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Objetivo: Evaluar el valor predictivo negativo de la ratio antigénica y conocer su rentabilidad para descartar preeclampsia precoz en pacientes de alto riesgo de desarrollarla, con profilaxis de ácido acetilsalicílico. Métodos: Se realizó un estudio descriptivo transversal que recogió a las gestantes con cribado de preeclampsia precoz de alto riesgo (384 gestantes) en el Hospital Santa Lucía durante el año 2021, para lo que se usó test Elecsys® tabulado a un riesgo mayor a 1/150 en primer trimestre, y que tomaran ácido acetilsalicílico antes de la semana 16, quedando en 368 gestantes vistas en las semanas 20, 26, 31 y 36. Se realizó biometría, ratio angiogénica y doppler. Resultados: La incidencia de preeclampsia precoz en la población fue 4 casos (incidencia 1,08 %). Son significativos por su alto valor predictivo negativo del 100 % de preeclampsia precoz: la ratio angiogénica mayor a 38 en la semana 26 y el doppler de las uterinas en semana 20 y 26. Conclusión: En gestaciones con cribado de alto riesgo de preeclampsia que tomen ácido acetilsalicílico, una ratio angiogénica menor a 38 en la semana 26, además de un doppler uterino normal en semana 20 y 26 permite reducir el seguimiento gestacional(AU)
Objective: Our main objective was to evaluate the negative predictive value of the angiogenic ratio and to know its profitability to rule out early preeclampsia in patients at high risk of early preeclampsia with acetylsalicylic acid prophylaxis. Methods: A cross-sectional descriptive study was carried out that included pregnant women with high-risk early preeclampsia screening (384 pregnant women) at the Santa Lucía Hospital during the year 2021, for which the Elecsys® test tabulated at a risk >1/ was used. 150 in the first trimester, and who take acetylsalicylic acid before week 16, leaving 368 pregnant women seen in weeks 20, 26, 31 and 36, with biometry, angiogenic ratio and Doppler performed. Results: The incidence of early preeclampsia in the population was 4 cases (incidence 1.08%). They are significant due to their high negative predictive value of 100% of early preeclampsia: Angiogenic ratio > 38 in week 26, uterine Doppler in weeks 20 and 26. Conclusion: Pregnancies with high risk screening for preeclampsia who take acid acetylsalicylic acid, an angiogenic ratio < 38 at week 26 in addition to a normal uterine Doppler at weeks 20 and 26 allows for reduced gestational follow-up(AU)
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Humanos , Feminino , Gravidez , Pré-Eclâmpsia , Aspirina , Programas de Rastreamento , Valor Preditivo dos Testes , Proteínas Angiogênicas , Placenta , Primeiro Trimestre da Gravidez , Fator de Crescimento Placentário , AntígenosRESUMO
Objetivo: Determinar la frecuencia de complicaciones materno-perinatales y factores clínicos asociados a estos resultados en estantes con lupus. Métodos: Se realizó un estudio de casos y controles a partir de historias clínicas de pacientes con diagnóstico Lupus Eritematoso Sistémico en embarazo, entre 2010-2022 en una institución de salud en Medellín-Colombia. Éstas se clasificaron como casos (pacientes con resultados adversos materno-perinatales) y controles (pacientes sin resultados adversos). Resultados: Se incluyó un total de 67 pacientes (35 casos y 32 controles). Las complicaciones maternas más frecuentes fueron los trastornos hipertensivos asociados al embarazo (71,4 %), incluyendo preeclampsia y una presentación importante de partos pretérmino (68,6 %). La nefritis lúpica previa y durante el embarazo, fue más frecuente en los casos que en los controles (31,4 % versus 9,4 %). Los compromisos cardiovasculares, de mucosas y musculo-esquelético, fueron más frecuentes durante el embarazo (31,4 %, 40 % y 34,3 %, respectivamente), coincidiendo con mayor actividad del lupus, principalmente durante el embarazo. El compromiso cardiovascular y de mucosas durante el embarazo, así como tener síndrome antifosfolípido se relacionaron con desenlace materno-perinatal adverso. Conclusión: Componentes clínicos propios de la enfermedad como la nefritis lúpica, el síndrome antifosfolípido, el compromiso cardiovascular, y de mucosas podrían predisponer a desenlaces maternos y/o perinatales adversos como trastornos hipertensivos asociados al embarazo, pretérmino, restricción de crecimiento fetal, entre otros(AU)
