS: To investigate the frequency and the targets of AABs in preeclamptic women (31 cases) and healthy pregnant normotensive women (29 cases) in Brazil, antibodies from serum samples were detected by a bioassay using spontaneously beating neonatal rat cardiomyocytes in culture. In the cardiomyocytes, the agonistic AABs induce a positive or negative chronotropic response, mimicking the corresponding receptor agonists. The specificity of the AAB response was identified by specific receptor antagonists. RESULTS: Thirty preeclamptic patients (97%) presented AABs against the angiotensin II AT1 receptor. The agonistic effect of the AAB was blocked by irbesartan and neutralized by a peptide corresponding to the second extracellular loop of this receptor. Strikingly, we discovered that all sera from the severe preeclamptic patients (16 cases) contained a novel agonist-like AAB directed against the endothelin-1 ETA receptor in addition to the AABs against the angiotensin II AT1 receptor. This AAB was selectively blocked by the antagonist BQ-123, antagonized by the protein kinase C (PKC) inhibitor Calphostin C and neutralized by peptides corresponding to the second extracellular loop of the endothelin-1 ETA receptor subtype. CONCLUSIONS: We described, for the first time, the presence of endothelin-1 ETA receptor AABs in PE. Our results suggest that the presence of both agonistic AABs may be involved in the pathogenesis of severe PE.

Revisiting HELLP syndrome.

HELLP syndrome was first described in 1982 by Weinstein et al. and the term HELLP refers to an acronym used to describe the clinical condition that leads to hemolysis, elevated liver enzymes and low platelets. The syndrome frequency varies from 0.5 to 0.9% pregnancies and manifests preferentially between the 27th and 37th week of gestation. Approximately 30% of cases occur after delivery. Although the etiopathogenesis of this syndrome remains unclear, histopathologic findings in the liver include intravascular fibrin deposits that presumably may lead to hepatic sinusoidal obstruction, intrahepatic vascular congestion, and increased intrahepatic pressure with ensuing hepatic necrosis, intraparenchymal and subcapsular hemorrhage, and eventually capsular rupture. Typical clinical symptoms of HELLP syndrome are pain in the right upper quadrant abdomen or epigastric pain, nausea and vomiting. However, this syndrome can present nonspecific symptoms and the diagnosis may be difficult to be established. Laboratory tests and imaging exams are essential for differential diagnosis with other clinical conditions. Treatment of HELLP syndrome with corticosteroids, targeting both lung maturation of the fetus is still an uncertain clinical value. In conclusion, three decades after the tireless efforts of Dr. Weinstein to characterize HELLP syndrome, it remains a challenge to the scientific community and several questions need to be answered for the benefit of pregnant women.

Função endotelial e perfusão uterina e em gestações subsequentementecomplicadas por pré-eclâmpsia / Endothelial function and uterine perfusion in subsequentpregnancies complicated by preeclampsia

Introdução: a fisiopatologia da pré-eclâmpsia (PE) baseia-se em deficiência no processo de placentação, associada à disfunção endotelial sistêmica materna. A investigação da ocorrência desses fenômenos, antes do aparecimento das manifestações clínicas da PE, pode constituir-se em novo método propedêutico para sua predição. Objetivos: comparar o processo de placentação e a função endotelial de gestantes de alto risco para desenvolvimento de PE, correlacionando esses achados com o seu desenvolvimento posterior. Pacientes e métodos: 74 gestantesforam submetidas ao exame de dilatação fluxomediada (DFM) da artéria braquial e dopplerfluxometria das artérias uterinas para avaliação da função endotelial e do processo de placentação, respectivamente. Os exames foram realizados entre 16 e 20 semanas de gestação e as pacientes foram acompanhadas até o puerpério.Resultados: 15 pacientes tiveram a gestação complicada por PE e 59 mantiveram-se normotensas até o puerpério. Pacientes que subsequentemente desenvolveram PE apresentaram, entre 16 e 20 semanas de gestação, maiores valores no índice de pulsatilidade das artérias uterinas (p<0,001), mas a análise da DFM não apresentoudiferença em relação às pacientes que se mantiveram normotensas. Conclusão:os dados observados sugerem que a deficiência no processo de placentação precede cronologicamente as manifestações clínicas de PE, o que não ocorre com a disfunção endotelial.

