Prevención de la preeclampsia. Desde la dieta hasta la aspirina: revisión de la literatura

Introducción y objetivo: Explorar las estrategias de prevención de la preeclampsia que se han propuesto a lo largo de la historia. Método: Revisión narrativa de la literatura sobre la evidencia científica histórica disponible entre 2016 y 2023 acerca de la aspirina y otras estrategias de prevención de la preeclampsia, en bases de datos bibliográficas computarizadas de estudios publicados en revistas indexadas. Resultados: Varios estudios confirman la efectividad de la aspirina para prevenir la preeclampsia en población de alto riesgo, siendo un medicamento con bajo riesgo de complicaciones, con mayor evidencia de efectividad si se inicia antes de las 16 semanas de gestación y con un aparente efecto dependiente de la dosis. Intervenciones como la disminución del consumo de sal, el reposo en cama, la suplementación con ácidos grasos, antioxidantes, L-arginina, zinc o magnesio, y el uso de diuréticos o de inhibidores de la bomba de protones, no han mostrado su utilidad en la prevención de la preeclampsia. Conclusiones: La aspirina a dosis baja es un medicamento seguro en el embarazo y efectivo para prevenir la preeclampsia en población de alto riesgo. Es la estrategia de prevención más ampliamente estudiada a lo largo de la historia para la disfunción endotelial durante la gestación.

Introduction and objective: To explore the different prevention strategies for preeclampsia that have been proposed throughout the history. Method: A narrative review of the historical, scientific evidence available between 2016 and 2021 on aspirin and other preeclampsia prevention strategies in computerized bibliographic databases of studies published in indexed journals. Results: Several studies confirm the effectiveness of aspirin to prevent preterm preeclampsia in high-risk populations, considering this as a safe drug with low risk of complications, with greater evidence of effectiveness when started before 16 weeks of gestation and apparently with a dose-dependent effect. Interventions such as reducing salt intake, bed rest, supplementation with fatty acids, antioxidants, L-arginine, zinc, magnesium, the use of diuretics or proton pump inhibitors have not shown its usefulness in the prevention of high risk preeclampsia patients. Conclusions: Low-dose aspirin is a safe drug in pregnancy and is effective to prevent preeclampsia in high-risk populations. Is the most widely studied throughout history prevention strategy for endothelial dysfunction during pregnancy.

Prevención de la preeclampsia y su relevancia en el contexto latinoamericano: una revisión narrativa

La preeclampsia es un trastorno hipertensivo de la gestación que se evidencia durante las últimas semanas de esta. Globalmente, la preeclampsia es la segunda causa de mortalidad materna. Se estima que su incidencia es de aproximadamente un 16% en los países en vías de desarrollo, y llega a superar el 25% en algunos países de Latinoamérica. Se describirán las principales estrategias de prevención de la preeclampsia y su relevancia en el contexto latinoamericano. La búsqueda de información tuvo lugar en PubMed y BVS para las publicaciones realizadas sobre prevención de la preeclampsia, utilizando la expresión de búsqueda (“Disease Prevention” OR “Primary Prevention”) AND (Pre-eclampsia OR Preeclampsia OR “Pre eclampsia”) AND (“Latin America” OR “Central America” OR “South America” OR Caribbean). En PubMed se encontraron 60 y en BVS 42 resultados que responden a la expresión de búsqueda, y fueron seleccionados 18 artículos que discuten estrategias de prevención de la preeclampsia en Latinoamérica. Con estos resultados, se pueden afirmar que, describir las mejores estrategias de prevención de la preeclampsia en Latinoamérica es una tarea pendiente, pues existe una relativa carencia de publicaciones. En consecuencia, se espera que esta revisión motive futuras investigaciones y sea un recurso útil en la actualización médica.

Preeclampsia is a hypertensive disorder of pregnancy that is evident during the last weeks of it. Globally, preeclampsia is the second leading cause of maternal mortality. It is estimated that the incidence is approximately 16% in developing countries, and reaches over 25% in some Latin American countries. The main strategies for the prevention of preeclampsia and their relevance in the Latin American context will be described. The search for information took place in PubMed and BVS for publications on preeclampsia prevention, using the search expression (“Disease Prevention” OR “Primary Prevention”) AND (Pre-eclampsia OR Pre-eclampsia OR “Pre eclampsia”) AND (“Latin America” OR “Central America” OR “South America” OR Caribbean). In PubMed we found 60 and in VHL 42 results that respond to the search expression, and 18 articles were selected that discuss prevention strategies for preeclampsia in Latin America. With these results, it is possible to afirm that describing the best strategies for the prevention of preeclampsia in Latin America is a pending task, since there is a relative lack of publications. Consequently, it is hoped that this review will motivate future research and be a useful resource in medical updating.

Eclampsia atípica tardía: compromiso inusual con proteinuria, pero sin hipertensión / Late atypical eclampsia: unusual involvement with proteinuria, but without hypertension

RESUMEN Paciente primigesta de 27 años, sin antecedentes médicos de importancia y con un apropiado control prenatal, quien recibió atención por parto vaginal a las 39 semanas de gestación con anestesia epidural. Una hora después del parto, presentó cefalea holocraneana a predominio derecho, tratada con antiinflamatorios y relajantes muscular por indicación del servicio de neurología. Horas después de su alta, al tercer día posparto, presentó convulsiones tónico-clónicas bilaterales. Por un examen de orina con proteinuria (+) en tira reactiva y elevaciones discretas de la presión arterial, se solicitó un conteo de proteínas en 24 horas, con valores en 1094,5 mg (valor normal: 0-140). La resonancia magnética con contraste solicitada durante su admisión fue normal, recibiendo tratamiento con fenitoína y sulfato de magnesio durante su hospitalización. Fue dada de alta al quinto día, con controles posteriores por consultorio externo, sin cefalea, proteinuria y/o hipertensión.

ABSTRACT A 27-year-old primigravida patient without a relevant medical history and appropriate prenatal control received attention for vaginal delivery at 39 weeks of gestation. One -hour later, she experienced holocranial headache with right predominance, treated with anti-inflammatories and muscle relaxants by the indication of a neurologist. Hours after her discharge, on the third day post-partum, she developed bilateral tonic-clonic seizures.. Following a urine test in the emergency room with proteinuria (+) in a dipstick, we tested 24-hour protein count in 1094 mg (normal values 0-140). Magnetic resonance with contrast at admission was normal. She received Phenytoin and Magnesium Sulfate during her hospitalization. The evolution was favorable, and he was discharged at five days with ambulatory controls in the medical office without headache, proteinuria, and/or hypertension.

