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

Resultados maternos y fetales en mujeres embarazadas con enfermedad renal crónica basada en la tasa de filtración glomerular / Maternal And Fetal Outcomes In Pregnant Women With Chronic Kidney Disease Based On Glomerular Filtration Rate

Introducción: el embarazo causa adaptaciones en el riñón, tanto en anatomía como en función, para mantener el entorno extracelular, hemodinámico y hormonal. Sin embargo, estos pueden no llevarse a cabo de manera completamente óptima en presencia de enfermedad renal. El objetivo era estudiar la relación entre la enfermedad renal y los resultados maternos de fetal durante el embarazo, asociado con un rechazo por paciente y/o en relación con el tratamiento especializado. Material y métodos: estudio observacional y retrospectivo en una serie de casos, revisando 134 archivos de pacientes embarazadas con cierto grado de enfermedad renal antes del embarazo. Los resultados maternos registrados fueron: enfermedad hipertensiva durante el embarazo, deterioro renal agudo, necesidad de terapia de sustitución renal y en productos: prematuridad, restricción del crecimiento intrauterino, muerte fetal y aborto espontáneo. Resultados: Resultados maternos: tasa media de filtración glomerular (GFR) de 58.23 ml/min, aumento de peso de 7 kg; La preeclampsia fue diagnosticada en 92 mujeres (55 severas). 46 pacientes mostraron lesión renal aguda, 40 se resolvieron conservativamente; 1 requirió diálisis peritoneal y 15 hemodiálisis (con una decisión retrasada un promedio de un mes por rechazo por paciente y/o pariente). La resolución del embarazo fue por cesárea en 111 pacientes; Nacieron 116 productos antes de las 37 semanas de gestación, con un peso promedio de 1910 g, 94 mostraron restricción del crecimiento intrauterino. Conclusión: la enfermedad renal influyó directamente en el mayor número de resultados adversos maternos y fetales cuando se rechazó la atención médica especializada. Existe una correlación entre el ligero estado de Davison con los estados I, II y IIIA de Kdigo en el análisis de correspondencia

Introduction: Pregnancy causes adaptations in the kidney, both in anatomy and function, to maintain the extracellular, hemodynamic and hormonal environment. However, these may not be carried out completely optimally in the presence of kidney disease. The objective was to study the relation between kidney disease and maternal-fetal outcomes during pregnancy, associated with a rejection by patient and/or relative to specialized treatment. Material and Methods: Observational, retrospective study in a series of cases, reviewing 134 files of pregnant patients with some degree of kidney disease prior to pregnancy. Maternal outcomes recorded were: hypertensive disease during pregnancy, acute renal deterioration, need for renal substitution therapy, and in products: prematurity, restriction of intrauterine growth, fetal death and miscarriage. Results: Maternal outcomes: mean glomerular filtration rate (GFR) of 58.23ml/min, weight gain of 7 kg; preeclampsia was diagnosed in 92 women (55 severe). 46 patients showed acute renal lesion, 40 were conservatively resolved; 1 required peritoneal dialysis and 15 hemodialysis (with decision delayed an average of one month by rejection by patient and/or relative). Resolution of pregnancy was by cesarean in 111 patients; 116 products were born before 37 weeks of gestation, with average weight of 1910 g, 94 showed restriction of intrauterine growth. Conclusion: Kidney disease directly influenced the greater number of adverse maternal and fetal outcomes when specialized medical care was rejected. There is a correlation between slight Davison state with states I, II and IIIa of KDIGO in correspondence analysis.

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)

Uso de labetalol frente a nifedipino en la preeclampsia / Use of labetalol vs nifedipine in preeclampsia

Fundamento: La preeclampsia es un estado de vasoconstricción generalizado asociado a la disfunción del epitelio vascular en vez de vasodilatación propia del embarazo, caracterizada por la hipertensión proteinuria a partir de la semana 20, acompañada a veces de edemas; asimismo constituye un peligro de salud para la madre y el feto. El tratamiento clínico tradicional utiliza fármacos antihipertensivos por vía oral, entre los que se mencionan el labetalol y nifedipino de liberación prolongada. Objetivo: Analizar la efectividad del labetalol y del nifedipino como tratamiento antihipertensivo relacionado con preeclampsia. Metodología: Se recurrió a fuentes de consulta encontradas en Google Scholar, Science Direct, SciELO, Pubmed, Medes y Elsevier. De 211 fuentes se seleccionaron 31 de acuerdo con criterios de inclusión y exclusión. Conclusiones: Por consenso se ha determinado que en la mayor parte de fuentes de consulta el nifedipino por vía oral es más efectivo que el labetalol en el tratamiento de la preeclampsia.