Introduction: the pathophysiology of preeclampsia (PE) is based on a deficiency in the process of placentation associated with systemic maternal endothelial dysfunction. The investigation on the occurrence of these phenomena before the onset of PE clinical manifestations can become a new diagnostic method for its prediction. Objectives:to compare the process of placentation and endothelial function in pregnant women athigh-risk for PE development, correlating these findings with its further development. Patients and methods: 74 pregnant women underwent flow-mediated dilation (DFM) of the brachial artery and Doppler flowmetry of uterine arteries to assess endothelial function and placentation process, respectively. The examinations were performedbetween 16 and 20 weeks of gestation and patients were followed until the postpartum period. Results: 15 patients had pregnancies complicated by PE and 59 remained normotensive until the postpartum period. Patients who subsequently developed PE presented high values of pulsatility index in uterine arteries (p <0.001), between 16 and 20 weeks gestation, however, the analysis of DFM did not show difference compared to patients who remained normotensive.Conclusion: The observed data suggest that deficiency in the placentation process chronologically precedes the clinical manifestations of PE, which does not occurwith endothelial dysfunction.

Síndromes neurológicas durante a gestação / Neurological syndromes during pregnancy

A ocorrência de sintomas neurológicos agudos em gestantes ou puérperas não é incomum. Podem ser causados tanto pela exacerbação de uma doença neurológica pré-existentes quanto por doenças relacionadas com a própria gravidez. O diagnóstico preciso é essencial para o tratamento adequado. Sendo assim, é recomentado acompanhamento multidisciplinar antes, durante e após a gravidez. O objetivo do presente estudo é realizar uma revisão da literatura sobre as principais síndromes neurológicas durante a gravidez, descrevê-las e elucidar como é feito o diagnóstico adequado. Para isso, foi realizada uma busca de artigos na base de dados do Medline, via Pubmed, sendo selecionados artigos publicados nos últimos 10 anos, nas línguas inglesa ou portuguesa. Desse modo, o presente estudo demonstra a importância de saber reconhecer e tratar adequadamente cada uma dessas síndromes, bem como de um acompanhamento em centro de referência, uma vez que as síndromes neurológicas estão relacionadas com morbidade e mortalidade materna.(AU)

The occurrence of acute neurological symptoms in pregnant women and during puerperium is not uncommon. This symptoms can be caused both by the exacerbation of a preexisting neurological disease and illnesses related to the pregnancy itself. The accurate diagnosis is essential for proper treatment. Therefore, it is recommended that a multidisciplinary monitoring before, during and after pregnancy. The aim of this study is to conduct a review of the literature on the main neurological syndromes during pregnancy, describe them and elucidate how is made the proper diagnosis. For this, a search for articles on Medline database, via Pubmed was performed, being selected articles published in the last 10 years, in English or Portuguese languages. Thus, the present study demonstrates the importance of knowing recognize and properly handle each of these syndromes, as well as a follow-up in tertiary centers, once the neurologicalsyndromes are related to maternal morbidity and mortality.(AU)

Disfunção endotelial como um link fisiopatológico entre pré-eclâmpsia e diabetes mellitus gestacional / Endothelial dysfunction as a pathophysiological link between pre-eclampsia and gestational mellitus diabetes

A adaptação fisiológica do organismo materno à gestação inclui principalmente a vasodilatação sistêmica e o aumento do volume sanguíneo para um adequado fluxo sanguíneo placentário. Alterações nesse processo causam o desenvolvimento de doenças potencialmente graves, como a pré-eclâmpsia e o diabetes gestacional. Apesar de serem diferentes entre si, vários estudos vêm apontando uma alteração em comum, que é a base do desenvolvimento das duas doenças: a lesão endotelial. Há diferenças na forma como essa lesão é desencadeada, mas os produtos liberados a partir dessa alteração promovem vasoconstrição sanguínea e levam à piora da lesão endotelial e do quadro clínico, atuando assim como uma reação em cadeia. São mostrados nesse estudo as alterações sofridas no endotélio, o ponto de convergência na fisiopatologia da pré-eclâmpsia e do diabetes gestacional, e as várias formas de avaliação clínica dessa lesão, que podem ser usados para detecção precoce dessas doenças e melhor manejo do seu desenvolvimento.(AU)