Eucommia granules activate Wnt/β-catenin pathway, and improve oxidative stress, inflammation, and endothelial injury in preeclampsia rats

ABSTRACT Purpose: Pre-eclampsia (PE) is a pregnancy-related complication. Eucommia is effective in the treatment of hypertensive disorders in pregnancy, but the specific effects and possible mechanisms of Eucommia granules (EG) in PE remain unknown. The aim of this study was to investigate the effects and possible mechanisms of EG in PE rats. Methods: Pregnant Sprague Dawley rats were divided into five groups (n = 6): the control group, the model group, the low-dose group, the medium-dose group, and the high-dose group of EG. The PE model was established by subcutaneous injection of levonitroarginine methyl ester. Saline was given to the blank and model groups, and the Eucommia granules were given by gavage to the remaining groups. Blood pressure and urinary protein were detected. The body length and weight of the pups and the weight of the placenta were recorded. Superoxide dismutase (SOD) activity and levels of malondialdehyde (MDA), placental growth factor (PIGF), and soluble vascular endothelial growth factor receptor-1 (sFIt-1) were measured in the placenta. Pathological changes were observed by hematoxylin-eosin staining. Wnt/β-catenin pathway-related protein expression was detected using Western blot. Results: Compared with the model group, the PE rats treated with EG had lower blood pressure and urinary protein. The length and weight of the pups and placental weight were increased. Inflammation and necrosis in the placental tissue was improved. SOD level increased, MDA content and sFIt-1/PIGF ratio decreased, and Wnt/β-catenin pathway-related protein expression level increased. Moreover, the results of EG on PE rats increased with higher doses of EG. Conclusions: EG may activate the Wnt/β-catenin pathway and inhibit oxidative stress, inflammation, and vascular endothelial injury in PE rats, thereby improving the perinatal prognosis of preeclamptic rats. EG may inhibit oxidative stress, inflammation, and vascular endothelial injury through activation of the Wnt/β-catenin pathway in preeclampsia rats, thereby improving perinatal outcomes in PE rats.

Hypertensive disorders during pregnancy as a major cause of preterm birth and adverse perinatal outcomes: findings from a Brazilian National Survey

ABSTRACT Objective This study aimed to evaluate the prevalence of hypertensive disorders during pregnancy among Brazilian women with preterm births and to compare the epidemiological characteristics and perinatal outcomes among preterm births of women with and without hypertension. Methods This was a secondary cross-sectional analysis of the Brazilian Multicenter Study on Preterm Birth. During the study period, all women with preterm births were included and further split into two groups according to the occurrence of any hypertensive disorder during pregnancy. Prevalence ratios were calculated for each variable. Maternal characteristics, prenatal care, and gestational and perinatal outcomes were compared between the two groups using χ2 and t-tests. Results A total of 4,150 women with preterm births were included, and 1,169 (28.2%) were identified as having hypertensive disorders. Advanced maternal age (prevalence ratio (PR) 2.49) and obesity (PR= 2.64) were more common in the hypertensive group. The gestational outcomes were worse in women with hypertension. Early preterm births were also more frequent in women with hypertension. Conclusion Hypertensive disorders of pregnancy were frequent among women with preterm births, and provider-initiated preterm births were the leading causes of premature births in this group. The factors significantly associated with hypertensive disorders among women with preterm births were obesity, excessive weight gain, and higher maternal age.

Descripción de los factores contribuyentes a las muertes secundarias a trastornos hipertensivos asociados al embarazo en Antioquia, Colombia (2012-2020) / Description of the contributing factors to deaths secondary to hypertensive disorders associated with pregnancy in Antioquia, Colombia (2012-2020)

Resumen OBJETIVO: Describir las características de la población afectada y los retrasos que contribuyeron a la mortalidad materna, secundaria a los trastornos hipertensivos del embarazo. MATERIALES Y MÉTODOS: Estudio descriptivo y retrospectivo efectuado con base en la vigilancia epidemiológica de casos centinela de muertes maternas tempranas de mujeres residentes en Antioquia, Colombia, durante el embarazo, el parto y los 42 días siguientes a éste ocurridas en el periodo 2012-2020. Se creó una base de datos en Microsoft Access 2007 (Microsoft, Redmond, WA, USA) y los datos se analizaron en Microsoft Excel y SPSS versión 22. RESULTADOS: Se registraron 266 muertes maternas, de las que 38 fueron secundarias a trastornos hipertensivos del embarazo. La eclampsia fue causa de 15 fallecimientos; 12 por síndrome HELLP, 9 por hemorragia intracerebral y 2 por desprendimiento prematuro de placenta y coagulación intravascular diseminada. En 13 de los 38 casos no hubo una pauta adecuada del sulfato de magnesio, 19 no recibieron tratamiento antihipertensivo, que estaba indicado y 17 no tuvieron un control antihipertensivo adecuado. CONCLUSIÓN: La atención prenatal es una oportunidad decisiva para la detección, prevención y estratificación del riesgo. Todos los centros de atención obstétrica deben estar preparados para gestionar urgencias asociadas con los trastornos hipertensivos del embarazo. Los desenlaces mejoran con la aplicación de protocolos de emergencia estandarizados, organizados y la participación de equipos multidisciplinarios que garanticen una atención de calidad y un efecto positivo en la morbilidad y mortalidad materna susceptible de prevención.