Background: Pre-eclampsia is a generalized vasoconstriction state associated with vascular epithelial dysfunction rather than the vasodilation characteristic of pregnancy, characterized by proteinuric hypertension from the 20th week of pregnancy, sometimes associated with edema; it also causes health risks to the mother and fetus. Traditional clinical treatment uses oral antihypertensive drugs, among these labetalol and extended-release nifedipine are included. Objective: To analyze the efficacy of labetalol and nifedipine as an antihypertensive treatment in pre-eclampsia. Methodology: Reference sources found in Google Scholar, Science Direct, SciELO, Pubmed, Medes and Elsevier were used. Out of 211 sources, 31 were selected according to inclusion and exclusion criteria. Conclusions: It has been determined by majority consensus that oral nifedipine is more effective than labetalol in pre-eclampsia treatment.

Tendência temporal de nascidos prematuros no estado de Santa Catarina entre 2011 e 2021 / Temporal trend of premature birth in the state of Santa Catarina between 2011 and 2021

Objetivo: Analisar a tendência temporal de nascimentos prematuros no estado de Santa Catarina entre 2011 e 2021. Métodos: Estudo observacional ecológico de tendência temporal realizado com informações do banco de dados do Sistema de Informação sobre Nascidos Vivos do estado de Santa Catarina (2011-2021), disponibilizado pela Diretoria de Vigilância Epidemiológica. Foram analisados todos os nascidos vivos prematuros segundo o ano de processamento e o local de residência em Santa Catarina (110.422). Foram incluídos os nascidos vivos de gestação com menos de 37 semanas completas. As taxas de nascimentos prematuros foram calculadas proporcionalmente à totalidade de nascimentos e calculadas segundo macrorregião, idade materna, número de consultas do pré-natal, instrução materna e cor de pele. Para o cálculo da tendência temporal, foi utilizada a regressão linear simples, com intervalo de confiança de 95% (p ≤ 0,05). Resultados: A taxa média de nascimentos prematuros no estado de Santa Catarina foi de 10,57%, com tendência estável (p < 0,001). Maiores taxas específicas foram encontradas nas macrorregiões Meio Oeste e Serra e Planalto Norte e Nordeste (11,46%), extremos de idade (10-14 anos e 45-64 anos) e menor escolaridade. Maior número de consultas de pré-natal apresentou taxa de prematuridade menor (7,69%). Tendências crescentes das taxas foram apenas encontradas na macrorregião Grande Oeste, faixa etária materna entre 40-44 anos e entre 4-6 consultas de pré-natal. Conclusão: A tendência da taxa de prematuridade manteve-se estável em Santa Catarina. Baixo número de consultas de pré-natal, extremos de idades e baixa escolaridade mostraram taxas maiores de prematuridade. (AU)

Objective: Analyzing the temporal trend of premature births in the state of Santa Catarina between 2011 and 2021. Methods: Observational ecological temporal trend study carried out with information from the database of the Information System on Live Births in the state of Santa Catarina (2011-2021), made available by the Epidemiological Surveillance Directorate. All premature live births were analyzed according to the year of processing and place of residence in Santa Catarina (110,422). Live births of less than 37 completed weeks were included. The rates of premature births were calculated in proportion to the total number of births and calculated according to macro-region, maternal age, number of prenatal consultations, maternal education and skin color. Simple linear regression was used to calculate the temporal trend, with a confidence interval of 95% (p ≤ 0.05). Results: The average rate of premature births in the state of Santa Catarina was 10.57%, with a stable trend (p < 0.001). Higher specific rates were found in the Midwest and Serra, North Plateau and Northeast macro-regions (11.46%), age extremes (10-14 years and 45-64 years) and lower schooling. A greater number of prenatal consultations had a lower prematurity rate (7.69%). Increasing trends in rates were only found in the Grande Oeste macro-region, maternal age group between 40-44 years and between 4-6 prenatal consultations. Conclusion: The prematurity rate trend remained stable in Santa Catarina. Low number of prenatal consultations, extremes of age and low education showed higher rates of prematurity. (AU)

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.