The physiological adaptation of the maternal organism to pregnancy mainly includes systemic vasodilation and increased blood volume allowing a suitable placental blood flow. Changes in this process may lead to the development of potentially serious diseases, such as pre-eclampsia and gestational diabetes. Although they are different from each other, a variety of studies points out a common event which is the base of development of two diseases: the endothelial injury. There are differences in how this injury is unleashed, but the products released from this lesion promote vasoconstriction and worse of clinical manifestations, acting just like a chain reaction. This study aims to discuss the changes suffered in the endothelium, the most likely point of convergence in the pathophysiology of pre-eclampsia and gestational diabetes, as well as the various forms of clinical assessment of endothelial dysfunction, potential markers of the clinical onset of these gestational diseases.(AU)

Uso de hipoglicemiantes orais em pacientes com Diabetes Mellitus gestacional / Oral hypoglycemic in patients with gestational Diabetes Mellitus

O Diabetes Mellitus Gestacional (DMG) é definido como intolerância a carboidratos com início ou diagnóstico durante a gestação. Em gestantes com DMG, é importante o controle da glicemia a fim de reduzir ou evitar efeitos adversos como abortamento, malformações congênitas e crescimento fetal anormal. Tradicionalmente, a insulina é usada como medicamento de escolha, segura para mãe e feto e eficaz no sentido de controlar os valores glicêmicos maternos. A Metformina é um hipoglicemiante oral que age aumentando a sensibilidade dos tecidos à insulinaNos estudos disponíveis, quando comparada à insulina, a Metformina mostra uma menor taxa de hipoglicemia neonatal grave, porém, não foi observada diferença significativa em relação a outros resultados perinatais, tal como prematuridade. A gliburida é um hipoglicemiante que aumenta a secreção de insulina pelas células beta pancreáticas. É uma droga bem tolerada e apresenta baixa taxa de hipoglicemia materna, em torno de 1,5% das pacientes. A gliburida mostrou eficácia semelhante à insulina em diversos estudos no controle glicemico. Mais estudos clínicos randomizados se fazem necessários no momento atual de discussão sobre os reais benefícios e riscos dessas drogas, a fim de definir seu papel efetivo no tratamento do DMG, consolidando ou não, sua recomendação e seu uso amplo.(AU)

Gestational Diabetes (GMD) is defined as carbohydrate intolerance with onset or first recognition during pregnancy. In pregnants, with GMD the glucose control is important to minimize the risk of miscarriage, fetal congenital malformations and macrossomia. Traditionally, insulin is used, since it does not cross the placenta, being considered safe for the woman and the fetus. Metformin is a hypoglycemic agent that acts as an insulin sensitizer, inhibits gluconeogenesis, suppresses hepatic glucose output and increase intestinal glucose absorption. It crosses the placenta, but it is not considered teratogenic. When compared with insulin, Metformin shows a lower incidence of severe neonatal hypoglycemia, with no difference in rates of other perinatal complications, as prematurity. Glyburide is a hypoglycemic that increases insulin secretion by pancreatic beta cells and sensitivity in peripheral tissues and reducing hepatic clearance of insulin. It shows similar efficacy of insulin on glucose control with a lower rate of maternal hypoglycemia, around 1.5% of patients. The glyburide showed similar efficacy to insulin in several studies in glycemic control. It is still suggested that the use of agent hypoglycemic on DMG can induce a lower maternal weight gain and more treatment adherence. More randomized clinical studies are required to ensure the real benefits and risks of these drugs, in order to define its use on GMD treatment.(AU)

Doppler flowmetry of ophthalmic arteries for prediction of pre-eclampsia / Dopplerfluxometria de artérias oftálmicas para predição de pré-eclâmpsia

