How can we reduce maternal mortality due to preeclampsia? The 4P rule.

In low and middle-income countries such as Brazil, most maternal deaths are related to hypertensive complications. Preeclampsia is the leading cause of maternal mortality and morbidity. Significant proportion is associated with the following factors: lack of identification of high-risk women, lack of adequate prevention, difficulty in maintaining a high-risk prenatal follow-up, delayed diagnosis, insecurity and low use of magnesium sulphate, delayed pregnancy interruption and lack of postpartum follow-up of these high-risk cases. Four major actions are proposed to minimize this alarming clinical picture and reduce the mortality rates due to preeclampsia, called the "4 P Rule" (Adequate Prevention - Vigilant Prenatal Care - Timely Delivery (Parturition) - Safe Postpartum). From this simple "rule" we can open a range of important processes and reminders that may help in the guidance of preeclampsia management.

Synthesis of evidence for managing hypertensive disorders of pregnancy in low middle-income countries: a scoping review.

BACKGROUND AND OBJECTIVES: Hypertensive disorders of pregnancy (HDPs) remain one of the leading causes of maternal mortality globally, especially in Low- and middle-income countries (LMICs). To reduce the burden of associated morbidity and mortality, standardized prompt recognition, evaluation, and treatment have been proposed. Health disparities, barriers to access to healthcare, and shortage of resources influence these conditions. We aimed to synthesize the literature evidence for the management of HDPs in LMICs. METHODS: A scoping review was conducted in five databases (PubMed, Web of Science, Epistemonikos, Clinical Key and, Scielo) using MeSh terms, keywords, and Boolean connectors. We summarized the included studies according to the following categories: study design, objectives, settings, participant characteristics, eligibility criteria, interventions, assessed outcomes, and general findings. RESULTS: Six hundred fifty-one articles were retrieved from the literature search in five databases. Following the selection process, 65 articles met the predefined eligibility criteria. After performing a full-text analysis, 27 articles were included. Three themes were identified from the articles reviewed: prevention of HDPs, management of HDPs (antihypertensive and non-hypertensive management) and pregnancy monitoring and follow-up. The topics were approached from the perspective of LMICs. CONCLUSIONS: LMICs face substantial limitations and obstacles in the comprehensive management of HDPs. While management recommendations in most LMICs align with international guidelines, several factors, including limited access to crucial medications, unavailability of diagnostic tests, deficiencies in high-quality healthcare infrastructure, restrictions on continuing professional development, a shortage of trained personnel, community perceptions of preeclampsia, and outdated local clinical practice guidelines, impede the comprehensive management of patients. The development and implementation of protocols, standardized guides and intervention packages are a priority.

Time in therapeutic range and risk of preeclampsia in chronic hypertensive pregnant women.

Pregnancy Hypertensive Disorders (PHD), particularly Preeclampsia (PE), are significant contributors to maternal-fetal morbidity and mortality, with chronic arterial hypertension (CH) being a major risk factor. The prevalence of CH has risen alongside obesity and advanced maternal age. While antihypertensive treatment mitigates adverse pregnancy outcomes, the duration of effective blood pressure (BP) control, termed Time in Therapeutic Range (TTR), has not been extensively studied in pregnant women. TTR, reflecting the proportion of time BP remains within target ranges, predicts long-term cardiovascular and renal events in the general population but remains unexplored in pregnancy. This study investigates the association between TTR, assessed through office BP (OBP) and ambulatory BP monitoring (ABPM), and PE development in pregnant women with CH. In a retrospective longitudinal study, data from 166 pregnant women with HA referred to our hospital analyzed. BP was measured using OBP and ABPM from 10 weeks of gestation, with TTR calculated as the percentage of visits where BP remained within target ranges. The study defined four TTR control groups: 0%, 33%, 50-66%, and 100%. Results showed that 28% of the participants developed PE, with a higher incidence correlating with lower TTR in ABPM. TTR in ABPM was a significant predictor of PE risk, with the best-controlled group (100% TTR) demonstrating a 92% reduced risk compared to those with 0% TTR. The agreement between OBP and ABPM TTR was low, emphasizing the importance of ABPM for accurate BP monitoring in pregnancy. This study indicates that integrating ABPM for TTR assessment in high-risk pregnancies has the potential to reduce maternal and fetal complications.