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.

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

Importancia de la prevención y detección oportuna de la preeclampsia/eclampsia / Importance of prevention and timely detection of preeclampsia/eclampsia

La preeclampsia/eclampsia constituyen una manifestación de la enfermedad hipertensiva que se puede presentar después de la semana 20 del embarazo. Esta tiene la capacidad de generar múltiples complicaciones en la gestante y el feto. Su diagnóstico oportuno y la toma de medidas preventivas ante sus factores de riesgo tienen la potencialidad para reducir la morbimortalidad por esta causa.

Preeclampsia/eclampsia is a manifestation of a hypertensive disease that can occur after the 20th week of pregnancy by generating multiple complications in the pregnant woman and the fetus. Its timely diagnosis and the taking of preventive measures against its risk factors can reduce morbidity and mortality.

Association of Vitamin D supplementation in pre-eclampsia: Systematic review and meta-analysis / Philippine Journal of Obstetrics and Gynecology

Introduction@#In the Philippines, hypertensive diseases of pregnancy belong in the top three causes of maternal mortality and complicate up to 10% of pregnancy worldwide. In relation with this, proper interventions must be given during the prenatal check-up to prevent occurrence that may cause feto-maternal mortality and morbidity. During prenatal check-up, pregnant women are given vitamin and mineral supplementations. Vitamin D has an association of having a risk for preeclampsia. Receptors of Vitamin D and 1-a hydroxylase are both expressed in the decidua and trophoblast cells. The active form of Vitamin D affects the transcription and function of genes associated with angiogenesis, invasion of the placenta, and normal implantation. The mechanisms mentioned are all involved in the pathophysiology of preeclampsia.@*Objectives@#The primary outcome of this study is to determine the association of Vitamin D supplementation in preeclampsia. Specifically, this study aims to compare the following secondary outcomes: Maternal outcomes (complication of gestational diabetes mellitus and underwent cesarean delivery) and fetal outcomes (preterm delivery and birth weight).@*Methodology@#Meta-analysis and systematic review of eight randomized controlled trials.@*Results@#Vitamin D reduced the risk of preeclampsia (risk ratio [RR] 0.45, 95% confidence interval [CI] 0.30–0.69; P = 0.0002). No significant difference on risk of gestational diabetes mellitus (RR 0.84, 95% CI 0.48–1.48) and risk of preterm delivery (RR 0.71, 95% CI 0.49–1.03). Results showed that newborns of mothers who had no Vitamin D supplementation had a higher birthweight (P = 0.010). No significant difference on cesarean section rate (RR 1.12, 95% CI 0.87–1.45).@*Conclusion@#Evidence suggests that Vitamin D supplementation can reduce the risk of preeclampsia. This study encourages obstetricians in our country to add Vitamin D supplementation as prenatal medication to prevent preeclampsia, thereby reducing maternal morbidity and mortality.

Circular RNA expression profiles and circRNA-miRNA-mRNA crosstalk in pre-eclamptic placenta / 中华妇产科杂志