Abstract OBJECTIVE: To describe the characteristics of the affected population and the delays that contributed to maternal mortality secondary to hypertensive disorders of pregnancy. MATERIALS AND METHODS: Descriptive and retrospective study based on the epidemiologic surveillance of sentinel cases of early maternal deaths of women residing in Antioquia, Colombia, during pregnancy, delivery and the 42 days after delivery occurring in the period 2012-2020. A database was created in Microsoft Access 2007 (Microsoft, Redmond, WA, USA), and data were analyzed in Microsoft Excel and SPSS version 22. RESULTS: There were 266 maternal deaths, of which 38 were secondary to hypertensive disorders of pregnancy. Eclampsia was the cause of 15 deaths; 12 due to HELLP syndrome, 9 due to intracerebral hemorrhage, and 2 due to placental abruption and disseminated intravascular coagulation. In 13 of the 38 cases, there was no adequate magnesium sulfate regimen, 19 did not receive indicated antihypertensive treatment, and 17 did not have adequate antihypertensive control. CONCLUSION: Antenatal care is a critical opportunity for detection, prevention, and risk stratification. All obstetric care centers should be prepared to manage emergencies associated with hypertensive disorders of pregnancy. Outcomes improve with the use of standardized, organized emergency protocols and the participation of multidisciplinary teams that ensure quality care and a positive impact on preventable maternal morbidity and mortality.

Early and late-onset preeclampsia: effects of DDAH2 polymorphisms on ADMA levels and association with DDAH2 haplotypes

Abstract Objective: To examine whether the DDAH2 promoter polymorphisms -1415G/A (rs2272592), -1151A/C (rs805304) and -449G/C (rs805305), and their haplotypes, are associated with PE compared with normotensive pregnant women, and whether they affect ADMA levels in these groups. Methods: A total of 208 pregnant women were included in the study and classified as early-onset (N=57) or late-onset PE (N =49), and as normotensive pregnant women (N = 102). Results: Pregnant with early-onset PE carrying the GC and GG genotypes for the DDAH2 -449G/C polymorphism had increased ADMA levels (P=0.01). No association of DDAH2 polymorphisms with PE in single-locus analysis was found. However, the G-C-G haplotype was associated with the risk for late-onset PE. Conclusion: It is suggested that DDAH2 polymorphisms could affect ADMA levels in PE, and that DDAH2 haplotypes may affect the risk for PE.

Síntesis de evidencia y recomendaciones: guías de práctica clínica para el tratamiento farmacológico de la hipertensión arterial en el embarazo / Evidence synthesis and recommendations: clinical practice guidelines on drug treatment for hypertension in pregnancy / Síntese de evidências e recomendações: diretrizes de prática clínica para o tratamento farmacológico da hipertensão arterial na gravidez

RESUMEN Introducción. Los trastornos hipertensivos durante el embarazo son una causa importante de morbilidad grave, muerte y discapacidad a largo plazo. El tratamiento farmacológico adecuado es uno de los pilares de la gestión de estos trastornos. Objetivos. Sintetizar las recomendaciones desarrolladas por la Organización Mundial de la Salud (OMS) con el fin de mejorar la calidad del cuidado y los desenlaces en salud de las mujeres embarazadas con trastornos hipertensivos y abordar aspectos sobre su implementación. Métodos. Se llevó a cabo una síntesis de las recomendaciones de dos guías de la OMS (Tratamiento farmacológico de la hipertensión severa en el embarazo y Tratamiento farmacológico de la hipertensión no severa en el embarazo). Las guías elaboradas por la OMS siguen los métodos de elaboración de las guías GRADE (Grading of Recommendations Assessment Development and Evaluation) del Manual para el Desarrollo de Guías de la OMS. Adicionalmente, se realizó una búsqueda sistemática en PubMed, Lilacs, Health Systems Evidence, Epistemonikos y literatura gris de estudios desarrollados en las Américas con el fin de identificar barreras, facilitadores y estrategias de implementación, así como para identificar indicadores. Resultados. Se formularon cuatro recomendaciones dirigidas a las mujeres con trastornos hipertensivos. Se identificaron barreras y facilitadores para la implementación, y se crearon indicadores de adherencia y resultado. Conclusiones. Las recomendaciones formuladas buscan orientar sobre cómo enfocar el tratamiento farmacológico de la hipertensión en el embarazo, con consideraciones para su implementación en América Latina y el Caribe.

ABSTRACT Introduction. Hypertensive disorders during pregnancy are a major cause of severe morbidity, long-term disability, and death. Appropriate pharmacological treatment is essential in the management of these disorders. Objectives. Synthesize the recommendations developed by the World Health Organization (WHO) to improve the quality of care and health outcomes of adults with high blood pressure, and address aspects of how to implement these recommendations. Methods. A synthesis was conducted of WHO recommendations: drug treatment for severe hypertension in pregnancy and WHO recommendations: drug treatment for non-severe hypertension in pregnancy. The WHO recommendations follow the GRADE methodology (Grading of Recommendations, Assessment, Development, and Evaluation) for the preparation of guidelines, as described in the WHO Handbook for Guideline Development. In addition, a systematic search for studies carried out in the Region of the Americas was conducted in PubMed, Lilacs, Health Systems Evidence, Epistemonikos, and gray literature to identify barriers, facilitators, and implementation strategies. Results. Four recommendations were formulated for women with hypertensive disorders. Implementation barriers and facilitators were identified, and indicators were created to assess adherence and outcomes. Conclusions. The formulated recommendations provide guidance on how to approach drug treatment of hypertension in pregnancy, with considerations for implementation in Latin America and the Caribbean.

RESUMO Introdução. Os distúrbios hipertensivos na gravidez são uma das principais causas do alto índice de morbidade grave, morte e incapacidade de longo prazo. Um dos principais procedimentos para manejo desses distúrbios é o tratamento farmacológico adequado. Objetivos. Apresentar uma síntese das recomendações elaboradas pela Organização Mundial da Saúde (OMS) para melhorar a qualidade da atenção e dos desfechos de saúde em gestantes com distúrbios hipertensivos e abordar aspectos da implementação dessas recomendações. Métodos. Foi elaborado um resumo das recomendações feitas em duas diretrizes da OMS (uma para tratamento farmacológico da hipertensão grave na gestação e outra para tratamento farmacológico da hipertensão não grave na gestação). As diretrizes elaboradas pela OMS seguem os métodos de elaboração da Classificação de Análise, Desenvolvimento e Avaliação de Recomendações (GRADE, na sigla em inglês) do manual de elaboração de diretrizes da OMS. Além disso, foi realizada uma busca sistemática de estudos desenvolvidos na Região das Américas nas bases de dados PubMed, LILACS, Health Systems Evidence e Epistemonikos e na literatura cinzenta, a fim de identificar barreiras, facilitadores e estratégias de implementação, bem como indicadores. Resultados. Foram formuladas quatro recomendações para mulheres com distúrbios hipertensivos. Identificaram-se barreiras e facilitadores para a implementação e criaram-se indicadores de adesão e de resultados. Conclusões. As recomendações formuladas visam orientar a abordagem do tratamento farmacológico da hipertensão na gestação e incluem considerações de implementação na América Latina e no Caribe.

