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Etiology and Pathophysiologic Mechanisms of PE21
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Objective: Preeclampsia (PE) is a multi-systemic complication of pregnancy often characterised with the
onset of hypertension and proteinuria after 20 weeks of gestation. Today, PE is the leading cause of
maternal and perinatal morbidity and mortality worldwide. An early detection of PE would allow a chance
to plan the appropriate monitoring and fo...
Contexts in source publication
Context 1
... is considered to be a complex interaction between placental factors, maternal constitutional factors and immunological as well as vascular changes due to pregnancy resulting in the characteristic hypertension and proteinuria. Several pathophysiological mechanisms have been implicated in the pathogenesis of PE, however currently the mechanisms involved behind this disease still remains incompletely elucidated which complicates the prediction and treatment of PE (18-2) (Figure 1). ...
Context 2
... is considered to be a complex interaction between placental factors, maternal constitutional factors and immunological as well as vascular changes due to pregnancy resulting in the characteristic hypertension and proteinuria. Several pathophysiological mechanisms have been implicated in the pathogenesis of PE, however currently the mechanisms involved behind this disease still remains incompletely elucidated which complicates the prediction and treatment of PE (18-2) (Figure 1). ...
Similar publications
Introduction: Preeclampsia is a medical condition characterized by hypertension and proteinuria during pregnancy, with the symptoms generally manifesting in the 3rd trimester. Hypertension brings hemodynamic changes; it is therefore expected that arterial blood flow velocity waveforms will be different in the uterine and ophthalmic arteries in pree...
Citations
... Peningkatan konsentrasi sFlt-1 yang bersirkulasi akan menurunkan konsentrasi PlGF (Spradley et al., 2016;Lecarpentier et al., 2020;Yeni et al., 2020). PlGF memiliki peran penting dalam angiogenesis fisiologis yang diperlukan dalam perkembangan vaskular plasenta dan bersikap protektif dengan mencegah kerusakan oksidatif yang disebabkan oleh hipoksia (Felicia Sunjaya dan Paulo Sunjaya, 2019;Wang Du dan Jiang, 2021). ...
Hypertension in pregnancy is one of the causes of morbidity and mortality in mothers and babies. PlGF has been shown to be associated with the diagnosis of hypertensive disorders in pregnancy. Pregnant women with hypertension are characterized by reduced circulating PlGF levels, even before clinical signs and symptoms. A decrease in the amount of PlGF is positively correlated with the severity of disease progression This study aimed to analyze the relationship between PlGF levels and blood pressure in pregnant women with hypertension. Observational analytic with cross sectional study design. Sampling was total sampling. The number of subject were 34 peoples. The results showed that there was no significant correlation between PlGF levels and blood pressure in pregnant women with hypertension. PlGF levels have no relationship with blood pressure.
... Preeclampsia is a complication of pregnancy and affects 2-8% of pregnant women and contributes to 14% of total maternal deaths. (Steegers et al. 2010;Lo et al. 2013;Mol et al. 2016;Sunjaya and Sunjaya 2019) Early-onset preeclampsia accounts for one-fifth of preeclampsia cases with severe complications and high mortality. Pathological changes in preeclampsia well precede the onset of clinical manifestations, rendering early diagnosis and intervention nearly impossible. ...
Background
In the current study, we sought to characterise the methylation haplotypes and nucleosome positioning patterns of placental DNA and plasma cell-free DNA of pregnant women with early-onset preeclampsia using whole genome bisulphite sequencing (WGBS) and methylation capture bisulphite sequencing (MCBS) and further develop and examine the diagnostic performance of a generalised linear model (GLM) by incorporating the epigenetic features for early-onset preeclampsia.
Methods
This case-control study recruited pregnant women aged at least 18 years who delivered their babies at our Hospital. In addition, non-pregnant women with no previous history of diseases were included. Placental samples of the villous parenchyma were taken at the time of delivery and venous blood was drawn from pregnant women during non-invasive prenatal testing at 12–15 weeks of pregnancy and nonpregnant women during the physical check-up. WGBS and MCBS were carried out of extracted genomic DNA. Then, we established the GLM by incorporating preeclampsia-specific methylation haplotypes and nucleosome positioning patterns and examined the diagnostic performance of the model by receiver operating characteristic (ROC) curve analysis.
Results
The study included 135 pregnant women and 50 non-pregnant women. Our high-depth MCBS revealed notably different DNA methylation and nucleosome positioning patterns between women with and without preeclampsia. Preeclampsia-specific hypermethylated sites were found predominantly in the promoter regions and particularly enriched in CTCF on the X chromosome. Totally, 2379 preeclampsia-specific methylation haplotypes were found across the entire genome. ROC analysis showed that the area under the ROC curve (AUC) was 0.938 (95%CI 0.877, 1.000). At a GLM cut-off of 0.341, the AUC was the maximum, with a sensitivity of 95.6% and a specificity of 89.7%.
