4-Hydroxyglutamate is a novel predictor of pre-eclampsia.
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ABSTRACT:
SUBMITTER: Sovio U
PROVIDER: S-EPMC7124498 | biostudies-literature | 2020 Feb
REPOSITORIES: biostudies-literature
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4-Hydroxyglutamate is a novel predictor of pre-eclampsia.
Sovio Ulla U McBride Nancy N Wood Angela M AM Masconi Katya L KL Cook Emma E Gaccioli Francesca F Charnock-Jones D Stephen DS Lawlor Debbie A DA Smith Gordon C S GCS
International journal of epidemiology 20200201 1
<h4>Background</h4>Pre-term pre-eclampsia is a major cause of maternal and perinatal morbidity and mortality worldwide. A multi-centre randomized-controlled trial has shown that first-trimester screening followed by treatment of high-risk women with aspirin reduces the risk of pre-term pre-eclampsia. However, the biomarkers currently employed in risk prediction are only weakly associated with the outcome.<h4>Methods</h4>We conducted a case-cohort study within the Pregnancy Outcome Prediction stu ...[more]
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Project description:BackgroundProteinuria is one of the essential criteria for the clinical diagnosis of pre-eclampsia. Increasing levels of proteinuria is considered to be associated with adverse maternal and fetal outcomes. We aim to determine the accuracy with which the amount of proteinuria predicts maternal and fetal complications in women with pre-eclampsia by systematic quantitative review of test accuracy studies.MethodsWe conducted electronic searches in MEDLINE (1951 to 2007), EMBASE (1980 to 2007), the Cochrane Library (2007) and the MEDION database to identify relevant articles and hand-search of selected specialist journals and reference lists of articles. There were no language restrictions for any of these searches. Two reviewers independently selected those articles in which the accuracy of proteinuria estimate was evaluated to predict maternal and fetal complications of pre-eclampsia. Data were extracted on study characteristics, quality and accuracy to construct 2 x 2 tables with maternal and fetal complications as reference standards.ResultsSixteen primary articles with a total of 6749 women met the selection criteria with levels of proteinuria estimated by urine dipstick, 24-hour urine proteinuria or urine protein:creatinine ratio as a predictor of complications of pre-eclampsia. All 10 studies predicting maternal outcomes showed that proteinuria is a poor predictor of maternal complications in women with pre-eclampsia. Seventeen studies used laboratory analysis and eight studies bedside analysis to assess the accuracy of proteinuria in predicting fetal and neonatal complications. Summary likelihood ratios of positive and negative tests for the threshold level of 5 g/24 h were 2.0 (95% CI 1.5, 2.7) and 0.53 (95% CI 0.27, 1) for stillbirths, 1.5 (95% CI 0.94, 2.4) and 0.73 (95% CI 0.39, 1.4) for neonatal deaths and 1.5 (95% 1, 2) and 0.78 (95% 0.64, 0.95) for Neonatal Intensive Care Unit admission.ConclusionMeasure of proteinuria is a poor predictor of either maternal or fetal complications in women with pre-eclampsia.
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Project description:The etiology of preeclampsia, a hypertensive disorder of human pregnancy, remains unknown. We addressed fetal sex selection and the suggestive role of fetal HLA-G and related genes, regulating maternal immune responses, in preeclampsia pathogenesis. We assessed birth sex ratios, weights, and seasonality of preeclampsia among 1.79 million births in Finland. We studied haplotypes of HLA-G 3’ untranslated region (UTR), regulating HLA-G expression, in 1000 Genomes series and in a preeclampsia cohort (n=1249). We quantified placental (n=163) mRNA expression of 136 genes, studied HLA-G and IFNα protein expression by immunohistochemistry, and measured maternal and fetal circulating IFNα levels by ELISA. Population-level data showed loss of male fetuses as a characteristic of preeclampsia. As a potential contributor to immune-mediated loss, we found balancing selection at HLA-G 3’UTR modulating sex ratio, and association of HLA-G 3’UTR haplotypes with placental HLA-G expression. HLA-G and its receptors were downregulated in preeclampsia placentas, and surprisingly, interferon alpha-1 (IFNA1) was highly upregulated. IFNA1 and HLA-G distinguished preeclampsia better than placental FLT1 expression. Fetal but not maternal circulating IFNα, produced by trophoblasts, showed association with maternal hypertension and fetal growth restriction. We uncover the link between placental HLA-G expression and human birth sex ratio. We propose that preeclampsia shares, through reduced HLA-G mediated immunotolerance, the mechanism needed to fight placental viral infections and malaria in evolution. IFNα upregulation in preeclampsia placenta, together with its known actions upstream of inflammatory genes, encourages testing IFNα inhibitors and especially the pregnancy-approved antimalarial hydroxichloroquine in treatment of preeclampsia.