The Nitrate-Nitrite-Nitric Oxide Pathway: Potential Role in Mitigating Oxidative Stress in Hypertensive Disorders of Pregnancy.

Hypertensive diseases of pregnancy (HDPs) represent a global clinical challenge, affecting 5-10% of women and leading to complications for both maternal well-being and fetal development. At the heart of these complications is endothelial dysfunction, with oxidative stress emerging as a pivotal causative factor. The reduction in nitric oxide (NO) bioavailability is a vital indicator of this dysfunction, culminating in blood pressure dysregulation. In the therapeutic context, although antihypertensive medications are commonly used, they come with inherent concerns related to maternal-fetal safety, and a percentage of women do not respond to these therapies. Therefore, alternative strategies that directly address the pathophysiology of HDPs are required. This article focuses on the potential of the nitrate-nitrite-NO pathway, abundantly present in dark leafy greens and beetroot, as an alternative approach to treating HDPs. The objective of this review is to discuss the prospective antioxidant role of nitrate. We hope our discussion paves the way for using nitrate to improve endothelial dysfunction and control oxidative stress, offering a potential therapy for managing HDPs.

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

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.

Complicaciones maternas y embarazo adolescente en América Latina: Revisión sistemática y metaanálisis / Maternal complications and adolescent pregnancy in Latin America: A systematic review and meta-analysis

RESUMEN Objetivo: Evaluar el riesgo de complicaciones maternas en el embarazo adolescente en Latinoamérica y El Caribe durante el periodo 2012 al 2021. Métodos: Se realizó una búsqueda sistemática en 6 bases de datos: PubMed, SCOPUS, Web Of Science, EMBase, LILACS y Scielo. Los artículos incluidos fueron procedentes de paises de Latinoamérica y contaron con cualquiera de las siguientes variables: preeclampsia, eclampsia, hemorragia puerperal y sepsis puerperal publicados desde el 2012 al 2021 y que compararan adolescentes y adultas embarazadas. Se excluyeron artículos que no presentaron hallazgos separados de Latinoamérica y/o El Caribe, que no se encontraban disponibles la versión completa y que estaban enfocados en pacientes con alguna enfermedad en específico. Para el riesgo de sesgo se empleó la Escala de Newcasttle-Ottawa para estudios de casos y controles. La medida de resumen empleada fue el Odds Ratio con un intervalo de confianza al 95% para cada estudio. Resultados: Se incluyeron 4 estudios. No se evidenció el riesgo de preeclampsia en adolescentes embarazadas (OR = 0.93, IC 95% 0.69 - 1.25) ni hemorragia puerperal (OR = 0.86, IC 95% 0.74 - 0.99). Por otro lado, se mostró el riesgo de eclampsia (OR = 2.43, IC 95% 1.29 - 4.58) en adolescentes embarazadas, pero con alta heterogeneidad entre los estudios (I2 = 76%). Conclusiones: Se evidenció un riesgo de eclampsia en adolescentes embarazadas, pero no en preeclampsia ni hemorragia puerperal; sin embargo, estos resultados deben de tomarse con cautela. Registro de protocolo: CRD42021286725 (PROSPERO)

ABSTRACT Objective: To assess whether maternal complications are a risk in adolescent pregnancy in Latin America and the Caribbean during the period 2012 to 2021. Methods: A systematic search was carried out in 6 databases: PubMed, SCOPUS, Web of Science, EMBase, LILACS and Scielo. The articles included were from Latin American countries and had any of the following variables: preeclampsia, eclampsia, puerperal hemorrhage and puerperal sepsis published from 2012 to 2021 and comparing pregnant adolescents and adults. Articles that did not present separate findings from Latin America and/or the Caribbean, that the full version was not available, and that were focused on patients with a specific disease were excluded. For risk of bias, the Newcastle-Ottawa Scale Case-Control Studies was used. The summary measure used was the Odds Ratio with a 95% confidence interval for each study. Results: 4 studies were included. The risk of preeclampsia in pregnant adolescents and postpartum hemorrhage (OR = 0.86, 95% CI 0.74 - 0.99) were not evidenced (OR = 0.93, 95% CI 0.69 - 1.25). On the other hand, the risk of eclampsia (OR = 2.43, 95% CI 1.29 - 4.58) in pregnant adolescents was shown, but with high heterogeneity between studies (I2 = 76%). Conclusions: A risk of eclampsia was evidenced in pregnant adolescents, but not in preeclampsia nor postpartum hemorrhage. However, these results should be taken with caution. Protocol record: CRD42021286725 (PROSPERO)

Prevención de la preeclampsia y su relevancia en el contexto latinoamericano: una revisión narrativa / Prevention of preeclampsia and its relevance in the Latin American context: a narrative review

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.