Conclusion
Pregnant women with early-onset preeclampsia exhibit DNA methylation and nucleosome positioning patterns in placental and plasma DNA.
... The basic pathophysiology of PIH and PE is almost the same, resulting from incomplete placentation of spiral arterioles, defective trophoblastic invasion resulting in placental ischemia. This ischemic placenta is responsible for the release of Activin A and Inhibin A [4,5]. Currently there are no specific chemical biomarkers which can help us to diagnose patients of PIH and PE in early stages. ...
Objective: The objective of this study was to compare the levels of Serum Activin A and Inhibin A in Pregnancy induced hypertension, Preeclampsia & Normal Pregnancy Material and Methods: An analytical, cross-sectional study conducted at Chemical Pathology Laboratory Collaborating with Gynae/Obstetric Department of Pakistan Railway Teaching Hospital, Rawalpindi over the period of one year (18 Sep 2019 to 18 March 2020). The study started after the approval of Ethical Review Committee, Riphah International University Islamabad. The sample size was calculated using WHO sample size calculator. Taking Prevalence of PIH and PE is 8%.3 Non probability convenient sampling technique was used. An overall 100 pregnant women with gestation of 20 – 25 weeks, were included. Patients of UTI, Carcinomas, Diabetes Mellitus and other chronic disorders were not included. The subjects were divided into three groups. Group I PIH: This group included 30 pregnant women of PIH; 20 - 25 weeks of gestation, BP: ≥140/90 mmHg on two separate occasions without proteinuria. Group II PE: This group included 20 pregnant women of preeclampsia; 20 - 25 weeks of gestation, BP: ≥140/90 mmHg on two separate occasions with proteinuria (>0.3 g protein/24 hours Urine). Group III Control Group: This group included 50 pregnant women with gestational age of 20 – 25 weeks without any complication as healthy controls. Results: It was determined that Serum Activin A and Serum Inhibin A levels were significantly increased in PIH and PE groups as compared to healthy group. Mean of Serum Activin A in PIH, PE and Control group was (251.53+200.23 pg/ml), (466.95 + 237.40 pg/ml) and (43.35 + 85.22 pg/ml) respectively. Similarly Mean and Standard Deviation of Serum Inhibin A levels in PIH, PE and Control group was (194.78 + 173.00 pg/ml), (349.20 + 190.30 pg/ml) and (17.27 + 44.33 pg/ml) respectively. One-way ANOVA and post-hoc Tukey analysis was conducted to compare the mean of Serum Activin A and Serum Inhibin A levels among three different groups i.e Group 1(PIH and PE), Group 2(PIH and Control) and Group 3 (PE and Control). p-value< 0.05 was considered as statistically significant. Conclusion: It can be concluded that Serum Activin A and Serum Inhibin A can be used as biochemical markers of PIH and PE. Estimation of Serum Activin A and Inhibin A at an early stage can detect PIH and PE early and further prevents their complications such as Eclampsia and HELLP syndrome. Keywords: Pregnancy induced hypertension (PIH), Pre-eclampsia (PE), HELLP syndrome (H – Hemolysis, EL- Elevated Liver Enzymes, LP – Low platelets count), Serum activin A, Serum inhibin A.
... These include body mass index, mean arterial pressure, parity scoring, assessment of ultrasound-guided uterine artery pulsatility index, and serum biochemical markers (serum pregnancy-associated plasma protein-A and placental growth factor). [5][6][7]12 Nevertheless, these tools have not reached the mainstream in low-and middleincome countries, in part because of their lower specificity or higher cost. It was therefore imperative to develop a cheap, yet simple and handy tool that could predict the adverse outcomes of preeclampsia with higher accuracy. ...
Objective
To determine the predicted probability percentage of complications in women with pre‐eclampsia using the Pre‐eclampsia Integrated Estimate of Risk (fullPIERS) model within the first 24 h after admission and assess the model's predictive value for complications of pre‐eclampsia.
Methods
This was a prospective cohort study in which the fullPIERS model was applied to 256 pregnant women with pre‐eclampsia within the first 24 h after admission. These women were then followed for 48 h to 7 days for maternal and fetal complications. Reciever operating characteristics (ROC) curves were generated to assess the performance of the fullPIERS model for adverse outcomes of pre‐eclampsia.