Efeitos da suplementação do cálcio sobre marcadores da pré-eclâmpsia: ensaio clínico randomizado / Efectos de los suplementos de calcio en marcadores de preeclampsia: ensayo clínico aleatorizado / Effects of calcium supplementation on markers of preeclampsia: randomized clinical trial

Resumo Objetivo Analisar os efeitos da suplementação de cálcio nos marcadores da pré-eclâmpsia ao longo do tempo, comparando o uso de cálcio em alta e baixa dosagem em mulheres grávidas com hipertensão. Métodos Trata-se de ensaio clínico randomizado com três grupos paralelos, placebo controlado, realizado no ambulatório de referência para o pré-natal de alto risco na Região Sul do Brasil, com análise de intenção de tratar e seguimento após quatro e oito semanas. A intervenção consistiu na ingestão de cálcio 500mg/dia, cálcio 1500mg/dia e placebo. Os dados foram analisados segundo um modelo generalizado de estimação de equações mistas adotando α 0,05. Resultados O efeito do cálcio em baixa e alta dosagem na evolução ao longo do tempo foi mantido entre os grupos, mesmo após o ajuste para os fatores de confusão. Houve diferença significativa nos parâmetros analisados na interação tempo e grupo (p <0,000) e diminuição nas médias de 12,3mmHg na PAS, 9,2 mmHg na PAD, 3,2 mg/dl creatinina e 7,2 mg/dl proteinúria para o grupo cálcio 500mg/dia. Os resultados foram semelhantes para o grupo com suplementação máxima. Conclusão O cálcio melhorou o prognóstico vascular em mulheres grávidas com hipertensão ao reduzir os níveis pressóricos e os marcadores da pré-eclâmpsia.

Resumen Objetivo Analizar los efectos de los suplementos de calcio en los marcadores de preeclampsia a lo largo del tiempo, comparando el uso de calcio en dosis altas y bajas en mujeres embarazadas con hipertensión. Métodos Se trata de un ensayo clínico aleatorizado con tres grupos paralelos, placebo controlado realizado en consultorios externos de referencia en el control prenatal de alto riesgo en la Región Sur de Brasil, con análisis de intención de tratar y seguimiento luego de cuatro y ocho semanas. La intervención consistió en la ingesta de calcio 500 mg/día, calcio 1500 mg/día y placebo. Los datos se analizaron de acuerdo con un modelo generalizado de estimación de ecuaciones mixtas adoptando α 0,05. Resultados El efecto del calcio en dosis bajas y altas en la evolución a lo largo del tiempo se mantuvo entre los grupos, inclusive después de los ajustes por los factores de confusión. Hubo diferencia significativa en los parámetros analizados en la interacción tiempo y grupo (p <0,000) y reducción de los promedios de 12,3 mmHg en la PAS, 9,2 mmHg en la PAD, 3,2 mg/dl creatinina y 7,2 mg/dl proteinuria en el grupo calcio 500 mg/día. Los resultados fueron parecidos en el grupo con suplemento en dosis máxima. Conclusión El calcio mejoró el pronóstico vascular en mujeres embarazadas con hipertensión al reducir los niveles de presión y los marcadores de preeclampsia. Registro Brasileiro de Ensaios Clínicos: RBR-9ngb95

Abstract Objective To analyze the effects of calcium supplementation on markers of preeclampsia over time by comparing the use of high- and low-dose calcium in hypertensive pregnant women. Methods This is a randomized clinical trial, placebo controlled, with three parallel groups carried out at the reference outpatient clinic for high-risk prenatal care in the South Region of Brazil, with intention-to-treat analysis and follow-up after four and eight weeks. The intervention consisted of ingesting calcium 500mg/day, calcium 1500mg/day and placebo. Data were analyzed according to a generalized mixed equation estimation model adopting α 0.05. Results The effect of low- and high-dose calcium on evolution over time was maintained between groups, even after adjustment for confounding factors. There was a significant difference in the parameters analyzed in the time and group interaction (p <0.000) and a decrease in the means of 12.3 mmHg in SBP, 9.2 mmHg in DBP, 3.2 mg/dl creatinine and 7.2 mg/dl proteinuria for the 500mg calcium/day group. The results were similar for the maximal supplementation group. Conclusion Calcium improved vascular prognosis in hypertensive pregnant women by reducing blood pressure levels and markers of preeclampsia. Brazilian Registry of Clinical Trials: RBR-9ngb95

Impactos da covid-19 sobre a gestaçãono desenvolvimento da pré-eclâmpsia: revisão integrativa / Impacts of COVID-19 during pregnancy on the development of pre-eclampsia: an integrative review

Objetivo: Identificar as evidências cientificas acerca da associação da covid-19 e o desenvolvimento de pré-eclâmpsia. Método: Trata-se de uma revisão integrativa, realizada em abril de 2022, mediante acesso às bases de dados: Medical Literature Analysis and Retrieval System Online (MEDLINE) e Portal Regional da Biblioteca Virtual em Saúde (BVS). A partir da utilização dos descritores em saúde: Gestantes, Pré-eclâmpsia e COVID-19. Resultados: Foram incluídos 15 estudos na síntese avaliativa, onde 13 foram provenientes da PubMed (86,6%) e 02 da BVS (13,3%). Quanto ao desenho, seis (40%) estudos foram do tipo relato ou estudo de caso, cinco (33,3%) do tipo revisão sistemática, com destaque para três revisões com meta-análise, dois (13,3%) se tratou estudos observacionais, um (6,6%) estudo descritivo e um (6,6%) estudo de coorte. Conclusão: Foram identificados estudos que associaram o desenvolvimento da pré-eclâmpsia à infecção causada pelo Covid-19, no entanto, outros estudos destacam a detecção de uma síndrome semelhante a pré-eclâmpsia, destacando a necessidade da realização de um diagnóstico diferencial.(AU)