Prevención de la preeclampsia: desde la dieta hasta la aspirina: revisión de la literatura / Prevention of preeclampsia: from diet to aspirin: review of the literature

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.

Effects of calcium supplementation on changes in the IL2, IL4, IL6, IL10 axes and oxidative stress in pregnant women at risk for pre-eclampsia.

BACKGROUND: Pregnant women with hypertensive disorders are at increased risk for inflammatory diseases and oxidative stress. The dilemma raised by the best dosage of calcium supplementation on these factors is evident. The aim of the current study was to examine the effects of calcium on biomarkers of the purinergic system, inflammation and oxidative stress, which are factors contributing to vascular damage in pregnant women at high risk of pre-eclampsia. METHODS: A prospective, double-blind and placebo-controlled study conducted with 101 women at risk of pre-eclampsia were randomized to take 500 mg calcium/day or 1,500 mg calcium/day or placebo for 6 weeks from the 20th gestational week until delivery. Fasting blood samples were collected at the beginning of the study and 6 weeks after the intervention. RESULTS: Taking calcium supplements (500 mg calcium/day) led to a significant increase in ATP hydrolysis (p < 0.05), NTPDase activity with increased hydrolysis of ADP and AMP nucleotides in platelets and lymphocytes. In the intragroup analysis IL-2, IL-6, IL-4 and interferon-É£ presented lower values in the calcium 1,500 mg/day group (p < 0.005). Oxidative stress was assessed by TBARS pro-oxidant marker, with an increase for the calcium groups when compared to the placebo group. The Vitamin C antioxidant marker presented a significant increase (p < 0.005) for the group that received high calcium doses. CONCLUSIONS: Calcium administration for 6 weeks had antioxidant action and positively modulated the purinergic system and inflammatory markers in pregnant women at risk of pre-eclampsia.

Subphenotypes of severe early-onset pre-eclampsia at hospital admission. A Latin American single-center exploratory latent class analysis.

OBJECTIVES: To identify distinct subphenotypes of severe early-onset pre-eclampsia in Latin America and analyze biomarker and hemodynamic trends between subphenotypes after hospital admission. METHODS: A single-center prospective cohort study was conducted in Colombia. The latent class analysis identified subphenotypes using clinical variables, biomarkers, laboratory tests, and maternal hemodynamics. Class-defining variables were restricted to measurements at and 24 h after admission. Primary and secondary outcomes were severe maternal and perinatal complications. RESULTS: Among 49 patients, two subphenotypes were identified: Subphenotype 1 (34.7%) had a higher likelihood of an sFlt-1/PlGF ratio ≤ 38, maternal age > 35, and low probability of TPR > 1400, CO <8, and IUGR; Subphenotype 2 (65.3%) had a low likelihood of an sFlt-1/PlGF ratio < 38, maternal age > 35, and high probability of TPR > 1400, CO <8, and IUGR. At 24 h postadmission, 64.7% of subphenotype 1 patients changed to subphenotype 2, while 25% of subphenotype 2 patients were reclassified as subphenotype 1. Subphenotype 1 displayed significant changes in CO and TPR, while subphenotype 2 did not. Maternal complications were more prevalent in subphenotype 2, with an odds ratio of 5.3 (95% CI: 1.3-22.0; P = 0.02), but no significant differences in severe neonatal complications were observed. CONCLUSIONS: We identified two distinct subphenotypes in a Latin American cohort of patients with severe early-onset pre-eclampsia. Subphenotype 2, characterized by higher TPR, sFlt-1, and serum creatinine and lower CO and PlGF at admission, was associated with worse maternal outcomes and appeared less modifiable after in-hospital treatment.

Performance of machine-learning approach for prediction of pre-eclampsia in a middle-income country.