Results
Of the 256 women enrolled in the study, 101 women (39.5%) developed maternal complications, 120 women (46.9%) developed fetal complications, and 159 women (62.1%) developed both. With an area under the ROC curve of 0.843 (95% confidence interval 0.789–0.897), the fullPIERS model had good discriminating ability to predict complications at any time point between 48 h and 7 days after admission. The sensitivity and specificity of the model at a ≥5.9% cut‐off value for predicting adverse maternal outcomes were 60% and 97%, respectively; they were 44% and 96%, respectively, for predicting combined fetomaternal complications with a cut‐off value of 4.9%.
Conclusions
The fullPIERS model performs reasonably well in predicting adverse maternal and fetal outcomes in women with pre‐eclampsia.
... Hypertension, proteinuria, and edema due to PE are all caused by cytotoxic factors [8,26]. In pregnant women with PE, the activation of vascular endothelial cells caused by inflammation and placental abnormalities can lead to changes in the levels of various peripheral blood markers, some of which are altered earlier than the appearance of clinical symptoms [6,[27][28][29]. Oxidative stress in the placenta induces the release of placental factors into the maternal blood flow that further triggers endothelial dysfunction and enhanced vascular permeability. ...
Introduction
As a leading cause of pregnancy and fetal mortality, pre-eclampsia impacts about 5–8% of pregnancies globally. To date, few studies have focused on the role played by (NOD)-like receptors protein 3 (NLRP3) in peripheral blood in early-onset pre-eclampsia (PE). In this study, we investigated whether NLRP3 expression in monocytes before 20 weeks of gestation was associated with an increased risk of early-onset PE.
Methodology
During the study period from 2019 to 2021, women with singleton pregnancies were enrolled in this prospective study at the General Hospital of Northern Theater Command. A generalized additive model (GAM) and logistic regression models were applied to determine any association between NLRP3 and the risk of early-onset PE.
Results
In total, 571 and 48 subjects were included in the control and pre-eclampsia groups, respectively. The GAM and logistic regression models showed that NLRP3 was a significant factor for PE occurrence. The area under the curve, accuracy, specificity, sensitivity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.86, 0.82, 0.95, 0.72, 15.17, 0.29, and 52.0, respectively.
Conclusion
The monitoring for NLRP3 in peripheral blood may be a potential, prospectively identifying risk factor for preeclampsia.
... Esta iniciativa tem o propósito de identificar biomarcadores de fácil mensuração, baixo custo e que possuam nível de sensibilidade ideal (>90%), a fim de garantir a fidedignidade na previsão do risco e/ou gravidade da PE, incluindo tanto os desfechos maternos, quanto perinatais, de forma a complementar a semiologia clínica e o doppler das artérias uterinas, que avalia o comprometimento da circulação uteroplacetária (UYAR et al., 2015). Dentre estes biomarcadores, o peptídio natriurético cerebral (PNC), citocinas próinflamatórias, endoglina solúvel, fator de crescimento placentário (FCPl), tirosina quinase-1 solúvel tipo fms (sFlt-1), fator de crescimento endotelial vascular (VEGF), proteína plasmática A-2 associado à gravidez (PAPPA2), fibronectina glicosilada (GlyFn), ferritina, vasopressina, copeptina, cálcio e ácido úrico parecem possuir relação com a PE (KUMAR et al., 2019;PAULA et al., 2019;UYAR et al., 2015;HUHN et al., 2020;SUNJAYA et al., 2019;KAT et al., 2019; HULUTA et al., 2018; SILVA et al.,2020;MENDONÇA et al., 2022). Entretanto, diante destes marcadores, o ácido úrico merece atenção, principalmente devido sua simplicidade de mensuração e interpretação, podendo ser inserido na prática clínica mais facilmente(KUMAR et al., 2019;PAULA et al., 2019). ...
A primeira edição do Congresso Brasileiro de Saúde da Criança e do Adolescente foi realizado de forma remota, nos dias 16, 17 e 18 de dezembro de 2022, sendo promovido pelo Instituto Academic (CNPJ: 42.698.982/0001-87). O evento contou com a participação de vários palestrantes renomados que discutiram temáticas relevantes sobre o cuidado à saúde da criança e adolescente. O objetivo do evento foi de promover a educação, capacitação, treinamento e atualização multidisciplinar na área da saúde da criança e do adolescente, sendo destinado a discentes, docentes, profissionais de saúde e demais interessados pela discussão da temática. O e-book é composto por 50 capítulos que servem de base para a construção do conhecimento baseado em evidências, servindo de base para reflexão, discussão e embasamento teórico para a construção de outros estudos sobre a área.