Objective: To identify the scientific evidence on the association between covid-19 and the development of pre-eclampsia. Method: This is an integrative review, carried out in April 2022, through access to the databases: Medical Literature Analysis and Retrieval System Online (MEDLINE) and Regional Portal of the Virtual Health Library (VHL). Using the health descriptors: Pregnant women, Pre-eclampsia and COVID-19. Results: 15 studies were included in the evaluation synthesis, of which 13 came from PubMed (86.6%) and 02 from the VHL (13.3%). In terms of design, six (40%) studies were of the case report or study type, five (33.3%) were of the systematic review type, with emphasis on three reviews with meta-analysis, two (13.3%) were observational studies, one (6.6%) was a descriptive study and one (6.6%) was a cohort study. Conclusion: Studies were identified that associated the development of pre-eclampsia with infection caused by Covid-19, however, other studies highlight the detection of a syndrome similar to pre-eclampsia, highlighting the need for a differential diagnosis.(AU)

Objetivo: Identificar las evidencias científicas sobre la asociación entre el covid-19 y el desarrollo de preeclampsia. Método: Se trata de una revisión integradora, realizada en abril de 2022, a través del acceso a las bases de datos: Medical Literature Analysis and Retrieval System Online (MEDLINE) y Portal Regional de la Biblioteca Virtual en Salud (BVS). Utilizando los descriptores de salud: Embarazadas, Preeclampsia y COVID-19. Resultados: 15 estudios fueron incluidos en la síntesis de evaluación, de los cuales 13 procedían de PubMed (86,6%) y 2 de la BVS (13,3%). En cuanto al diseño, seis (40%) estudios fueron del tipo informe o estudio de caso, cinco (33,3%) fueron revisiones sistemáticas, especialmente tres revisiones con meta-análisis, dos (13,3%) fueron estudios observacionales, uno (6,6%) fue un estudio descriptivo y uno (6,6%) fue un estudio de cohortes. Conclusión: Fueron identificados estudios que asocian el desarrollo de preeclampsia con infección causada por Covid-19, sin embargo, otros estudios destacan la detección de un síndrome semejante a la preeclampsia, enfatizando la necesidad de realizar un diagnóstico diferencial.(AU)

Gestational hypertension as a factor associated with chronic kidney disease: the importance of obstetric history of women undergoing hemodialysis / Hipertensão gestacional como fator associado à doença renal crônica: a importância do histórico obstétrico de mulheres submetidas à hemodiálise

ABSTRACT Introduction: Pregnancy-related complications may impact women's reproductive cycle and health through their lives. The objective of this study was to evaluate the sociodemographic, clinical, and obstetric history of women undergoing hemodialysis. Methods: We performed a cross-sectional study in a specialized health facility with four hemodialysis units. Sociodemographic characteristics, clinical and personal history, obstetric and perinatal results of women with pregnancies before hemodialysis were evaluated. Prevalence, bivariate, and logistic regression analyses were performed. Results: We included 208 (87.76%) women. Hypertension was the main cause of chronic kidney disease (CKD) (128 women). Rates of adverse perinatal outcomes, including prematurity, low birth weight, miscarriage, fetal death, and neonatal death, were 19.3%, 14.5%, 25.5%, 12.1%, and 5.3%, respectively. Hypertensive syndromes during pregnancy occurred in 37.0% of women, with 12.5% reporting preeclampsia and 1.4% reporting eclampsia. Up to 1 year after birth, 45.2% of women reported hypertension. Hemodialysis due to hypertension was associated with a history of hypertension during pregnancy (OR 2.33, CI 1.27 - 4.24), gestational hypertension (2.41, CI 3.30 - 4.45), and hypertension up to one year after birth (OR 1.98, CI 1.11 - 3.51). Logistic regression showed that gestational hypertension was independently associated with CKD due to hypertension (aOR 2.76, CI 1.45 - 5.24). Conclusion: Women undergoing hemodialysis due to hypertension were more likely to have gestational hypertension or hypertension up to one year after birth. To delay end-stage renal disease, it is necessary to identify women at risk of kidney failure according to their reproductive history.

RESUMO Introdução: Complicações relacionadas à gestação podem afetar o ciclo reprodutivo e a saúde das mulheres ao longo de suas vidas. Este estudo visou avaliar histórico sociodemográfico, clínico e obstétrico de mulheres em hemodiálise. Métodos: Realizamos estudo transversal em unidade de saúde especializada com quatro unidades de hemodiálise. Avaliou-se características sociodemográficas, histórico clínico e pessoal, resultados obstétricos e perinatais de mulheres com gestações anteriores à hemodiálise. Foram realizadas análises de prevalência, bivariadas e regressão logística. Resultados: Incluímos 208 (87,76%) mulheres. Hipertensão foi a principal causa de doença renal crônica (DRC) (128 mulheres). Taxas de desfechos perinatais adversos, incluindo prematuridade, baixo peso ao nascer, aborto espontâneo, óbito fetal e neonatal, foram de 19,3%, 14,5%, 25,5%, 12,1% e 5,3%, respectivamente. Síndromes hipertensivas durante a gestação ocorreram em 37,0% das mulheres, com 12,5% relatando pré-eclâmpsia e 1,4% relatando eclampsia. Até 1 ano após o parto, 45,2% das mulheres relataram hipertensão. Hemodiálise devido à hipertensão foi associada ao histórico de hipertensão na gestação (OR 2,33; IC 1,27 - 4,24), hipertensão gestacional (2,41; IC 3,30 - 4,45), e hipertensão até um ano após o parto (OR 1,98; IC 1,11 - 3,51). A regressão logística mostrou que hipertensão gestacional foi independentemente associada à DRC devido à hipertensão (ORa 2,76; IC 1,45 - 5,24). Conclusão: Mulheres submetidas à hemodiálise por hipertensão foram mais propensas a apresentar hipertensão gestacional ou hipertensão até um ano após o parto. Para retardar a doença renal em estágio terminal, deve-se identificar mulheres em risco de insuficiência renal de acordo com sua história reprodutiva.