Objective: To identify the expression profile of circular RNA (circRNA) in placenta of pre-eclampsia (PE) pregnant women by high-throughput sequencing, and to construct the circRNA-microRNA (miRNA)-messenger RNA (mRNA) interaction network, so as to reveal the related pathways and regulatory mechanisms of PE. Methods: The clinical data and placentas of 42 women with PE (PE group) and 30 normal pregnant women (control group) who delivered in West China Second University Hospital from November 2019 to June 2021 were collected. (1) High-throughput sequencing was used to establish the differentially expressed circRNA profiles in placental tissues of 5 pairs of PE group and the control group. (2) Real-time quantitative PCR (qRT-PCR) was used to verify the expression levels of 6 differentially expressed circRNAs in placental tissues of PE group and control group. (3) Bioinformatics analysis was used to predict the target miRNA and analyze the co-expressed mRNA to construct a competitive endogenous RNA (ceRNA) network. The differentially expressed circRNAs were analyzed by Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathways. (4) Logistic regression analysis, Pearson correlation and Kendall's tau-b correlation analysis were used to test the correlation between the three differentially expressed circRNAs and the risk of PE and clinical characteristics. (5) circRNA_05393 was selected for subsequent functional study. Small interfering RNA (siRNA) and overexpression plasmid were used to knock down or increase the expression level of circRNA_05393 in trophoblast cell line HTR-8/SVneo cells, respectively. Transwell assay was used to detect the migration and invasion ability of the trophoblasts in vitro. Cell counting kit-8 assay was used to detect the proliferation ability of the trophoblasts. Results: (1) Seventy-two differentially expressed circRNAs were identified by high-throughput sequencing, of which 35 were up-regulated and 37 were down-regulated. (2) qRT-PCR showed that compared with the control group, circRNA_00673 (1.306±0.168 vs 2.059±0.242; t=2.356, P=0.021) and circRNA_07796 (1.275±0.232 vs 1.954±0.230; t=2.018, P=0.047) were significantly increased, while circRNA_05393 (1.846±0.377 vs 0.790±0.094; t=3.138, P=0.002) was significantly decreased. (3) The circRNA-miRNA-mRNA interaction network contained 3 circRNAs, 8 miRNAs and 53 mRNAs. GO functional annotation analysis showed that the biological process was mainly enriched in iron ion homeostasis, membrane depolarization during action potential and neuronal action potential. In terms of cellular components, they were mainly enriched in cytoskeleton and membrane components. In terms of molecular function, they were mainly enriched in the activity of voltage-gated sodium channel and basic amino acid transmembrane transporter. KEGG pathway enrichment analysis showed that mRNAs in the interaction network were mainly enriched in complement and coagulation cascade, glycine, serine and threonine metabolism, p53 signaling pathway and peroxisome proliferators-activated receptors (PPAR) signaling pathway. (4) Logistic regression analysis showed that down-regulation of circRNA_05393 expression was a risk factor for PE (OR=0.044, 95%CI: 0.003-0.596; P=0.019). Correlation analysis showed that circRNA_05393 was significantly correlated with systolic blood pressure and diastolic blood pressure in PE pregnant women (both P<0.05). (5) Knock down or overexpression of circRNA_05393 significantly reduced or increased the migration and invasion abilities of HTR-8/SVneo cells (all P<0.05), but had no significant effect on the ability of tube formation and proliferation (all P>0.05). Conclusions: The construction of circRNA expression profile in placenta and the exploration of circRNA-miRNA-mRNA interaction network provide the possibility to reveal the regulatory mechanism of specific circRNA involved in PE. Inhibition of circRNA_05393 may induce the progression of PE by reducing the migration and invasion of trophoblasts.

Clinical characteristics of severe pre-eclampsia in a single tertiary referral center of Xiamen City / 中华妇产科杂志

Objective: To explore the key points for preventing and reducing severe pre-eclampsia (SPE) and its severe complications in the tertiary medical referral system of a second-tier city by analyzing the clinical characteristics of SPE. Methods: The clinical data of 341 patients with SPE who terminated pregnancy in Women and Children's Hospital, School of Medicine, Xiamen University, from January 1, 2020 to December 31, 2022 were retrospectively analyzed, and the pre-eclampsia (PE) risk factors, clinical characteristics and severe complications of SPE between the patients referred from primary hospitals (referral group) and the patients received regular prenatal care in the tertiary referral center (central group) were compared, as well as the influence of the referral timing on the maternal and perinatal outcomes. Results: Among the 341 cases of SPE, 92 cases were in the referral group and 249 cases were in the central group. (1) Analysis of PE risk factors: there was no statistical difference in the proportion of risk factors of PE between these two groups [75.0% (69/92) vs 71.9% (179/249); χ2=0.328, P=0.567]. (2) Analysis of clinical features: the gestational ages at the PE early warning factors onset, at the PE first symptom onset and at SPE diagnosed, pregnancy terminated and onset of SPE severe complications in the referral group were significantly earlier than those in the central group (all P<0.05), the proportions of terminating pregnancy before 32 weeks of gestation, between 32 and 34 weeks of gestation, intensive care unit (ICU), neonatal ICU hospitalization and fetal growth restriction in single pregnancies were higher than those in the central group, while the live birth rate was lower than that in the central group (all P<0.05). (3) Analysis of SPE severe complications: the rates of SPE severe complications in the referral group was higher than that in the central group [28.3% (26/92) vs 13.7% (34/249); χ2=9.885, P=0.002]. Among them, the rates of placental abruption [7.6% (7/92) vs 2.8% (7/249); χ2=3.927, P=0.048] and still birth [6.5% (6/92) vs 0.4% (1/249); χ2=9.656, P=0.002] in the referral group were significantly higher than those in the central group. (4) Analysis of referral timings: the timings included referral after onset of SPE severe complications (9.8%, 9/92), referral after SPE diagnosed (63.0%, 58/92), referral after detection of SPE early warning signs (20.7%, 19/92) and referral after detection of PE risk factors (6.5%, 6/92). The gestational ages at SPE diagnosed and pregnancy terminated in group of referral after onset of SPE severe complications and group of referral after SPE diagnosed were significantly earlier than those in group of referral after detection of PE early warning signs and group of referral after detection of PE risk factors (P<0.05). The earlier the referral, the higher the live birth rates (P<0.05). Conclusions: The tertiary referral center of the second-tier city plays an important role in reducing the maternal and perinatal damage of PE. The timing of referral in primary medical institutions is the key point of reducing the occurrence of SPE severe complications and maternal, perinatal damage of PE. It is necessary for medical institutions of all levels in all regions to improve the ability of early identification and early intervention for PE, to enhance the awareness of SPE and its severe complications prevention and control. Primary medical institutions should especially pay attention to raise the consciousness of PE risk factors and early warning signs, and to improve the ability of PE risk factors and early warning signs screening.