OBJECTIVE: Pre-eclampsia (PE) is a serious complication of pregnancy associated with maternal and fetal morbidity and mortality. As current prediction models have limitations and may not be applicable in resource-limited settings, we aimed to develop a machine-learning (ML) algorithm that offers a potential solution for developing accurate and efficient first-trimester prediction of PE. METHODS: We conducted a prospective cohort study in Mexico City, Mexico to develop a first-trimester prediction model for preterm PE (pPE) using ML. Maternal characteristics and locally derived multiples of the median (MoM) values for mean arterial pressure, uterine artery pulsatility index and serum placental growth factor were used for variable selection. The dataset was split into training, validation and test sets. An elastic-net method was employed for predictor selection, and model performance was evaluated using area under the receiver-operating-characteristics curve (AUC) and detection rates (DR) at 10% false-positive rates (FPR). RESULTS: The final analysis included 3050 pregnant women, of whom 124 (4.07%) developed PE. The ML model showed good performance, with AUCs of 0.897, 0.963 and 0.778 for pPE, early-onset PE (ePE) and any type of PE (all-PE), respectively. The DRs at 10% FPR were 76.5%, 88.2% and 50.1% for pPE, ePE and all-PE, respectively. CONCLUSIONS: Our ML model demonstrated high accuracy in predicting pPE and ePE using first-trimester maternal characteristics and locally derived MoM. The model may provide an efficient and accessible tool for early prediction of PE, facilitating timely intervention and improved maternal and fetal outcome. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Eficiencia de un enfoque de aprendizaje automático para la predicción de la preeclampsia en un país de ingresos medios OBJETIVO: La preeclampsia (PE) es una complicación grave del embarazo asociada a morbilidad y mortalidad materna y del feto. Dado que los modelos de predicción actuales tienen limitaciones y pueden no ser aplicables en situaciones con recursos limitados, se propuso desarrollar un algoritmo de aprendizaje automático (AA) que ofrezca una solución con potencial para desarrollar una predicción precisa y eficiente de la PE en el primer trimestre. MÉTODOS: Se realizó un estudio de cohorte prospectivo en Ciudad de México para desarrollar un modelo de predicción de la PE pretérmino (PEp) en el primer trimestre utilizando AA. Para la selección de variables se utilizaron las características maternas y los múltiplos de la mediana (MdM) obtenidos localmente para la presión arterial media, el índice de pulsatilidad de la arteria uterina y el factor de crecimiento placentario sérico. El conjunto de datos se dividió en subconjuntos de datos de entrenamiento, de validación y de test estadístico. Se empleó un método de red elástica para la selección de predictores, y el rendimiento del modelo se evaluó mediante el área bajo la curva de características operativas del receptor (ABC) y las tasas de detección (TD) con tasas de falsos positivos (TFP) del 10%. RESULTADOS: El análisis final incluyó a 3050 mujeres embarazadas, de las cuales 124 (4,07%) desarrollaron PE. El modelo de AA mostró una buena eficiencia, con un ABC de 0,897, 0,963 y 0,778 para la PEp, la PE de aparición temprana (PEat) y cualquier tipo de PE (todas las PE), respectivamente. Las TD con TFP del 10% fueron del 76,5%, 88,2% y 50,1% para la PEp, PEat y todas las PE, respectivamente. CONCLUSIONES: Nuestro modelo de AA demostró una alta precisión en la predicción de la PEp y la PEat utilizando características maternas del primer trimestre y MdM calculados localmente. El modelo puede proporcionar una herramienta eficiente y accesible para la predicción temprana de la PE, facilitando la intervención oportuna y la mejora de los resultados maternos y del feto.

Pre-eclampsia in low and middle-income settings: What are the barriers to improving perinatal outcomes and evidence-based recommendations?

OBJECTIVE: To discuss the points that still challenge low- and middle-income countries (LMICs) and strategies that have been studied to help them overcome these issues. METHODS: Narrative review addressing 20 years of articles concerning pre-eclampsia morbidity and mortality in LMICs. We summarized evidence-based strategies to overcome the challenges in order to reduce the pre-eclampsia impact on perinatal outcomes. RESULTS: Pre-eclampsia is the first or second leading cause in the ranking of avoidable causes of maternal death, and approximately 16% of all maternal deaths are attributable to eclampsia and pre-eclampsia. Considering the social and economic contexts, it represents a major public health concern, and prevention and early detection of pre-eclampsia seem to be a major challenge. Reducing maternal mortality related to hypertensive disturbances depends on public policies to manage these preventable conditions. Early and continuous recognition of signs of severity related to hypertensive disorders during pregnancy and childbirth, self-monitoring of symptoms and blood pressure, as well as preventive approaches such as aspirin and calcium, and magnesium sulfate, are lifesaving procedures that have not yet reached a universal scale. CONCLUSION: This review provides a vision of relevant points to support pregnant women in overcoming the constraints to healthcare access in LMICs, and strategies that can be applied in primary prenatal care units.