Maternal and Perinatal Complications in Eclampsia Patients: Study in a Private Medical College, Dhaka, Bangladesh

Background: Eclampsia is a serious pregnancy complication that can lead to seizures and potentially fatal outcomes for both mother and baby. It is most common in developing countries but improved antenatal care and early intervention have significantly decreased its incidence in developed countries. Risk factors for eclampsia include pre-eclampsia, hypertension, obesity, and renal disease, and early detection and management are crucial for preventing adverse outcomes. Magnesium sulfate is the preferred treatment for seizures, and delivery timing depends on disease severity, gestational age, and fetal well-being. Maternal and perinatal mortality rates vary by country, highlighting the need for continued efforts to improve outcomes for those affected by eclampsia. The study aimed to observe the maternal and perinatal complications in eclampsia patients. Material & Methods: This observational study was conducted at the Department of Gynecology, Gonoshasthaya Nagar Hospital, Dhaka, Bangladesh during the period of January 2020 to June 2020. We included a total of 270 patients with eclampsia who were admitted to a tertiary care hospital. A Purposive consecutive sampling method was followed for the selection of the participants. Results: This study analyzed the demographic and clinical characteristics, maternal and perinatal complications, and risk factors of 270 patients with eclampsia. The majority of patients were aged between 20-34 years (77.8%), and 61.1% were multiparous. Over half of the cases (55.6%) presented with eclampsia between 28-36 weeks of gestation, and 38.9% had a history of preeclampsia in a previous pregnancy. The most common symptoms reported were headaches (88.9%). All cases involved hypertensive disorders, and maternal death was reported in 1.9% of cases. Perinatal complications included low birth weight (44.4%), preterm delivery (36.3%), NICU admission (34.8%), stillbirth (4.4%), and early neonatal death (3.0%). Maternal mortality rates were highest among women aged 20-34 years (56.5%), while perinatal mortality rates were highest among women aged under 20 years (20.0%). The highest maternal mortality rate was observed among women with severe eclampsia (91.4%), and time to treatment was a crucial factor in maternal mortality rates. These findings underscore the need for timely and appropriate care to improve maternal and perinatal outcomes, particularly in high-risk populations. Conclusion: Eclampsia is a serious complication of pregnancy that can result in significant maternal and perinatal morbidity and mortality. Early detection, prompt management, and close monitoring of high-risk pregnancies are crucial in preventing adverse outcomes. Further research is needed to identify effective interventions for preventing and managing eclampsia.

COVID-19 and Preeclampsia: A Systematic Review of Pathophysiological Interactions / COVID-19 e pré-eclâmpsia: uma revisão sistemática de interações fisiopatológicas

Abstract Objective: To review the literature and synthesize evidence on pathophysiological interactions attributed to the simultaneous occurrence of COVID-19 and preeclampsia. Methods: A systematic review was conducted from November (2021) to January (2022) to retrieve observational studies published on the PubMed, LILACS, SciELO Brazil and Google Scholar databases. The search was based on the descriptors [(eclampsia OR preeclampsia) AND (COVID-19)]. Quantitative studies that pointed to pathophysiological interactions were included. Literature reviews, studies with HIV participants, or with clinical approach only were excluded. The selection of studies was standardized and the evaluation was performed by pairs of researchers. Results: In this review, 155 publications were retrieved; 16 met the inclusion criteria. In summary, the physiological expression of angiotensin-converting enzyme-2 (ACE-2) receptors is physiologically increased in pregnant women, especially at the placental site. Studies suggest that the coronavirus binds to ACE-2 to enter the human cell, causing deregulation of the renin-angiotensin-aldosterone system and in the ratio between angiotensin-II and angiotensin-1-7, inducing manifestations suggestive of preeclampsia. Furthermore, the cytokine storm leads to endothelial dysfunction, vasculopathy and thrombus formation, also present in preeclampsia. Conclusion: The studies retrieved in this review suggest that there is a possible overlap of pathophysiological interactions between COVID-19 and preeclampsia, which mainly involve ACE-2 and endothelial dysfunction. Given that preeclampsia courses with progressive clinical and laboratory alterations, a highly quality prenatal care may be able to detect specific clinical and laboratory parameters to differentiate a true preeclampsia superimposed by covid-19, as well as cases with hypertensive manifestations resulting from viral infection.

Resumo Objetivo: Revisar a literatura e sintetizar evidências sobre interações fisiopatológicas atribuídas à ocorrência simultânea de COVID-19 e pré-eclâmpsia. Métodos: Uma revisão sistemática foi conduzida entre novembro (2021) a janeiro (2022) para recuperar estudos observacionais publicados no PubMed, LILACS, SciELO Brasil e Google scholar. A busca foi baseada nos descritores [(eclâmpsia OR pré-eclâmpsia) AND (COVID-19)]. Estudos quantitativos que apontaram interações fisiopatológicas foram incluídos. Estudos de revisão, com participante HIV e apenas com enfoque clínico foram excluídos. A seleção dos estudos foi padronizada com avaliação por duplas de pesquisadores. Resultados: Nesta revisão, 155 publicações foram recuperadas; 16 preencheram os critérios de inclusão. Em síntese, a expressão fisiológica de receptores da enzima conversora da angiotensina-2 (ECA-2) é fisiologicamente potencializada em gestantes, especialmente no sítio placentário. Os estudos sugerem que o coronavírus se liga à ECA-2 para entrar na célula humana, ocasionando desregulação do sistema renina-angiotensina-aldosterona e da razão entre angiotensina-II e angiotensina-1-7, induzindo manifestações sugestivas de pré-eclâmpsia. Ademais, a tempestade de citocinas conduz à disfunção endotelial, vasculopatia e formação de trombos, também presentes na pré-eclâmpsia. Conclusão: Os estudos recuperados nesta revisão sugerem que a superposição de alterações fisiopatológicas entre a COVID-19 e a pré-eclâmpsia envolve, principalmente, a ECA-2 e disfunção endotelial. Tendo em vista que a pré-eclâmpsia cursa com alterações clínicas e laboratoriais progressivas, a atenção pré-natal de qualidade pode ser capaz de detectar parâmetros clínicos e laboratoriais importantes para diferenciar a pré-eclâmpsia verdadeira sobreposta por COVID-19, bem como os casos que mimetizam a doença hipertensiva consequente à infecção viral.