Objective: To determine the frequency of maternal-perinatal complications and the clinical factors associated with these outcomes in pregnant women with lupus. Methods: A case-control study was conducted using the medical records of patients diagnosed with pregnancy and lupus in a healthcare institution in Medellin, Colombia, between 2010 and 2022. The patients were classified as cases (patients with adverse maternal-perinatal outcomes) and controls (patients without adverse outcomes). Results: A total of 67 patients (35 cases and 32 controls) were included. The most frequent maternal complications were pregnancyassociated hypertensive disorders (71.4%), including preeclampsia and a significant presentation of preterm deliveries (68.6%). Lupus nephritis prior to and during pregnancy was more frequent in cases than in controls (31.4% versus 9.4%). Cardiovascular, mucosal and musculoskeletal compromises were more frequent during pregnancy (31.4%, 40% and 34.3%, respectively), coinciding with greater lupus activity, mainly during pregnancy. Cardiovascular and mucosal involvement during pregnancy, as well as having antiphospholipid syndrome, were related to adverse maternal-perinatal outcome. Conclusion: Clinical components of the disease such as lupus nephritis, antiphospholipid syndrome, cardiovascular and mucosal involvement, are factors that may predispose these patients to adverse maternal and/or perinatal outcomes, such as hypertensive disorders associated with pregnancy, low birth weight, preterm, fetal growth restriction, among others(AU)
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Humanos , Feminino , Gravidez , Adolescente , Adulto , Complicações na Gravidez , Artrite/etiologia , Doenças Autoimunes , Hipertensão Induzida pela Gravidez , Lúpus Eritematoso Sistêmico/complicações , Transtornos de Fotossensibilidade/etiologia , Recém-Nascido de Baixo Peso , Recém-Nascido Prematuro , GestantesRESUMO
After menstruation the uterine spiral arteries are repaired through angiogenesis. This process is tightly regulated by the paracrine communication between endometrial stromal cells (EnSCs) and endothelial cells. Any molecular aberration in these processes can lead to complications in pregnancy including miscarriage or preeclampsia (PE). Placental growth factor (PlGF) is a known contributing factor for pathological angiogenesis but the mechanisms remain poorly understood. In this study, we investigated whether PlGF contributes to pathological uterine angiogenesis by disrupting EnSCs and endothelial paracrine communication. We observed that PlGF mediates a tonicity-independent activation of nuclear factor of activated T cells 5 (NFAT5) in EnSCs. NFAT5 activated downstream targets including SGK1, HIF-1α and VEGF-A. In depth characterization of PlGF - conditioned medium (CM) from EnSCs using mass spectrometry and ELISA methods revealed low VEGF-A and an abundance of extracellular matrix organization associated proteins. Secreted factors in PlGF-CM impeded normal angiogenic cues in endothelial cells (HUVECs) by downregulating Notch-VEGF signaling. Interestingly, PlGF-CM failed to support human placental (BeWo) cell invasion through HUVEC monolayer. Inhibition of SGK1 in EnSCs improved angiogenic effects in HUVECs and promoted BeWo invasion, revealing SGK1 as a key intermediate player modulating PlGF mediated anti-angiogenic signaling. Taken together, perturbed PlGF-NFAT5-SGK1 signaling in the endometrium can contribute to pathological uterine angiogenesis by negatively regulating EnSCs-endothelial crosstalk resulting in poor quality vessels in the uterine microenvironment. Taken together the signaling may impact on normal trophoblast invasion and thus placentation and, may be associated with an increased risk of complications such as PE.
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Endométrio , Neovascularização Patológica , Fator de Crescimento Placentário , Pré-Eclâmpsia , Proteínas Serina-Treonina Quinases , Fatores de Transcrição , Feminino , Humanos , Gravidez , Endométrio/metabolismo , Endométrio/irrigação sanguínea , Ensaio de Imunoadsorção Enzimática , Proteínas Imediatamente Precoces/metabolismo , Neovascularização Patológica/metabolismo , Fator de Crescimento Placentário/metabolismo , Pré-Eclâmpsia/metabolismo , Pré-Eclâmpsia/fisiopatologia , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais , Células Estromais/metabolismo , Fatores de Transcrição/metabolismoRESUMO
The placenta plays an essential role in pregnancy, leading to proper fetal development and growth. As an organ with multiple physiological functions for both mother and fetus, it is a highly energetic and metabolically demanding tissue. Mitochondrial physiology plays a crucial role in the metabolism of this organ and thus any alteration leading to mitochondrial dysfunction has a severe outcome in the development of the fetus. Pregnancy-related pathological states with a mitochondrial dysfunction outcome include preeclampsia and gestational diabetes mellitus. In this review, we address the role of mitochondrial morphology, metabolism and physiology of the placenta during pregnancy, highlighting the roles of the cytotrophoblast and syncytiotrophoblast. We also describe the relationship between preeclampsia, gestational diabetes, gestational diabesity and pre-pregnancy maternal obesity with mitochondrial dysfunction.