Regional analysis of high risk factors of hypertensive disorders in pregnancy with organ or system impairment / 中华妇产科杂志

Objective: To explore the influencing factors of pregnancy-induced hypertensive disorders in pregnancy (HDP) with organ or system impairment in pregnant women, and to analyze and compare the differences of HDP subtypes in different regions of China. Methods: A total of 27 680 pregnant women with HDP with complete data from 161 hospitals in 24 provinces, autonomous regions and municipalities were retrospectively collected from January 1, 2018 to December 31, 2018. According to their clinical manifestations, they were divided into hypertension group [a total of 10 308 cases, including 8 250 cases of gestational hypertension (GH), 2 058 cases of chronic hypertension during pregnancy] and hypertension with organ or system impairment group [17 372 cases, including 14 590 cases of pre-eclampsia (PE), 137 cases of eclampsia, 2 645 cases of chronic hypertension with PE]. The subtype distribution of HDP in East China (6 136 cases), North China (4 821 cases), Central China (3 502 cases), South China (8 371 cases), Northeast China (1 456 cases), Southwest China (2 158 cases) and Northwest China (1 236 cases) were analyzed. By comparing the differences of HDP subtypes and related risk factors in different regions, regional analysis of the risk factors of HDP pregnant women with organ or system impairment was conducted. Results: (1) The proportions of HDP pregnant women with organ or system impairment in Northeast China (79.05%, 1 151/1 456), Central China (68.42%, 2 396/3 502) and Northwest China (69.34%, 857/1 236) were higher than the national average (62.76%, 17 372/27 680); the proportions in North China (59.18%, 2 853/4 821), East China (60.85%, 3 734/6 136) and South China (59.56%, 4 986/8 371) were lower than the national average, and the differences were statistically significant (all P<0.05). (2) Univariate analysis showed that the proportions of primiparas, non-Han, non-urban household registration, irregular prenatal examination and PE history in the hypertension with organ or system impairment group were higher than those in the hypertension group, and the differences were statistically significant (all P<0.05). Multivariate logistic regression analysis showed that primiparas, non-Han, non-urban household registration, irregular prenatal examination and PE history were independent risk factors for HDP pregnant women with organ or system impairment (all P<0.05). (3) Primipara: the rates of primipara in Northeast China, North China and Southwest China were higher than the national average level, while those in South China, Central China and Northwest China were lower than the national average level. Non-Han nationality: the rates of non-Han nationality in Northeast China, North China and Northwest China were higher than the national average, while those in East China, South China and Central China were lower than the national average. Non-urban household registration: the rates of non-urban household registration in Northeast China, North China, and Southwest China were lower than the national average, while those in East China, Central China were higher than the national average. Irregular prenatal examination: the rates of irregular prenatal examination in North China, South China and Southwest regions were lower than the national average level, while those in Northeast China, Central China and Northwest China were higher than the national average level. History of PE: the incidence rates of PE in Northeast China, North China, South China and Southwest China were lower than the national average level, while those in Central China and Northwest China were higher than the national average level. Conclusions: Primiparas, non-Han, non-urban household registration, irregular prenatal examination, and PE history are risk factors for HDP pregnant women with organ or system impairment. Patients in Northeast, Central and Northwest China have more risk factors, and are more likely to be accompanied by organ or system function damage. It is important to strengthen the management of pregnant women and reduce the occurrence of HDP.