Factores de riesgo predisponentes al desarrollo de preeclampsia y eclampsia en el embarazo / Risk factors for the development of preeclampsia and eclampsia in pregnancy

Resumen La preeclampsia es una patología de origen desconocido, de alta incidencia en la salud materna y neonatal. Caracterizada como una hipertensión gestacional grave multisistémica a partir de las 20 semanas de gestación hasta el parto y posparto, siendo de los trastornos más prevalentes en el mundo y la principal causa de muerte materna en Ecuador durante 2022. El objetivo fue realizar una revisión bibliográfica respecto de los factores de riesgo que predisponen preeclampsia en embarazadas. Mediante una revisión bibliográfica de estudios correspondientes a factores predisponentes al desarrollo de preeclampsia y eclampsia en embarazadas cuyos resultados se enfocaron a pacientes adultas diagnosticadas con dichas patologías mediante estrategia PICO, aplicando criterios de inclusión y exclusión. La preeclampsia conlleva una diversidad de factores de riesgo familiares patológicos como preeclampsia previa, hipertensión o enfermedades renales, diabéticas y obesidad; otros factores incluyen: edad, raza, embarazos gemelares, multiparidad, progenitores de distinta índole. Los factores significativos para presentar la enfermedad fueron en su mayoría factores ginecoobstétricos donde destacaron multiparidad, edad, obesidad, malnutrición, hipertensión previa y factores hereditarios.

Abstract Preeclampsia is a condition of unknown origin, with a high incidence in maternal and neonatal health, characterized as a severe multisystemic gestational hypertension from the 20th week of gestation until childbirth and postpartum. Among the most prevalent disorders worldwide, in Ecuador was the main cause of maternal death during 2022. The objective was to conduct a literature review regarding risk factors that predispose pregnant women to preeclampsia. Through a literature review of studies corresponding to predisposing factors for the development of preeclampsia and eclampsia in pregnant women, whose results were focused on adult patients diagnosed with said pathologies through the PICO strategy, applying inclusion and exclusion criteria. Preeclampsia involves a variety of pathological familial risk factors such as prior preeclampsia, hypertension, renal diseases, diabetes, and obesity; other factors include age, race, twin pregnancies, multiparity, and diverse parental lineage. The significant factors for presenting the disease were mostly gynecobstetric factors, prominently multiparity, age, obesity, malnutrition, prior hypertension, and hereditary factors.

MR Imaging in Eclampsia

Background : The aim of this study is to determine the distribution and nature of Cranial MRI findings in eclamptic patients, and to correlate them with clinical and laboratory data. Materials and Methods : This study was conducted in the Department of Obstetrics and Gynecology in Sri Ramachandra Institute of Higher Education and Research. A total number of 35 Eclamptic patients were included in this study and they were analyzed retrospectively. Laboratory parameters, Blood Pressure and Cranial MRI was performed for all and the same were analyzed statistically. Results : Out of 35 Eclamptic patients, MR Imaging was normal in 6 patients. Among the 29 patients with abnormal MRI, Cortical-subcortical Lesion, appeared iso/hypo-intense in T-1 weighted images and hyper intense in T-2 weighted images. In most of the patients, occipital lobe was involved followed by involvement of other lobes such as Parietal, Frontal, Temporal, Basal Ganglia and Cerebellum. When patients with and without positive MRI findings were compared regarding clinical features such as Headache, Blurred Vision, Nausea and Vomiting, Epigastric Pain, Loss of Consciousness, Reduced Urine Output there was no statistically significant difference between the two groups. Similarly, there was no statistical difference in mean arterial pressures between MRI positive and MRI negative patients (p=0.218) however, it was found that those with MR imaging positive features had a higher Blood Pressure than those with MRI negative findings. Among the laboratory parameters, in the patients with abnormal MRI findings Fibrinogen was found to be significantly low than those with normal MRI findings (p=0.0002).

Placental expression of striatin & endothelial nitric oxide synthase in women with & without pre-eclampsia

Background & objectives: Striatin is a multi-domain scaffolding protein essential for activating endothelial nitric oxide synthase (eNOS). However, its role in pre-eclampsia remains use explored. Hence, this study aimed to investigate the association between striatin and eNOS in regulating nitric oxide (NO) production in the placenta of women with and without pre-eclampsia. Methods: Forty pregnant women each without (controls) and with pre-eclampsia (cases) were enrolled in the study. Blood striatin and NO concentrations were detected by the ELISA. Protein expression of striatin, phosphorylated eNOS (peNOS), inducible NOS (iNOS) and phosphorylated NF-?B were measured in the placental tissues by Western blot. Twenty four hour urinary protein and serum urea, uric acid and creatinine were analyzed as an autoanalyzer. Placental histology was analyzed by haematoxylin and eosin staining. Results: Compared to normotensive pregnant women, the levels of serum NO and striatin were decreased in pre-eclamptic women. The protein expression of striatin and peNOS was significantly reduced (P<0.05) while p65NF-?B and iNOS were upregulated considerably (P<0.05) in the placenta of cases compared to controls. Interpretation & conclusions: Our results show for the first time that decreased striatin expression was associated with decreased peNOS protein expression in the placental tissue of pre-eclamptic women. Interestingly, no significant difference was found in blood striatin or NO levels between controls and cases. Thus, therapies that improve placental striatin expression are attractive possibilities, both for prevention as well as treatment of endothelial dysfunction in pre-eclampsia.