Background: central nervous system (CNS) hyperperfusion is one of the events that constitute the pathophysiological basis for the clinical manifestations and complications of pre-eclampsia (PE). Detecting the increased flow in the CNS through Doppler flowmetry of the ophthalmic artery might precede the clinical onset of PE and could be used as a marker for subsequent development of PE. Objective: to evaluate the ophthalmic artery resistive index (OARI) values in the second trimester of pregnancy for prediction of the clinical manifestations of PE. Objective: to evaluate the ophthalmic artery resistive index (OARI) values in the second trimester of pregnancy for prediction of the clinical manifestations of PE. Methods: a total of 73 patients with risk factors for the development of PE were selected from the prenatal service at the HC-UFMG. They were submitted to ophthalmic artery Doppler flowmetry between 24 and 28 weeks of pregnancy and monitored until the end of the pregnancy to verify the occurrence of PE. ROC curves were created to determine the predictive characteristics of the OARI. Results: fourteen of the patients selected developed PE and 59 remained normotensive until the postpartum period. Patients with subsequent development of PE presented OARI values lower than patients that remained normotensive (0.682±0.028 X 0.700±0.029, p=0.044). Considering the development of PE as an outcome, the area under the OARI curve was 0.694 (CI 0.543 to 0.845), with no points obtaining good values of sensitivity or specificity. Conclusion: Doppler flowmetry of ophthalmic arteries between 24 and 28 weeks of pregnancy did not present itself as a good exam for predicting PE. .

Introdução: a hiperperfusão do sistema nervoso central (SNC) é um dos eventos que constitui substrato fisiopatológico para as manifestações clínicas e complicações da pré-eclâmpsia (PE). O fluxo aumentado no SNC, detectado por meio da dopplerfluxometria de artérias oftálmicas, poderia anteceder as manifestações clínicas da PE e, consequentemente, ser utilizado como marcador de subsequente desenvolvimento de PE. Objectivo: avaliar os valores do índice de resistência das artérias oftálmicas (Irao) no segundo trimestre gestacional para a predição das manifestações clínicas da PE. Métodos: pacientes com fatores de risco para desenvolvimento de PE foram selecionadas no serviço de pré-natal do Hospital das Clínicas da Universidade Federal de Minas Gerais (HC-UFMG). Elas foram submetidas à dopplerfluxometria de artérias oftálmicas entre 24 e 28 semanas de gestação e acompanhadas até o final da gestação para averiguar a ocorrência de PE. Curvas ROC foram criadas para determinar as características preditivas do Irao. Resultados: das pacientes selecionadas, 14 desenvolveram PE e 59 mantiveram-se normotensas até o puerpério. Pacientes com subsequente desenvolvimento de PE apresentaram valores de Irao menores do que pacientes que se mantiveram normotensas (0,682±0,028 vs. 0,700±0,029, p=0,044). Ao considerar o desenvolvimento de PE como desfecho, a área sobre a curva do Irao foi de 0,694 (IC 0,543-0,845), sem pontos com bons valores de sensibilidade ou especificidade. Conclusão: a dopplerfluxometria de artérias oftálmicas entre 24 e 28 semanas de gestação não se demonstrou um bom exame para a predição de PE. .

Manejo da crise hipertensiva em gestantes / Management of hypertensive crisis in pregnant women

As doenças hipertensivas na gestação, particularmente a pré-eclâmpsia (PE), respondem por parcela importante da morbidade perinatal e mortalidade materna. O manejo correto, precoce e bem indicado das crises hipertensivas que complicam essas condições obstétricas impactam em importante redução na incidência de sequelas e morte dessas gestantes, podendo, inclusive, impactar em melhora do prognóstico perinatal. Determinar a indicação, os medicamentos, o suporte e a propedêutica complementar que cada gestante com crise hipertensiva deva ser submetida é uma decisão que deve ser baseada em evidências científicas e na experiência de cada serviço com o arsenal farmacológico e propedêutico disponível. Todavia, recomenda-se estabelecer protocolos claros para a abordagem precoce e organizada dessas pacientes. O objetivo do presente estudo é apresentar as evidências existentes no manejo de crises hipertensivas gestacionais, decorrentes da PE, hipertensão arterial crônica ou hipertensão gestacional.(AU)

