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.

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.

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

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.

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.

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.

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.

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.

Evaluation of first- and third-trimester afamin levels in preeclampsia

SUMMARY OBJECTIVE: The aim of this study was to investigate serum afamin levels in the first and third trimesters in preeclampsia. METHODS: Serum samples from 118 patients in the first and third trimesters were analyzed. Serum samples were collected from pregnant women who had enrolled in the first trimester. Blood was then collected from pregnant women who had developed preeclampsia and from healthy controls in the third trimester. The collected blood samples were resolved for analysis, and serum afamin concentrations were measured in the first and third trimesters. Preeclampsia and healthy controls were compared. RESULTS: There was no significant difference between the control and preeclampsia groups in terms of age, body mass index, and smoking. Afamin levels in the first and third trimesters were higher in the preeclampsia group than in the control group (p<0.05). In the subgroup analysis of the preeclampsia group, afamin levels were higher in the early-onset preeclampsia group than in the late-onset preeclampsia group in the first and third trimesters (p<0.05). In the receiver operating characteristic analysis afamin levels were 96.23 ng/mL in the first trimester and 123.57 ng/mL in the third trimester as cut-off values for preeclampsia. CONCLUSION: Serum afamin levels are useful for predicting preeclampsia in the first trimester in pregnant women and can be used in clinical practice as a supportive biomarker for the diagnosis of preeclampsia in the third trimester. Meta-analyzes are needed to investigate the effect of afamin levels in the prediction and diagnosis of preeclampsia and to determine the cut-off value.

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.

Ultrassonografia morfológica de primeiro trimestre: importante ferramenta para rastreio de aneuploidias e pré-eclâmpsia / First-trimester morphological ultrasound: important tool for aneuploidy and pre-eclampsia screening

No início do século 20, as altas taxas de mortalidade materna e infantil estimularam o desenvolvimento de um modelo de atendimento pré-natal que mantivesse características parecidas até os dias atuais. Nesse modelo, haveria maior concentração de visitas durante o final do terceiro trimestre de gestação, devido às maiores taxas de complicações nas fases finais da gestação e à dificuldade de prever a ocorrência de resultados adversos durante o primeiro trimestre. Atualmente, a avaliação clínica durante o primeiro trimestre, com auxílio da ultrassonografia e marcadores bioquímicos, pode prever uma série de complicações que acometem a gestação, incluindo cromossomopatias, pré-eclâmpsia, restrição de crescimento fetal, anomalias fetais e trabalho de parto pré-termo.

At the beginning of the 20th century, the high rates of maternal and infant mortality stimulated the development of a model of prenatal care that maintained similar characteristics until the present day. In this model, there would be a greater concentration of visits during the end of the third trimester of pregnancy, due to the higher rates of complications in the final stages of pregnancy and the difficulty in predicting the occurrence of adverse outcomes during the first trimester. Currently, clinical evaluation during the first trimester, with the aid of ultrasound and biochemical markers, can predict a series of complications that affect pregnancy, including chromosomal disorders, preeclampsia, fetal growth restriction, fetal anomalies and preterm labor.

MATERNAL NEAR MISS: AN INDIAN TERTIARY CARE CENTRE AUDIT

BACKGROUND: Despite advances in medical sciences and increased awareness of measures for safe child birth, unacceptably high maternal morbidity and mortality continues in developing countries like India. Ours being a tertiary care centre, draws a lot number of high risk pregnancies and referrals. By auditing the near miss cases2 i.e., a critically ill pregnant or recently delivered woman who was on the verge of death but survived a problem during pregnancy, childbirth, or within 42 days of the pregnancy's termination, we aim to identify the causes, factors leading to near miss2 and the management given to near miss2 and maternal deaths. The AIMS AND OBJECTIVES: present study aims to determine the magnitude, as well as to identify the pattern of Maternal Near Miss2 (MNM), at Siddhartha Medical College, Vijayawada, during the study period of two years. To anal OBJECTIVES: yse 1)Adverse events leading to a maternal near-miss2, 2) Disorders underlying these cases, 3)Sociodemographic factors and 4)Contributing factors A hospital based retros METHODOLOGY: pective observational study to assess the frequency and nature of maternal near miss2 events among the obstetric cases managed at Siddhartha Medical College, Vijayawada over a period of two years. The followi RESULTS: ng are the major causes identified leading to maternal near miss2 during our study Severe Eclampsia 17%, Post-partum Haemorrhage 17%, Pulmonary Edema due to severe pre eclampsia3 9%, Antepartum Eclampsia 9%, HELLP 9%, Ruptured ectopic pregnancy 7%, Cardiac failure 7%, Postpartum Eclampsia 7%, Imminent Eclampsia 4%, Abruption 4%, Rupture uterus 2%. In our study Maternal near miss2 ratio incidence: 0.0254, Severe maternal outcomes ratio : 3, Maternal near miss2 to mortality ratio: 0.433 CONCLUSION: We observed in majority of the cases level 1 and level 2 delays in reporting to our institution