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

Complicaciones anestésicas en pacientes con preeclampsia con criterios de severidad / Anesthetic complications in patients with preeclampsia with severity criteria

Resumen OBJETIVO: Describir las complicaciones anestésicas en pacientes con preeclampsia con criterios de severidad. MATERIALES Y MÉTODOS: Estudio observacional, retrospectivo, transversal y descriptivo llevado a cabo en un centro de atención terciaria de la ciudad de Medellín, Colombia, entre enero de 2016 y enero de 2021. La fuente de información fueron las historias clínicas. Criterios de inclusión: pacientes embarazadas, con preeclampsia con criterios de severidad que recibieron anestesia neuroaxial o general. Criterios de exclusión: pacientes con diagnóstico previo de coagulopatías y con otros trastornos hipertensivos del embarazo no relacionados con la preeclampsia con características graves. Se hizo un muestreo no probabilístico de casos consecutivos y un análisis univariado. RESULTADOS: Se incluyeron 508 pacientes; el 69% finalizaron el embarazo mediante cesárea. El 89.4% recibió anestesia neuroaxial y el 10.6% anestesia general. El 29.9% ingresó a cuidados intensivos, 4.7% tuvo hipotensión, 3.9% requirió soporte vasopresor, 3.7% con vía aérea difícil, 0.98% requirió ventilación mecánica. Una paciente resultó con edema pulmonar y otra con accidente cerebrovascular hemorrágico. El 1.5% de quienes recibieron anestesia espinal tuvo retención urinaria. La frecuencia de anestesia neuroaxial fallida fue del 1.4% para parto y 1.3% para cesárea. No se registraron casos de muerte, meningitis, aracnoiditis, paraplejia, punción de la duramadre accidental o reacción alérgica. CONCLUSIONES: La anestesia neuroaxial sigue siendo la técnica anestésica de elección en pacientes con preeclampsia con criterios de severidad. Las complicaciones anestésicas evidenciadas con más frecuencia fueron el ingreso a cuidados intensivos, hipotensión y requerimiento de soporte vasopresor.

Abstract OBJECTIVE: To describe anesthetic complications in patients with pre-eclampsia with severity criteria. MATERIALS AND METHODS: Observational, retrospective, cross-sectional, descriptive study conducted in a tertiary care center in the city of Medellin, Colombia, between January 2016 and January 2021. The source of information was medical records. Inclusion criteria: pregnant patients, with pre-eclampsia with severity criteria, who received neuroaxial or general anesthesia. Exclusion criteria: patients with previous diagnosis of coagulopathies and with other hypertensive disorders of pregnancy unrelated to pre-eclampsia with severe characteristics. Non-probability sampling of consecutive cases and univariate analysis were performed. RESULTS: Fifty-eight patients were included; 69% terminated the pregnancy by cesarean section. Eighty-nine.4% received neuroaxial anesthesia and 10.6% general anesthesia. 29.9% were admitted to intensive care, 4.7% had hypotension, 3.9% required vasopressor support, 3.7% had difficult airway, 0.98% required mechanical ventilation. One patient had pulmonary edema and one patient had hemorrhagic stroke. Urinary retention occurred in 1.5% of patients receiving spinal anesthesia. The incidence of failed neuroaxial anesthesia was 1.4% for labor and 1.3% for cesarean section. There were no cases of death, meningitis, arachnoiditis, paraplegia, accidental dura puncture, or allergic reaction. CONCLUSIONS: Neuroaxial anesthesia remains the anesthetic technique of choice in patients with pre-eclampsia with severity criteria. The most common anesthetic complications were ICU admission, hypotension, and need for vasopressor support.

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.

How can we reduce maternal mortality due to preeclampsia? The 4P rule

Abstract In low and middle-income countries such as Brazil, most maternal deaths are related to hypertensive complications. Preeclampsia is the leading cause of maternal mortality and morbidity. Significant proportion is associated with the following factors: lack of identification of high-risk women, lack of adequate prevention, difficulty in maintaining a high-risk prenatal follow-up, delayed diagnosis, insecurity and low use of magnesium sulphate, delayed pregnancy interruption and lack of postpartum follow-up of these high-risk cases. Four major actions are proposed to minimize this alarming clinical picture and reduce the mortality rates due to preeclampsia, called the "4 P Rule" (Adequate Prevention - Vigilant Prenatal Care - Timely Delivery (Parturition) - Safe Postpartum). From this simple "rule" we can open a range of important processes and reminders that may help in the guidance of preeclampsia management.