Hypertensive diseases in pregnancy, particularly pre-eclâmpsia (PE), account for important portion of perinatal morbidity and maternal mortality. The correct management, early and well indicated can positively impact on the hypertensive crises that complicate these obstetric conditions, reducing the incidence of sequelae and death of these pregnant women, and even impact on perinatal prognosis. To determine the indication, the drugs, complementary propedeutics and support that every pregnant women with hypertensive crisis should be submitted is a decision that should be based on scientific evidence and the experience of each service with the pharmacological arsenal available. However, it is recommended to establish clear protocols for the early and organized approach of these patients. The aim of this study is to present the existing evidence in the management of hypertensive crises of PE, chronic hypertension or gestational hypertension.(AU)

Óxido nítrico e arginina di-metil assimétrica: possível via de explicação para o trabalho de parto pré-termo / Nitric oxide and asymmetric dimethyl arginine: a novel pathway to explain preterm labor

O trabalho de parto pré-termo (TPPT) assim como as outras causas de prematuridade respondem pela maior parcela da mortalidade e morbidade neonatal no mundo. Várias vias metabólicas já foram estudadas e diversas alterações já foram encontradas em pacientes que desenvolve TPPT. A via metabólica do óxido nítrico (NO) é reconhecida como um dos possíveis mecanismos de desencadeamento fisiopatológico do TPPT. Níveis elevados de dimetil-arginina assimétrica (ADMA), substância endógena inibidora da NO sintetase, estão relacionados com o desencadeamento de TPPT e com maiores taxas de complicações neonatais. O presente estudo aborda as evidências sobre a relação do TPPT e ADMA e as possíveis aplicações clínicas dessa associação.(AU)

Pre-term labor (PTL), as well as the other causes of prematurity, account for the largest portion of neonatal mortality and morbidity in the world. Several metabolic pathways were studied and a significative number of impairments have already been found in patients who develop PTL. The metabolic pathway of nitric oxide (NO) is recognized as one of the possible mechanisms of pathophysiological PTL?s trigger. High levels of asymmetric dimethyl arginine (ADMA), endogenous inhibitory substance of NO synthetase, are related to the triggering of PTL and with higher rates of neonatal complications. The present study addresses the evidence on the relationship of PTL and ADMA and possible clinical applications of this association.(AU)

Predição de pré-eclâmpsia em suas formas tardia e precoce pela dilatação fluxo-mediada da artéria braquial / Prediction of early and late preeclampsia by flow-mediated dilation of the brachial artery

Objetivo: Avaliar a capacidade de predição das formas precoce e tardia da pré-eclâmpsia pela dilatação fluxo-mediada da artéria braquial (FMD), marcador biofísico de disfunção endotelial. Materiais e Métodos: Um total de 91 pacientes de alto risco para desenvolvimento de pré-eclâmpsia foi submetido a FMD entre 24 e 28 semanas de gestação. Resultados: Das pacientes selecionadas, 19 desenvolveram pré-eclâmpsia, sendo 8 em sua forma precoce e 11 em sua forma tardia. Usando-se um valor de corte de 6,5%, a sensibilidade (S) da FMD para predição de pré-eclâmpsia precoce foi 75,0%, com especificidade (E) de 73,3%, valor preditivo positivo (VPP) de 32,4% e valor preditivo negativo (VPN) de 91,9%. Para predição de pré-eclâmpsia tardia, encontrou-se valor de S de 83,3%, E de 73,2%, VPP de 34,4% e VPN de 96,2%. Para a predição de todas as formas associadas de pré-eclâmpsia, encontrou-se valor de S de 84,2%, E de 73,6%, VPP de 45,7% e VPN de 94,6%. Conclusão: A FMD se mostrou uma ferramenta com boa capacidade de predição de pré-eclâmpsia, nas suas formas tardia e precoce, o que pode representar um impacto positivo no acompanhamento de gestantes de alto risco para desenvolvimento dessa síndrome. .