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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.
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The emergence of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to the global COVID-19 pandemic, significantly impacting the health of pregnant women. Obstetric populations, already vulnerable, face increased morbidity and mortality related to COVID-19, aggravated by preexisting comorbidities. Recent studies have shed light on the potential correlation between COVID-19 and preeclampsia (PE), a leading cause of maternal and perinatal morbidity worldwide, emphasizing the significance of exploring the relationship between these two conditions. Here, we review the pathophysiological similarities that PE shares with COVID-19, with a particular focus on severe COVID-19 cases and in PE-like syndrome cases related with SARS-CoV-2 infection. We highlight cellular and molecular mechanistic inter-connectivity between these two conditions, for example, regulation of renin-angiotensin system, tight junction and barrier integrity, and the complement system. Finally, we discuss how COVID-19 pandemic dynamics, including the emergence of variants and vaccination efforts, has shaped the clinical scenario and influenced the severity and management of both COVID-19 and PE. Continued research on the mechanisms of SARS-CoV-2 infection during pregnancy and the potential risk of developing PE from previous infections is warranted to delineate the complexities of COVID-19 and PE interactions and to improve clinical management of both conditions.
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COVID-19 , Pré-Eclâmpsia , Complicações Infecciosas na Gravidez , SARS-CoV-2 , Humanos , COVID-19/fisiopatologia , COVID-19/imunologia , Gravidez , Feminino , Pré-Eclâmpsia/fisiopatologia , Pré-Eclâmpsia/epidemiologia , Pré-Eclâmpsia/imunologia , SARS-CoV-2/fisiologia , Complicações Infecciosas na Gravidez/imunologia , Complicações Infecciosas na Gravidez/virologia , Sistema Renina-AngiotensinaRESUMO
OBJECTIVE: To explore the association between serum levels and food intake of Vitamin D (VD) among healthy women in mid-pregnancy and preeclampsia. STUDY DESIGN: In a Brazilian multicentre cohort of healthy nulliparous pregnant women from five maternity centres we developed a nested case-control analysis comparing cases with and without preeclampsia. Women were enrolled and followed during prenatal care, including only singleton pregnancies, without any fetal malformations or previous chronic maternal disease. We matched 87 cases of preeclampsia to eligible controls randomly selected in a 1:1 ratio, by age and region. MAIN OUTCOME MEASURES: Blood samples from these were collected, and a 24-hour recall of food intake was obtained in mid-pregnancy, between 19 and 21 weeks. VD serum levels (25-hydroxyvitamin D) were measured by liquid chromatography-tandem mass spectrometry and were categorized as deficient, insufficient, and sufficient. The dietary intake of VD was estimated with the 24-hour diet recall applied at the same time and from supplementation. Maternal characteristics and VD levels were compared between cases and controls with OR and respective 95 %CI. Multivariate analysis using the Path method was used to assess relationships among VD, PE, BMI, skin colour/ethnicity, and diet. RESULTS: The maternal characteristics of both groups were similar, except for the higher occurrence of obesity among women with preeclampsia (OR 3.47, 95 %CI 1.48-8.65). Dietary intake of VD was similar in both groups, and most of the women in both groups consumed insufficient VD (82.2 vs 79.3 % in the groups with and without PE). CONCLUSIONS: Levels and dietary intake of VD were not associated with PE in this Brazilian sample of healthy pregnant women; however, BMI and skin colour/ethnicity were associated with PE.