2019-11-25 | GSE125460 | GEO
Project description:BackgroundPre-eclampsia is the most common complication occurring during pregnancy. In the majority of cases, it is concurrent with other pathologies in a comorbid manner (frequent co-occurrences in patients), such as diabetes mellitus, gestational diabetes and obesity. Providing bronchial asthma, pulmonary tuberculosis, certain neurodegenerative diseases and cancers as examples, we have shown previously that pairs of inversely comorbid pathologies (rare co-occurrences in patients) are more closely related to each other at the molecular genetic level compared with randomly generated pairs of diseases. Data in the literature concerning the causes of pre-eclampsia are abundant. However, the key mechanisms triggering this disease that are initiated by other pathological processes are thus far unknown. The aim of this work was to analyse the characteristic features of genetic networks that describe interactions between comorbid diseases, using pre-eclampsia as a case in point.ResultsThe use of ANDSystem, Pathway Studio and STRING computer tools based on text-mining and database-mining approaches allowed us to reconstruct associative networks, representing molecular genetic interactions between genes, associated concurrently with comorbid disease pairs, including pre-eclampsia, diabetes mellitus, gestational diabetes and obesity. It was found that these associative networks statistically differed in the number of genes and interactions between them from those built for randomly chosen pairs of diseases. The associative network connecting all four diseases was composed of 16 genes (PLAT, ADIPOQ, ADRB3, LEPR, HP, TGFB1, TNFA, INS, CRP, CSRP1, IGFBP1, MBL2, ACE, ESR1, SHBG, ADA). Such an analysis allowed us to reveal differential gene risk factors for these diseases, and to propose certain, most probable, theoretical mechanisms of pre-eclampsia development in pregnant women. The mechanisms may include the following pathways: [TGFB1 or TNFA]-[IL1B]-[pre-eclampsia]; [TNFA or INS]-[NOS3]-[pre-eclampsia]; [INS]-[HSPA4 or CLU]-[pre-eclampsia]; [ACE]-[MTHFR]-[pre-eclampsia].ConclusionsFor pre-eclampsia, diabetes mellitus, gestational diabetes and obesity, we showed that the size and connectivity of the associative molecular genetic networks, which describe interactions between comorbid diseases, statistically exceeded the size and connectivity of those built for randomly chosen pairs of diseases. Recently, we have shown a similar result for inversely comorbid diseases. This suggests that comorbid and inversely comorbid diseases have common features concerning structural organization of associative molecular genetic networks.
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Project description:Background:The etiology and pathogenesis of pre-eclampsia (PE) is unclear, and there is no ideal early clinical biomarker for prediction of PE. The competing endogenous RNA (ceRNA) hypothesis is a new approach to uncover the molecular pathology of PE. The first aim of this study was to perform messenger RNA, long non-coding RNA, and circular RNA (circRNA) expression profiling of human normal and severe pre-eclampsia (SPE) placentas. circRNA, which has a stable structure, is a more suitable biomarker than other types of RNA. Therefore, the second aim of our study was to select some differentially expressed circRNAs in PE placentas as early clinical biomarkers of PE in blood circulation. Results:Using microarray analysis, we investigated differentially expressed ceRNAs in human normal and SPE placentas. Bioinformatics, such as gene ontology, KEGG pathway, and ceRNA network analyses, were performed to evaluate the microarray data and gain further insights into the biological processes. RNAs (Chd5, Furin, lnc-ELAVL4-9:1, lnc-RAP1GAP2-5:2, hsa_circ_0036877, hsa_circ_0036878, hsa_circ_0055724, hsa_circ_0049730, and hsa_circ_0036474) were validated by quantitative real-time PCR (qRT-PCR). RNA immunoprecipitation (RIP) of AGO2 in htra-8 cells and qRT-PCR analysis of hsa_circ_0036877 expression in maternal whole peripheral blood samples of participants were then conducted to confirm that hsa_circ_0036877 is a ceRNA and potential novel blood biomarker for early PE, respectively. Conclusion:Our study is the first systematic profiling of ceRNAs in placentas of PE patients and revealed the global ceRNA network integration in PE. Moreover, hsa_circ_0036877 can function as a ceRNA and serve as a potential novel blood biomarker for early PE.