Objective: To assess the accuracy in the prediction of both early and late preeclampsia by flow-mediated dilation of the brachial artery (FMD), a biophysical marker for endothelial dysfunction. Materials and Methods: A total of 91 patients, considered at high risk for development of preeclampsia were submitted to brachial artery FMD between 24 and 28 weeks of gestation. Results: Nineteen out of the selected patients developed preeclampsia, 8 in its early form and 11 in the late form. With a cut-off value of 6.5%, the FMD sensitivity for early preeclampsia prediction was 75.0%, with specificity of 73.3%, positive predictive value (PPV) of 32.4% and negative predictive value (NPV) of 91.9%. For the prediction of late preeclampsia, sensitivity = 83.3%, specificity = 73.2%, PPV = 34.4% and NPV = 96.2% were observed. And for the prediction of all associated forms of preeclampsia, sensitivity = 84.2%, specificity = 73.6%, PPV = 45.7% and NPV = 94.6% were observed. Conclusion: FMD of the brachial artery is a test with good accuracy in the prediction of both early and late preeclampsia, which may represent a positive impact on the follow-up of pregnant women at high risk for developing this syndrome. .

Assessment of endothelial function in pregnant women with preeclampsia and gestational diabetes mellitus by flow-mediated dilation of brachial artery.

PURPOSE: To compare endothelial function, as assessed by flow-mediated dilation (FMD) in pregnant women with preeclampsia (PE), gestational diabetes mellitus (GDM) and healthy pregnant women. METHODS: We conducted a cross-sectional study of eighty women who were selected and divided into three groups: Group A comprising 42 pregnant women with PE, Group B (control) consisting of 19 normotensive pregnant women with no comorbidities and Group C consisting of 19 pregnant women with GDM. The women underwent FMD and the results were compared between groups. The data were obtained from the Center for Fetal Medicine, Hospital das Clínicas, Federal University of Minas Gerais, Brazil (CEMEFE-HC-UFMG) after approval by the Ethics and Research Committee on June 4, 2008 under no CAAE-0280.0.203.000-08. RESULTS: Nonparametric variance analysis showed no statistically significant difference between the characteristics of the three groups. The comparison between the results of the mean values of brachial artery FMD groups of pregnant women with preeclampsia (FMD = 5.36 ± 4.61 %), gestational diabetes (FMD = 9,18 ± 5.98 %) and pregnant women in the control group (FMD = 17.55 ± 8.35 %) showed that a statistically significant difference was found between groups using the Dunn test. The comparison between groups PE × GDM was not statistically significant. The group consisting of pregnant women with GDM associated with those with PE had significantly lower results for FMD (6.55 ± 5.33 %) than the control group (17.55 ± 8.35 %, p = 0.00). CONCLUSIONS: The group consisting of pregnant women with GDM or PE showed results for FMD significantly lower than the control group, suggesting possible endothelial injury in these patients.

Difference of endothelial function during pregnancies as a method to predict preeclampsia.

BACKGROUND: Systemic endothelial dysfunction has been identified as one of the main events in preeclampsia (PE). A nonhealthy vascular endothelium can be pointed out as the pathophysiological explanation of the clinical manifestations and complications of PE. Once normal pregnancy is characterized by a constant increase in endothelial function, a follow-up of this physiological event could be used as an early marker or a prediction tool to predict PE. OBJECTIVES: To perform a longitudinal assessment of endothelial function, using an ultrasound study of brachial artery flow Flow-mediated dilation (FMD), in normotensive and preeclamptic pregnancies, to evaluate the difference of FMD values along the second trimester of pregnancy to predict PE. PATIENTS AND METHODS: In a prospective cohort study, 91 pregnant women with a high risk of developing PE were subjected to FMD of the brachial artery. The difference in the FMD values, between 16(+0) and 19(+6) and 24(+0) and 27(+6) weeks of gestation were compared, taking PE development into consideration. Receiver operator characteristics (ROC) curves were created to determine the sensibility and specificity of FMD difference to predict PE. RESULTS: A total of 19 patients developed PE and the other 72 women remained normotensive until 1 week after delivery. When considering a cut off of +2.50 %, FMD difference, between the two evaluations, sensitivity for PE prediction was 87.5 % for early onset PE and 95.5 % for late PE. CONCLUSION: The difference of FMD values between the second trimester of pregnancy can be used for PE prediction for both, early and late forms of PE.