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Pré-Eclâmpsia , Segundo Trimestre da Gravidez , Vitamina D , Humanos , Feminino , Gravidez , Pré-Eclâmpsia/sangue , Adulto , Brasil/epidemiologia , Vitamina D/sangue , Vitamina D/análogos & derivados , Vitamina D/administração & dosagem , Estudos de Casos e Controles , Segundo Trimestre da Gravidez/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/epidemiologia , Adulto JovemRESUMO
Preeclampsia (PE) is a life-threatening pregnancy-specific complication with controversial mechanisms and no effective treatment except delivery is available. Currently, increasing researchers suggested that PE shares pathophysiologic features with protein misfolding/aggregation disorders, such as Alzheimer disease (AD). Evidences have proposed defective autophagy as a potential source of protein aggregation in PE. Endoplasmic reticulum-selective autophagy (ER-phagy) plays a critical role in clearing misfolded proteins and maintaining ER homeostasis. However, its roles in the molecular pathology of PE remain unclear. We found that lncRNA DUXAP8 was upregulated in preeclamptic placentae and significantly correlated with clinical indicators. DUXAP8 specifically binds to PCBP2 and inhibits its ubiquitination-mediated degradation, and decreased levels of PCBP2 reversed the activation effect of DUXAP8 overexpression on AKT/mTOR signaling pathway. Function experiments showed that DUXAP8 overexpression inhibited trophoblastic proliferation, migration, and invasion of HTR-8/SVneo and JAR cells. Moreover, pathological accumulation of swollen and lytic ER (endoplasmic reticulum) was observed in DUXAP8-overexpressed HTR8/SVneo cells and PE placental villus trophoblast cells, which suggesting that ER clearance ability is impaired. Further studies found that DUXAP8 overexpression impaired ER-phagy and caused protein aggregation medicated by reduced FAM134B and LC3II expression (key proteins involved in ER-phagy) via activating AKT/mTOR signaling pathway. The increased level of FAM134B significantly reversed the inhibitory effect of DUXAP8 overexpression on the proliferation, migration, and invasion of trophoblasts. In vivo, DUXAP8 overexpression through tail vein injection of adenovirus induced PE-like phenotypes in pregnant rats accompanied with activated AKT/mTOR signaling, decreased expression of FAM134B and LC3-II proteins and increased protein aggregation in placental tissues. Our study reveals the important role of lncRNA DUXAP8 in regulating trophoblast biological behaviors through FAM134B-mediated ER-phagy, providing a new theoretical basis for understanding the pathogenesis of PE.
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Autofagia , Retículo Endoplasmático , Pré-Eclâmpsia , Proteínas Proto-Oncogênicas c-akt , RNA Longo não Codificante , Transdução de Sinais , Serina-Treonina Quinases TOR , Trofoblastos , Adulto , Animais , Feminino , Humanos , Gravidez , Ratos , Autofagia/genética , Linhagem Celular , Movimento Celular/genética , Proliferação de Células/genética , Retículo Endoplasmático/metabolismo , Placenta/metabolismo , Pré-Eclâmpsia/metabolismo , Pré-Eclâmpsia/genética , Pré-Eclâmpsia/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Serina-Treonina Quinases TOR/metabolismo , Trofoblastos/metabolismo , Trofoblastos/patologia , MasculinoRESUMO
Preeclampsia (PE) is a multifactorial pregnancy disorder characterized by hypertension and proteinuria, posing significant risks to both maternal and fetal health. Despite extensive research, its complex pathophysiology remains incompletely understood. This narrative review aims to elucidate the intricate mechanisms contributing to PE, focusing on abnormal placentation, maternal systemic response, oxidative stress, inflammation, and genetic and epigenetic factors. This review synthesizes findings from recent studies, clinical trials, and meta-analyses, highlighting key molecular and cellular pathways involved in PE. The review integrates data on oxidative stress biomarkers, angiogenic factors, immune interactions, and mitochondrial dysfunction. PE is initiated by poor placentation due to inadequate trophoblast invasion and improper spiral artery remodeling, leading to placental hypoxia. This triggers the release of anti-angiogenic factors such as soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng), causing widespread endothelial dysfunction and systemic inflammation. Oxidative stress, mitochondrial abnormalities, and immune dysregulation further exacerbate the condition. Genetic and epigenetic modifications, including polymorphisms in the Fms-like tyrosine kinase 1 (FLT1) gene and altered microRNA (miRNA) expression, play critical roles. Emerging therapeutic strategies targeting oxidative stress, inflammation, angiogenesis, and specific molecular pathways like the heme oxygenase-1/carbon monoxide (HO-1/CO) and cystathionine gamma-lyase/hydrogen sulfide (CSE/H2S) pathways show promise in mitigating preeclampsia's effects. PE is a complex disorder with multifactorial origins involving abnormal placentation, endothelial dysfunction, systemic inflammation, and oxidative stress. Despite advances in understanding its pathophysiology, effective prevention and treatment strategies remain limited. Continued research is essential to develop targeted therapies that can improve outcomes for both mothers and their babies.