Manejo da hipertensão gestacional no pré-natal: validação de cenário para a simulação clínica / Manejo de hipertensión gestacional: validación de un escenario de simulación clínica / Management of gestational hypertension: Validation of a clinical simulation scenario

Objetivo: desenvolver e validar um cenário e checklist avaliativo para a simulação clínica no ensino em enfermagem, cujo tema é atuação do enfermeiro ante a hipertensão gestacional durante o pré-natal. Materiais e método: trata-se de estudo metodológico, desenvolvido entre janeiro e julho de 2019, seguindo as etapas: overview, scenario, scenario design progression, debriefing e assessment. Participaram do estudo 11 voluntários (4 atores, 2 alunos e 5 juízes). Para a validação, procedeu-se à apresentação do cenário aos juízes como atividade de ensino, com todas as etapas, e, para a análise dos dados obtidos, realizou-se o cálculo do índice de validação de conteúdo (IVC) a partir de respostas dos juízes em uma escala Likert, que avaliou 20 itens sobre o cenário e o checklist. Resultados: classifica-se o cenário validado como de alta fidelidade e de baixa complexidade, e se propõe uma situação em que uma gestante apresentando pressão arterial limítrofe comparece a uma consulta de pré-natal com o enfermeiro. Objetiva-se avaliar se o estudante conhece os critérios diagnósticos da hipertensão gestacional e o manejo adequa-do da situação. O checklist validado se estrutura em três eixos: postura, conhecimento/raciocínio clínico e orientações. Contém destaques nas ações consideradas prioritárias de serem executadas no cenário. O IVC obtido foi de 0,89. Conclusões: o cenário elaborado foi validado pelos juízes. Espera-se que esta seja mais uma ferramenta educacional disponível para o ensino de enfermagem por meio da simulação clínica. Destaca-se que a simulação clínica propõe o ensino centrado no estudante e vem sendo amplamente utilizada na graduação em enfermagem no Brasil e no mundo.

Objetivo: desarrollar y validar un escenario y una lista de verificación para evaluar la simulación clínica en la educación de enfermería, cuyo tema es la actuación de los profesionales de enfermería frente a la hipertensión gestacional durante la atención prenatal. Materiales y método: estudio metodológico desarrollado entre enero y julio de 2019 siguiendo los pasos: resumen, escenario, progresión del diseño del escena-rio, debriefing y evaluación. Once voluntarios (4 actores, 2 estudiantes y 5 jueces) participaron del estudio. Para la validación, se presentó el escenario ante los jueces como una actividad didáctica, con todas las etapas involucradas. Para el análisis de los datos obtenidos, se calculó el índice de validación de contenido (IVC) a partir de las respuestas de los jueces, empleando una escala tipo Likert que evaluó 20 ítems sobre el escenario y lista de verificación. Resultados: el escenario validado se clasifica como de alta confiabilidad y baja complejidad, proponiendo una situación en la que una mujer embarazada asiste a una consulta prenatal con un profesional de enfermería reportando presión arterial limítrofe. El objetivo es evaluar si el estudiante conoce los criterios diagnósticos de hipertensión gestacional y el manejo adecuado de la situación. Por su parte, la lista de verificación validada se estructura en torno a tres ejes: postura, conocimiento/razonamiento clínico y pautas, los cuales señalan las acciones consideradas prioritarias ante el escenario planteado. El IVC obtenido fue de 0,89. Conclusión: el escenario propuesto fue validado, por lo que es de esperar que se constituya en una herramienta disponible para la enseñanza de enfermería a través de la simulación clínica. Se destaca que la simulación clínica propone un enfoque de enseñanza centrado en el estudiante y ha sido ampliamente utilizada en la formación en enfermería a nivel de pregrado en Brasil y en el mundo.

Objective: To develop and validate a scenario and an evaluative checklist for the clinical simulation of the role of nurses in the face of gestational hypertension during prenatal care in nursing education. Materials and method: Methodological study conducted between January and July 2019, following the steps: overview, scenario, scenario design progression, debriefing and assessment. Eleven volunteers (4 actors, 2 students and 5 judges) participated in the study. For validation, the scenario was presented as a teaching activity to selected judge experts, with all the embedded steps involved. Data analysis involved the calculation of the content validation index (CVI) based on the responses by judges, using a Likert scale that evaluated 20 items about the scenario and the checklist. Results: The validated scenario is classified as of high-reliability and low-complexity, proposing a situation in which a pregnant woman attends a prenatal consultation reporting borderline blood pressure to the nursing professional. The objective of this exercise is to assess whether a student knows the diagnostic criteria for gestational hypertension and the appropriate management for this situation. The validated checklist is structured around three axes: posture, knowledge/clinical reasoning, and guidelines, which contain highlights on prioritized actions to be deployed in the face of such a scenario. The CVI obtained was 0.89. Conclusion: The scenario elaborated was validated by the judges. Hence, we expect this becomes another educational tool for nursing education through clinical simulation. It is noteworthy that clinical simulation proposes a student-centered teaching approach that has been widely used in undergraduate nursing education in Brazil and worldwide.