Prediction of pre-eclampsia in diabetic pregnant women

Background & objectives: Gestational or preexisting diabetes is one of the risk factors of pre-eclampsia. Both are responsible for higher maternal and fetal complications. The objective was to study clinical risk factors of pre-eclampsia and biochemical markers in early pregnancy of women with diabetes mellitus (DM)/gestational diabetes mellitus (GDM) for the development of pre-eclampsia. Methods: The study group comprised pregnant women diagnosed with GDM before the 20 wk of gestation and DM before pregnancy and the control group had age-, parity- and period of gestation-matched healthy women. Sex hormone-binding globulin (SHBG), insulin-like growth factor-I (IGF-I) and 25-hydroxy vitamin D [25(OH)D] levels and the polymorphism of these genes was evaluated at recruitment. Results: Out of 2050 pregnant women, 316 (15.41%) women (296 had GDM and 20 DM before pregnancy) were included in the study group. Of these, 96 women (30.38%) in the study group and 44 (13.92%) controls developed pre-eclampsia. Multivariate logistic regression analysis indicated those who belonged to the upper middle and upper class of socio-economic status (SES) were likely to be at 4.50 and 6.10 times higher risk of developing pre-eclampsia. The risk of getting pre-eclampsia among those who had DM before pregnancy and pre-eclampsia in their previous pregnancy was about 2.34 and 4.56 times higher compared to those who had no such events, respectively. The serum biomarkers [SHBG, IGF-I and 25(OH)D] were not found to be useful in predicting pre-eclampsia in women with GDM. To predict risk of development of pre-eclampsia, the fitted risk model by backward elimination procedure was used to calculate a risk score for each patient. Receiver operating characteristic (ROC) curve for pre-eclampsia showed that area under the curve was 0.68 (95% confidence interval: 0.63-0.73); P<0.001. Interpretation & conclusions: The findings of this study suggested that pregnant women with diabetes were at a higher risk for pre-eclampsia. SES, history of pre-eclampsia in previous pregnancy and pre-GDM were found to be the risk factors.

Definición de la presión arterial normal a las 11-14 semanas de gestación según riesgo / Definition of normal blood pressure at 11 to 14 weeks' gestation according to risk

Resumen Objetivo: Definir la presión arterial normal en el primer trimestre de la gestación según el desempeño para predecir preeclampsia. Método: Estudio de cohorte en embarazos de feto único, según el modelo de riesgos en competencia para preeclampsia. La presión arterial se midió de manera estandarizada entre las 11 y 14 semanas de gestación. Resultados: En 797 embarazos incluidos hubo 40 (5.0%, intervalo de confianza del 95% [IC 95%]: 3.6-6.4) partos con preeclampsia. Las presiones arteriales sistólica, diastólica y media fueron respectivamente de 101 (9), 68 (8) y 79 (8) mmHg en las embarazadas que no desarrollaron preeclampsia, frente a 109 (10), 75 (8) y 86 (8) mmHg en las que sí (p < 0.001, prueba t de Student). Las áreas bajo la curva fueron 0.707 (0.637-0.777), 0.728 (0.661-0.795) y 0.738 (0.673-0.803). A 3% de falsos positivos, los puntos de corte fueron 119, 83 y 94 mmHg con valores predictivos negativos del 95.6%. Conclusiones: Es factible definir normalidad para la presión arterial en el embarazo con base bioestadística y clínica.

Abstract Objective: To define normal blood pressure at first trimester of pregnancy by performance for pre-eclampsia prediction. Method: A cohort study in singleton pregnancies, according to the competing risks model for pre-eclampsia. Blood pressure was measured according to a standardized method at 11 to 14 weeks' gestation. Results: Among 797 pregnancies included, there were 40 (5.0%, IC95 3.6; 6.4) deliveries with pre-eclampsia. The systolic, diastolic, and mean arterial blood pressures were respectively of 101(9), 68(8) and 79(8) mmHg in pregnant women who did not develop pre-eclampsia, against 109(10), 75(8) and 86(8) in those who did (p < 0.001, t-test). The areas under the curves were 0.707 (0.637; 0.777), 0.728 (0.661; 0.795), and 0.738 (0.673; 0.803). At a 3% of false positive rate, the cut-off points were 119, 83 and 94 mmHg with predictive values of negative of 95.6%. Conclusions: It is feasible to define the normal values for blood pressure in pregnancy on biostatistic and clinical basis.

Exposição ao cádmio e Síndromes Hipertensivas da Gestação: uma revisão sistemática / Cadmium exposure and Hypertensive Disorders of Pregnancy: a systematic review

RESUMO As Síndromes Hipertensivas da Gestação (SHG) são uma das principais causas de morbimortalidade materna. Evidências crescentes indicam a associação entre a exposição ao cádmio e a hipertensão arterial na população em geral, mas não as SHG. Afim de investigar esse tema, realizou-se uma revisão sistemática seguindo as diretrizes PRISMA, nas bases de dados BVS/Lilacs, PubMed/Medline e SciELO e no repositório da Universidade de São Paulo (USP) até agosto de 2021. A qualidade metodológica foi avaliada pelo checklist Downs and Black. Selecionaram-se dezenove artigos, sendo treze caso-controle, quatro coortes e dois seccionais. No total, 11.451 participantes foram avaliadas, sendo 1.445 (12,6%) com SHG e, destas, 1.071 (74,1%) com pré-eclâmpsia. Observou-se o ajuste inadequado para confundimento em onze estudos. Dos sete estudos considerados de boa qualidade metodológica, quatro relataram associação positiva e três não a observaram, enquanto somente um estudo observou diferença de média, que foi maior nas gestantes com SHG. Atribuiu-se a divergência dos resultados às diferenças metodológicas e ao ajuste inadequado para os fatores de confusão. Como o cádmio é um metal tóxico que pode levar ao aumento do estresse oxidativo, que desempenha papel importante na fisiopatologia das SHG, estudos adicionais são necessários para elucidar esta associação.

ABSTRACT Hypertensive Disorders of Pregnancy (HDP) are one of the main causes of maternal morbimortality. Strong evidence point to an association between cadmium and hypertension in the general population, but not HDP. A systematic review was carried out to investigate this potential relationship, following PRISMA guidelines, in the BVS/LILACS, PubMed/MEDLINE, and SciELO databases and a repository (University of São Paulo - USP) until August 2021. The methodological quality was assessed using the Downs and Black checklist. Nineteen articles were selected, thirteen of which were case-control, four were cohorts, and two were cross-sectional. A total of 11.451 participants were evaluated, 1.445 (12.6%) with HDP, and of these 1.071 (74.1%) with preeclampsia. The inadequate adjustment for confounding was observed in eleven studies. Out of the seven studies considered good methodological quality, four reported a positive association, and three did not observe it. In contrast, only one observed a mean difference, which was higher in HDP. The inconsistency of the results was attributed to the methodological differences and inadequate adjustment for confounding. As cadmium is a toxic metal that can induce an increase in oxidative stress, which plays an essential role in the pathophysiology of HDP, additional studies are needed to elucidate this association.