Establishment method and significance of birthweight curve and reference in single center / 中华妇产科杂志

Objective: To establish neonatal birthweight percentile curves based on single-center cohort database using different methods, compare them with the current national birthweight curves and discuss the appropriateness and significance of single-center birthweight standard. Methods: Based on a prospective first-trimester screening cohort at Nanjing Drum Tower Hospital from January 2017 to February 2022, the generalized additive models for location, scale and shape (GAMLSS) and semi-customized method were applied to generate local birthweight percentile curves (hereinafter referred to as the local GAMLSS curves, semi-customized curves) for 3 894 cases who were at low risk of small for gestation age (SGA) and large for gestation age (LGA). Infants were categorized as SGA (birth weight<10th centile) by both semi-customized and local GAMLSS curves, semi-customized curves only, or not SGA (met neither criteria). The incidence of adverse perinatal outcome between different groups was compared. The same method was used to compare the semi-customized curves with the Chinese national birthweight curves (established by GAMLSS method as well, hereinafter referred to as the national GAMLSS curves). Results: (1) Among the 7 044 live births, 404 (5.74%, 404/7 044), 774 (10.99%, 774/7 044) and 868 (12.32%, 868/7 044) cases were diagnosed as SGA according to the national GAMLSS curves, the local GAMLSS curves and the semi-customized curves respectively. The birth weight of the 10th percentile of the semi-customized curves was higher than that of the local GAMLSS curves and the national GAMLSS curves at all gestational age. (2) When comparing semi-customized curves and the local GAMLSS curves, the incidence of admission to neonatal intensive care unit (NICU) for more than 24 hours of infants identified as SGA by semi-customized curves only (94 cases) and both semi-customized and local GAMLSS curves (774 cases) was 10.64% (10/94) and 5.68% (44/774) respectively, both significantly higher than that in non SGA group [6 176 cases, 1.34% (83/6 176); P<0.001]. The incidence of preeclampsia, pregnancy<34 weeks, and pregnancy<37 weeks of infants identified as SGA by the semi-customized curves only and both semi-customized and local GAMLSS curves was 12.77% (12/94) and 9.43% (73/774), 9.57% (9/94) and 2.71% (21/774), 24.47% (23/94) and 7.24% (56/774) respectively, which were significantly higher than those of the non SGA group [4.37% (270/6 176), 0.83% (51/6 176), 4.23% (261/6 176); all P<0.001]. (3) When comparing semi-customized curves and the national GAMLSS curves, the incidence of admission to NICU for more than 24 hours of infants identified as SGA by semi-customized curves only (464 cases) and both semi-customized and national GAMLSS curves (404 cases) was 5.60% (26/464) and 6.93% (28/404) respectively, both significantly higher than that in non SGA group [6 176 cases, 1.34% (83/6 176); all P<0.001]. The incidence of emergency cesarean section or forceps delivery for non-reassuring fetal status (NRFS) in infants identified as SGA by semi-customized curves only and both semi-customized and national GAMLSS curves was 4.96% (23/464) and 12.38% (50/404), both significantly higher than that in the non SGA group [2.57% (159/6 176); all P<0.001]. The incidence of preeclampsia, pregnancy<34 weeks, and pregnancy<37 weeks in the semi-customized curves only group and both semi-customized and national GAMLSS curves group was 8.84% (41/464) and 10.89% (44/404), 4.31% (20/464) and 2.48% (10/404), 10.56% (49/464) and 7.43% (30/404) respectively, all significantly higher than those in the non SGA group [4.37% (270/6 176), 0.83% (51/6 176), 4.23% (261/6 176); all P<0.001]. Conclusion: Compared with the national GAMLSS birthweight curves and the local GAMLSS curves, the birth weight curves established by semi-customized method based on our single center database is in line with our center' SGA screening, which is helpful to identify and strengthen the management of high-risk infants.