... La β-gonadotrophine chorionique humaine (β-hCG) est un promoteur de la croissance et de la différenciation cellulaire dans l'embryon sécrété par les cellules syncytiotrophoblastiques du placenta avec la fonction principale de maintenir l'apport vasculaire du placenta pendant la grossesse. Dans les grossesses normales, ses niveaux augmentent jusqu'à 9 à 10 semaines, a une probabilité prédictive de 91 % de la pré-éclampsie [41]. L'étude conclut que des taux sériques élevés de β-hCG chez les femmes enceintes au deuxième trimestre indiquent un risque accru d'hypertension gestationnelle et de prééclampsie et que des taux élevés de β-hCG sont associés à la gravité de la maladie [44]. ...
L'étude des marqueurs biologiques de la pré-éclampsie est une approche de recherche qui jette les bases d'un dépistage précoce, d'un suivi et d'un pronostic. Certes, pour une maladie ayant un impact aussi important sur la morbi-mortalité maternelle et périnatale, la mise en place de ces indicateurs biologiques permettrait d'alléger la charge des patientes et du personnel soignant. L'objectif de cette revue était de présenter les biomarqueurs de la pré-éclampsie actuellement à l'étude dans le monde en vue d'ouvrir ce champ aux études locales. Une revue narrative de la littérature a été menée dans Google Scholar et Pubmed et a procédé en sélectionnant des revues systématiques, des méta-analyses ou des études comparatives bien menées sur ce sujet au cours des cinq dernières années. Les séries de cas ou les cas cliniques n'ont pas été retenus. Il en est ressorti que les marqueurs angiogéniques dont le sFlt-1, le P1GF, le soluble endogline et PAPP sont les plus étudiés dans les pays industrialisés. Cependant d'autres marqueurs sont également étudiés, notamment des marqueurs hématologiques (Le ratio Neutrophil-Lymphocyte, l'Hématocrite et l'Indice de distribution des globules rouges), biochimiques (la Ferritine, l'Acide urique et la Protéine C Réactive) ou hormonaux (La β-Hormone Chorionique Gonadotrope et l'OEstradiol). En outre, l'étude des marqueurs est moins développée dans les pays à faibles ressources. Cette revue montre que plusieurs marqueurs angiogéniques, hématologiques, biochimiques et hormonaux peuvent être étudiés dans ce domaine qui semble vierge dans notre environnement.
... The proliferation and migration of endothelial cells as well as vascular permeability are influenced by a number of angiogenicrelated molecules, including PlGF, a proangiogenic member of the VEGF family. Placental dysfunction is more likely to emerge when pro-and antiangiogenic forces are out of balance [19] . Studies done during the second trimester show that blood pressure monitoring is a useful screening technique for the emergence of PE. ...
... 8 Preterm birth, intrauterine growth restriction (IUGR), preeclampsia, and placental separation have all been linked to an increase in maternal serum alpha-fetoprotein (MSAFP). 9 These lesions allow alpha-fetoprotein to leak from the high-concentration foetal circulation to the lowconcentration maternal circulation, resulting in an increase in maternal serum AFP. It has also been linked to uterine deformity in women. ...
... Main risk factors associated to PE includes genetic background (family history) or previous events of PE; preexisting medical conditions, like hypertension, antiphospholipid syndrome, or insulin-dependent diabetes; obesity; age (≥40 years old), assisted reproductive techniques; nulliparity and multiparity (Lisonkova and Joseph, 2013;Paré et al., 2014). In this context and, in the absence of effective therapies, early prediction of PE is critical for preventive therapy and to guarantee adequate patient surveillance (Wagner, 2004;Sibai, 2005;Sunjaya et al., 2019). Likewise, a detailed understanding of the pathophysiology of PE will help to find novel biomarkers with translational applications. ...
The human placenta is a critical structure with multiple roles in pregnancy, including fetal nutrition and support, immunological, mechanical and chemical barrier as well as an endocrine activity. Besides, a growing body of evidence highlight the relevance of this organ on the maternofetal wellbeing not only during gestation, but also from birth onwards. Extracellular vesicles (EVs) are complex macromolecular structures of different size and content, acting as carriers of a diverse set of molecules and information from donor to recipient cells. Since its early development, the production and function of placental-derived EVs are essential to ensure an adequate progress of pregnancy. In turn, the fetus receives and produce their own EVs, highlighting the importance of these components in the maternofetal communication. Moreover, several studies have shown the clinical relevance of EVs in different obstetric pathologies such as preeclampsia, infectious diseases or gestational diabetes, among others, suggesting that they could be used as pathophysiological biomarkers of these diseases. Overall, the aim of this article is to present an updated review of the published basic and translational knowledge focusing on the role of placental-derived EVs in normal and pathological pregnancies. We suggest as well future lines of research to take in this novel and promising field.