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.

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

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/ß-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/ß-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/ß-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/ß-catenin pathway in preeclampsia rats, thereby improving perinatal outcomes in PE rats.

[Inflammatory indexes and their association with the severity of preeclampsia]. / Índices inflamatorios y su asociación con la severidad de la preeclampsia.

Background: Recent studies have confirmed the relationship between some inflammatory indexes and preeclampsia (PE); however, they have not been analyzed in PE with and without severity criteria. Objective: To know the association between inflammatory indexes and the severity of PE. Material and methods: Analytical cross-sectional prolective study. Pregnant patients were included, divided into group 1 (PE without severity criteria); group 2 (PE with severity criteria); group 3 (normotensive pregnant women). Records were reviewed and inflammatory indexes [(neutrophil-lymphocyte ratio [NLR], platelet-lymphocyte ratio [PLR], lymphocyte-monocyte ratio [LMR] and systemic immune index [SII]) were calculated. Results: 240 patients were analyzed, 80 per group; age 28 (IQR 27-29) years. A significant difference was observed between group 1, group 2 and group 3, NLR 3.29 (IQR 2.82-3.69), 3.59 (IQR 2.83-4.2) and 3.42 (IQR 3.17-3.92), respectively, p = 0.02; PLR 121.59 (IQR 103.78-132), 108.32 (IQR 92.96-127.43) 136 (IQR 115.18-157.56), respectively, p = 0.01; LMR and SII showed no difference between the groups. LMR made possible to distinguish PE with and without severity criteria, cut-off point of ≥ 3.20, sensitivity 56%, specificity 56%, AUC 0.56, p = 0.01, and cut-off point ≥ 3.24, sensitivity 58%, specificity 58%, AUC 0.57, p = 0.04, respectively; the LMR ≥ 3.24 was associated with PE without severity criteria (OR 2.02 [95%CI 1.08-3.80], p = 0.03). Conclusions: The MLR was the only inflammatory index analyzed that was associated with the presence of PE without severity data. No inflammatory index was associated with PE with severity data.

Introducción: estudios recientes han confirmado la relación que existe entre algunos índices inflamatorios y la preeclampsia (PE); sin embargo, no se han analizado en la PE con y sin criterios de severidad. Objetivo: conocer la asociación entre los índices inflamatorios y la severidad de la PE. Material y métodos: estudio transversal analítico prolectivo. Se incluyeron pacientes embarazadas, distribuidas en PE sin criterios de severidad (grupo 1), PE con criterios de severidad (grupo 2) y normotensión (grupo 3). Se revisaron expedientes y se calcularon los índices inflamatorios (índice neutrófilos linfocitos [INL], plaquetas linfocitos [IPL], linfocito monocito [ILM] e inmunosistémico [IIS]). Resultados: se analizaron 240 pacientes, 80 por grupo; edad de 28 años (RIC 27-29). Se observó diferencia significativa entre grupo 1, grupo 2 y grupo 3, INL 3.29 (RIC 2.82-3.69), 3.59 (RIC 2.83-4.2) y 3.42 (RIC 3.17-3.92), respectivamente, p = 0.02; IPL 121.59 (RIC 103.78-132), 108.32 (RIC 92.96-127.43) 136 (RIC 115.18-157.56), respectivamente, p = 0.01; ILM y ISS no mostraron diferencia entre los grupos. ILM permitió distinguir PE con y sin criterios de severidad, punto de corte ≥ 3.20, sensibilidad 56%, especificidad 56%, AUC 0.56, p = 0.01, y, punto de corte ≥ 3.24, sensibilidad 58%, especificidad 58%, AUC 0.57, p = 0.04, respectivamente; el ILM ≥ 3.24 se asoció con PE sin criterios de severidad (RM 2.02 [IC 95% 1.08-3.80], p = 0.03). Conclusiones: el ILM fue el único índice inflamatorio analizado que se asoció con la presencia de PE sin criterios de severidad. Ningún índice inflamatorio se asoció con la PE con datos de severidad.