Pregnancy-Induced Hypertension - Ayurvedic Understanding

Pregnancy-induced hypertensive disorders are included among the most common medical complications of pregnancy with an incidence of 5–10%. Hypertension that develops as a direct result of gravid state is referred to as ‘pregnancy-induced hypertension’. The timely management of pregnancy complicated with hypertensive disorders is significant, otherwise it can lead to adverse fetal, neonatal and maternal outcomes. The basic pathology in pre-eclampsia, one of the types of hypertensive disorders is endothelial dysfunction and intense vasospasm due to abnormal placentation compromising blood flow to the foetoplacental unit. There is no direct reference of pregnancy-induced hypertension in Ayurveda classics, but the manifested symptoms can be explained within the purview of Ayurveda. Abnormality in placentation can be considered as impairment in the normal functioning of Vata dosha and when the pathology progresses further; Kapha, Pitta also play their own roles. In a woman with or without a previous history of pre-eclampsia, intervention should begin from pre-conceptional period. Planned pregnancy after pre-conceptional care followed by Garbhini paricharya along with the use of Garbhasthapaka dravya, Rasayana dravya, Masanumasika Garbhasravahara dravya can play significant roles in the prevention as well as management of pregnancy-induced hypertension thus improving the maternal and foetal outcomes.

Diagnóstico y manejo en primer nivel de atención de preeclampsia posparto de inicio tardío. Reporte de caso / Diagnosis and management of late-onset postpartum preeclampsia at the first level of care. Case report

Introducción: La hipertensión postparto de inicio tardío se presenta desde las 48 horas hasta las 6 semanas postparto, afectando al 2% de los embarazos relacionados o no con antecedentes de hipertensión gestacional. La preeclampsia posparto tiene una incidencia del 5,7% a las 72 horas del parto y está asociada a varios factores maternos como la edad (≥ 35 años), etnia (negra) y obesidad (IMC ≥ 30), presentando mayor riesgo en embarazos múltiples, madres añosas (mayores de 35 años) hogares con bajos ingresos económicos. Los síntomas más frecuentes de esta patología son cefalea, disnea, trastornos visuales y edema periférico.Objetivo: Describir la experiencia en un centro de salud de atención primaria, el manejo de una paciente diagnosticada de preeclampsia posparto de inicio tardío, así como las caracte-rísticas clínicas y factores de riesgo.Presentación del caso: Se presenta el caso de una paciente indígena de 32 años con antece-dente de parto gemelar quien en su control del puerperio a las 72 horas presentó hipertensión arterial, cefalea frontal, edema periférico y proteinuria estableciéndose el diagnóstico de pree-clampsia posparto de inicio tardío. No fue posible la referencia a un segundo nivel de atención por las características culturales de la paciente por lo cual recibió manejo clínico y tratamiento en el primer nivel de atención presentando una evolución favorable sin complicaciones. Conclusiones y recomendaciones: La hipertensión posparto de inicio tardío es una patolo-gía poco frecuente en el puerperio, infradiagnosticada, con complicaciones cardiovasculares a corto y largo plazo, por lo cual su diagnóstico, diferenciación y manejo debe ser óptimo en base a las recomendaciones existentes.

Introduction: Late-onset postpartum hypertension occurs from 48 hours to 6 weeks pos-tpartum, affecting 2% of pregnancies related or not to a history of gestational hypertension. Postpartum preeclampsia has an incidence of 5.7% at 72 hours postpartum and is associa-ted with several maternal factors such as age (≥ 35 years), ethnicity (black) and obesity (BMI ≥ 30), presenting higher risk in multiple pregnancies, elderly mothers (older than 35 years) low-income households. The most frequent symptoms of this pathology are headache, dysp-nea, visual disturbances and peripheral edema.Objective: To describe the experience in a primary care health center, the management of a patient diagnosed with late-onset postpartum preeclampsia, as well as the clinical characte-ristics and risk factors.Case presentation: We present the case of a 32-year-old indigenous patient with a history of twin birth who in her puerperium control at 72 hours presented arterial hypertension, frontal headache, peripheral edema and proteinuria establishing the diagnosis of late-onset pos-tpartum preeclampsia, after which treatment was initiated at the first level of care, making referral difficult due to cultural characteristics. Conclusions and recomendations: Late-onset postpartum hypertension is an infrequent pathology in the puerperium, underdiagnosed, with short and long-term cardiovascular com-plications, so its diagnosis, differentiation and management should be optimal based on existing recommendations