Association between coagulation function indicators and placental abruption among preeclampsia-eclampsia pregnant women / 中华预防医学杂志

Objective: To explore the association between coagulation function indicators and placental abruption (PA) in different trimesters of pregnancy among preeclampsia-eclampsia pregnant women. Methods: From February 2018 to December 2020, pregnant women who participated in the China birth cohort study and were diagnosed with preeclampsia, eclampsia and chronic hypertension with superimposed preeclampsia in Beijing Obstetrics and Gynecology Hospital were enrolled in this study. The baseline and follow-up information were collected by questionnaire survey, and the coagulation function indicators in the first and third trimesters were obtained through medical records. The Cox proportional hazards model was used to analyze the association between the coagulation function indicators and PA. A restrictive cubic spline curve was used to draw the dose-response curve between the relevant coagulation function indicators and PA. Results: A total of 1 340 participants were included in this study. The age was (32.50±4.24) and the incidence of PA was 4.4% (59/1 340). After adjusting for relevant factors, Cox proportional hazards model showed that compared with the high-level classification of fibrinogen (FIB), participants within the middle-(HR=3.28, 95%CI: 1.27-8.48) and low-level (HR=3.84, 95%CI: 1.40-10.53) classification during the first trimester and within the low-level classification (HR=4.18, 95%CI: 1.68-10.39) during the third trimester were more likely to experience PA. Compared with the middle-level classification of pro-thrombin time (PT), the risk of PA in the participants within the low-level classification (HR=2.67, 95%CI: 1.48-4.82) was significantly higher in the third trimester. The restrictive cubic spline analysis showed a linear negative association between FIB and PA in the first and third trimesters, while PT and PA showed an approximately L-shaped association . Conclusion: Among pregnant women diagnosed with preeclampsia-eclampsia, the middle-and low-level classification of FIB in the first and third trimesters and the low-level classification of PT in the third trimester could increase the risk of PA.

Analysis of incidence and associated factors of preterm birth based on pre-pregnancy body mass index stratification / 中华预防医学杂志

Objective: To analyze the incidence of preterm birth based on pre-pregnancy body mass index (BMI) stratification and explore the associated factors of preterm birth among pregnant women at different BMI stratifications. Methods: From February 2018 to December 2020, pregnant women who participated in China Birth Cohort Study (CBCS) and gave birth at Beijing Obstetrics and Gynecology Hospital were enrolled as the study subjects. Electronic Data Capture System and standard structured questionnaires were used to collect data related to pre-pregnancy, pregnancy, and delivery for pregnant women. Pregnant women were divided into the low-weight group, normal-weight group and overweight group based on their pre-pregnancy BMI. A Cox proportional hazards model was used to analyze the associated factors of preterm birth among pregnant women with different BMI before pregnancy. Results: A total of 27 195 singleton pregnant women were included, with a preterm birth rate of 5.08% (1 381/27 195). The preterm birth rates in the low-weight group, normal-weight group and overweight group were 4.29% (138/3 219), 4.63% (852/18 390) and 7.00% (391/5 586) respectively (P<0.001). After adjusting for relevant factors, the Cox proportional hazards model showed that the risk of preterm birth in the overweight group was 1.457 times higher than that in the normal-weight group (95%CI: 1.292-1.643). Preeclampsia-eclampsia (HR=2.701, 95%CI: 1.318-5.537) was the associated factor for preterm birth in the low-weight group. Advanced maternal age (HR=1.232, 95%CI: 1.054-1.441), history of preterm birth (HR=4.647, 95%CI: 3.314-6.515), vaginal bleeding in early pregnancy (HR=1.613, 95%CI: 1.380-1.884), and preeclampsia-eclampsia (HR=3.553, 95%CI: 2.866-4.404) were associated factors for preterm birth in the normal-weight group. Advanced maternal age (HR=1.473, 95%CI: 1.193-1.818), history of preterm birth (HR=3.209, 95%CI: 1.960-5.253), vaginal bleeding in early pregnancy (HR=1.636, 95%CI: 1.301-2.058), preeclampsia-eclampsia (HR=2.873, 95%CI:2.265-3.643), and pre-gestational diabetes mellitus (HR=1.867, 95%CI: 1.283-2.717) were associated factors for preterm birth in the overweight group. Conclusion: Pre-pregnancy overweight is an associated factor for preterm birth, and there are significant differences in the associated factors of preterm birth among pregnant women with different BMI before pregnancy.