Utilização do doppler de artérias uterinas para predição da pré-eclâmpsiaem portadoras de fatores de risco / Use Doppler imaging of uterine arteries for predicting preeclampsia in women with risk factors

Introdução: os distúrbios hipertensivos representam as intercorrências mais frequentes e graves do ciclo grávido-puerperal. Achados anormais no doppler de artérias uterinas, como valores alterados do índice de pulsatilidade médio e persistência da incisura protodiastólica, têm sido propostos como testes de rastreamento adequados para a predição da pré-eclâmpsia. Objetivos: avaliar a capacidade de predizer a ocorrência depré-eclâmpsia pelo doppler das artérias uterinas em grupo de risco clínico e epidemiológico para o seu desenvolvimento. Pacientes e métodos: foram selecionadas 81 gestantes, todas portadoras de fatores de risco para pré-eclâmpsia. As avaliações do índice de pulsatilidade médio foram realizadas nos intervalos gestacionais compreendidos entre 16+0 e 19+6 semanas e 24+0 e 27+6 semanas. Neste último intervalo, foi também avaliada apersistência da incisura protodiastólica bilateral. Resultados: a incisura protodiastólica bilateral entre 24+0 e 27+6 semanas de gestação foi capaz de predizer o diagnóstico de pré-eclâmpsia com 75% de sensibilidade, 82% de especificidade, valor preditivo positivo de 50% e valor preditivo negativo de 93%. A análise dos dados obtidos entre 16+0 e 19+6 semanas de gestação e entre 24+0 e 27+6 semanas de gestação demonstrou que elevados valores de índice de pulsatilidade médio foram encontrados no grupo de pacientes acometidas pela pré-eclâmpsia quando comparado aos encontrados no grupo de pacientes normotensas. Conclusão: as gestações complicadas pela pré-eclâmpsia mostraram prevalência significativamente maior de incisura bilateral e medidas de índice de pulsatilidade médio maiores em cada um dos intervalos estudados. Como nenhum tratamento específico está atualmente disponível, a possibilidade de se predizer a doença, com início ainda na primeira metade da gestação, pode facilitar a monitorização precoce, a instituição de medidas de suporte e a intervenção em momento apropriado para reduzir a morbimortalidade materno-fetal observada na pré-eclâmpsia.

Introduction: Hypertensive disorders represent the most frequent and serious complications of pregnancy and childbirth. Abnormal findings upon uterine artery Doppler, including altered values of pulsatility index and average persistence of bilateral diastolic notch, have been proposed as suitable predictors of preeclampsia in screening tests. Objectives: To evaluate the usefulness of uterine artery Doppler in predicting the occurrence of preeclampsia in a group of women at clinical and epidemiological risk for its development. Patients and methods: 81 pregnant women, all of which with risk factors for developing preeclampsia were selected. The average pulsatility index exams were performed on gestational intervals of 16+0 and 19+6 weeks and 24+0 and 27+6 weeks. In the latter range, the persistence of bilateral diastolic notch was also assessed. Results: Bilateral diastolic notch between 24+0 and 27+6 weeks of gestation could predict the diagnosis of preeclampsia with 75% sensitivity, 82% specificity, positive predictive value of 50% and negative predictive value of 93%. The analysis of data obtained between 16+0 and 19+6 weeks and between 24+0 and 27+6 weeks demonstrated that high values of mean pulsatility index were found in patients affected by preeclampsia compared with those found in the group of normotensivepatients. Conclusion: pregnancies complicated by preeclampsia had significantly higher prevalence of bilateral notches and higher mean pulsatility indexes in each of the ranges studied. Since no specific treatment is currently available, the ability to predict the disease at its onset,in the first half of pregnancy, can facilitate early monitoring, increased support, and the ability to intervene at the appropriate time so as to reduce the maternal-fetal morbidity and mortality observed in preeclampsia.