Association between blood pressure during 12-28 weeks gestation and pre-eclampsia: predictive value of blood pressure trajectories constructed by latent class growth modeling / 中华心血管病杂志

Objective: To explore the associations between blood pressure trajectories during pregnancy and risk of future pre-eclampsia in a large cohort enrolling pregnant women at gestational age of ~12 weeks from community hospitals in Tianjin. Latent class growth modeling (LCGM) was used to model the blood pressure trajectories. Methods: This was a large prospective cohort study. The study enrolled pregnant women of ~12 weeks of gestation in 19 community hospitals in Tianjin from November 1, 2016 to May 30, 2018. We obtained related information during 5 antepartum examinations before gestational week 28, i.e., week 12, week 16, week 20, week 24 and week 28. LCGM was used to model longitudinal systolic (SBP) and diastolic blood pressure (DBP) trajectories. For the association study, the predictors were set as SBP and DBP trajectory membership (built separately), the outcome was defined as the occurrence of preeclampsia after 28 weeks of gestation. Results: A total of 5 809 cases with known pregnant outcomes were documented. After excluding 249 cases per exclusion criteria, 5 560 cases with singleton pregnancy were included for final analysis. There were 128 cases preeclampsia and 106 cases gestational hypertension in this cohort. Univariate logistic regression and multivariate logistic regression showed the higher baseline SBP level and DBP level were related with increased risk of preeclampsia. Four distinctive SBP trajectories and DBP trajectories from 12 weeks to 28 weeks of gestation were identified by LCGM. After controlling for potential confounders (baseline BMI, being primipara or not, white blood cell counts, hemoglobin level, platelet counts and alanine aminotransferase level), the OR for SBP latent classification trajectory_ 4 was 4.023 (95%CI: 2.368 to 6.835, P<0.001), and the OR for SBP latent classification trajectory_3 was 1.854 (95%CI: 1.223 to 2.811, P=0.004). Logistic regression showed that: using the DBP latent classification trajectory_1 as the reference group, the OR for DBP latent classification trajectory_4 was 4.100 (95%CI: 2.571 to 6.538, P<0.001), and 2.632 (95%CI: 1.570 to 4.414, P<0.001) for DBP latent classification trajectory_2. After controlling for potential confounders (baseline BMI, being primipara or not, white blood cell counts, hemoglobin level, platelet counts and alanine aminotransferase level), the OR for DBP_traj_4 was 2.527 (95%CI: 1.534 to 4.162, P<0.001), and the OR for DBP_traj_3 was 1.297 (95%CI: 0.790 to 2.128, P=0.303), and 2.238 (95%CI: 1.328 to 3.772, P=0.002) for DBP_traj_2. Therefore, BP trajectories from 12 weeks to 28 weeks identified by LCGM served as novel risk factors that independently associated with the occurrence of preeclampsia. Receiver operating characteristic (ROC) curve analysis showed incremental diagnostic performance by combing baseline blood pressure levels with blood pressure trajectories. Conclusion: By applying LCGM, we for the first time identified distinctive BP trajectories from gestational week 12 to 28, which can independently predict the development of preeclampsia after 28 weeks of gestation.

Histopathological, ultrastructural, and immunohistochemical examination of changes in the placenta as a result of severe preeclampsia

Purpose: To investigate the role of hypoxia-inducible transcription factor-1 alpha (HIF-1α) and angiogenetic factor endothelin-1 (ET-1) expression in regulating hypoxia and placental development by routine histopathological methods. Methods: Twenty preeclamptic and normal placentas were used. Placenta tissue pieces were examined histopathologically after routine paraffin follow-ups. HIF-1α and ET-1 proteins were examined immunohistochemically, and placental tissues were examined ultrastructurally. Results: Increase in syncytial proliferation, endothelial damage in vessels, and increase in collagen were observed in preeclamptic placentas. As a result of preeclampsia, an increase was observed in HIF-1α and ET-1 protein levels in the placenta. Dilatation of endoplasmic reticulum and loss of cristae in mitochondria were observed in trophoblast cells in preeclamptic placental sections. Conclusion: High regulation of oxygen resulting from preeclampsia has been shown to be a critical determinant of placentagenesis and plays an important role in placental differentiation, changes in maternal and fetal blood circulation, trophoblastic invasion, and syncytial node increase. It has been thought that preeclampsia affects secretion by disrupting the endoplasmic reticulum structure and induces mitochondrial damage, and that ET-1 may potentially help in the induction of stress pathways as a result of hypoxia in preeclampsia.