Prediction of preeclampsia by means of Doppler flowmetry of uterine artery and flow-mediated dilation of brachial artery / Predição de pré-eclâmpsia por meio da dopplerfluxometria das artérias uterinas e da dilatação fluxo-mediada da artéria braquial

Objective To evaluate the association of Doppler of uterine artery and flow-mediated dilation of brachial artery (FMD) in the assessment of placental perfusion and endothelial function to predict preeclampsia. Materials and Methods A total of 91 patients considered as at risk for developing preeclampsia were recruited at the prenatal unit of the authors' institution. All the patients underwent FMD and Doppler of uterine arteries between their 24th and 28th gestational weeks. Calculations of sensitivity and specificity for both isolated and associated methods were performed. Results Nineteen out of the 91 patients developed preeclampsia, while the rest remained normotensive. Doppler flowmetry of uterine arteries with presence of bilateral protodiastolic notch had sensitivity of 63.1% and specificity of 87.5% for the prediction of preeclampsia. Considering a cutoff value of 6.5%, FMD showed sensitivity of 84.2% and specificity of 73.6%. In a parallel analysis, as the two methods were associated, sensitivity was 94.2% and specificity, 64.4%. Conclusion The association of Doppler study of uterine arteries and FMD has proved to be an interesting clinical strategy for the prediction of preeclampsia, which may represent a positive impact on prenatal care of patients considered as at high-risk for developing such a condition. .

Objetivo Avaliar, para a predição de pré-eclâmpsia, a capacidade associada da dopplerfluxometria de artérias uterinas e da dilatação fluxo-mediada da artéria braquial (FMD), como métodos de avaliação da perfusão placentária e da função endotelial. Materiais e Métodos Um total de 91 pacientes consideradas de risco para o desenvolvimento de pré-eclâmpsia foi recrutado do serviço de pré-natal de nossa instituição. Todas foram submetidas a FMD e a dopplerfluxometria de artérias uterinas entre 24 e 28 semanas de gestação. Cálculos de sensibilidade e especificidade dos dois exames isolados e associados foram realizados. Resultados Do total de 91 pacientes recrutadas, 19 desenvolveram pré-eclâmpsia, sendo que as restantes se mantiveram normotensas. Para a predição de pré-eclâmpsia, a dopplerfluxometria de artérias uterinas, através da presença da incisura protodiastólica bilateral, apresentou sensibilidade de 63,1% e especificidade de 87,5%. Considerando um valor de corte de 6,5%, a FMD apresentou sensibilidade de 84,2% e especificidade de 73,6%. Os dois testes associados, em análise paralela, apresentaram sensibilidade de 94,2% e especificidade de 64,4%. Conclusão A associação entre a dopplerfluxometria de artérias uterinas e a FMD mostrou-se uma estratégia interessante para a predição de pré-eclâmpsia, o que pode representar um impacto positivo no acompanhamento pré-natal das pacientes consideradas de risco para pré-eclâmpsia. .

Doppler flowmetry of ophthalmic arteries for prediction of pre-eclampsia.

BACKGROUND: central nervous system (CNS) hyperperfusion is one of the events that constitute the pathophysiological basis for the clinical manifestations and complications of pre-eclampsia (PE). Detecting the increased flow in the CNS through Doppler flowmetry of the ophthalmic artery might precede the clinical onset of PE and could be used as a marker for subsequent development of PE. OBJECTIVE: to evaluate the ophthalmic artery resistive index (OARI) values in the second trimester of pregnancy for prediction of the clinical manifestations of PE. OBJECTIVE: to evaluate the ophthalmic artery resistive index (OARI) values in the second trimester of pregnancy for prediction of the clinical manifestations of PE. METHODS: a total of 73 patients with risk factors for the development of PE were selected from the prenatal service at the HC-UFMG. They were submitted to ophthalmic artery Doppler flowmetry between 24 and 28 weeks of pregnancy and monitored until the end of the pregnancy to verify the occurrence of PE. ROC curves were created to determine the predictive characteristics of the OARI. RESULTS: fourteen of the patients selected developed PE and 59 remained normotensive until the postpartum period. Patients with subsequent development of PE presented OARI values lower than patients that remained normotensive (0.682 ± 0.028 X 0.700 ± 0.029, p = 0.044). Considering the development of PE as an outcome, the area under the OARI curve was 0.694 (CI 0.543 to 0.845), with no points obtaining good values of sensitivity or specificity. CONCLUSION: Doppler flowmetry of ophthalmic arteries between 24 and 28 weeks of pregnancy did not present itself as a good exam for predicting PE.