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Project description:Introduction:Pre-eclampsia is a hypertensive disorder in pregnancy. Maternal sequelae that may occur include impaired liver function, disseminated intravascular coagulation, seizures (eclampsia), stroke, and death. Thus, providers should know how to recognize (diagnose) and treat pre-eclampsia and eclampsia. Methods:A simulator with noninvasive blood pressure monitoring was used. Transducers for fetal heart rate and contraction monitoring were placed on the simulator, which represented the patient. After obtaining a history and performing a physical examination, resident physician (postgraduate years 1-4) and nurse learners had to diagnose pre-eclampsia and treat this condition. They also had to treat severe-range blood pressures and manage eclampsia. Learner performance was assessed with a checklist. Debriefing followed the simulation. Results:Thirty resident learners participated in the study. Nurses did not participate. All resident learners indicated familiarity with the diagnosis and management of pre-eclampsia and emergent hypertension and managed these conditions correctly. All resident learners reported not being confident in managing eclampsia. None of the learners were able to stop the eclamptic seizure. All resident learners were more confident in managing eclampsia after the scenario compared with before (mean confidence level 3.6 ± 0.5 vs. 1.1 ± 0.4, p < .001). Discussion:Resident learners were familiar with the management of pre-eclampsia and emergent hypertension but not with eclampsia. We recommend that eclampsia simulations occur in a laboratory and in situ on the labor and delivery floor with interprofessional team members including obstetricians, nurses, anesthesiologists, emergency and family medicine physicians, nurse practitioners, and physician assistants.
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Project description:Sub-Saharan Africa has the highest maternal mortality ratio at 500 deaths per 100,000 live births. In Mozambique maternal mortality is estimated at 249-480 per 100,000 live births and eclampsia is the third leading cause of death. The objective of this study was to describe the community understanding of pre-eclampsia and eclampsia, as a crucial step to improve maternal and perinatal health in southern Mozambique.This qualitative study was conducted in Maputo and Gaza Provinces of southern Mozambique. Twenty focus groups were convened with pregnant women, partners and husbands, matrons and traditional birth attendants, and mothers and mothers-in-law. In addition, ten interviews were conducted with traditional healers, matrons, and a traditional birth attendant. All discussions were audio-recorded, translated from local language (Changana) to Portuguese and transcribed verbatim prior to analysis with QSR NVivo 10. A thematic analysis approach was taken.The conditions of "pre-eclampsia" and "eclampsia" were not known in these communities; however, participants were familiar with hypertension and seizures in pregnancy. Terms linked with the biomedical concept of pre-eclampsia were high blood pressure, fainting disease and illness of the heart, whereas illness of the moon, snake illness, falling disease, childhood illness, illness of scaresand epilepsy were used to characterizeeclampsia. The causes of hypertension in pregnancy were thought to include mistreatment by in-laws, marital problems, and excessive worrying. Seizures in pregnancy were believed to be caused by a snake living inside the woman's body. Warning signs thought to be common to both conditions were headache, chest pain, weakness, dizziness, fainting, sweating, and swollen feet.Local beliefs in southern Mozambique, regarding the causes, presentation, outcomes and treatment of pre-eclampsia and eclampsia were not aligned with the biomedical perspective. The community was often unaware of the link between hypertension and seizures in pregnancy. The numerous widespread myths and misconceptions concerning pre-eclampsia and eclampsiamay induceinappropriatetreatment-seeking and demonstrate a need for increased community education regarding pregnancy and associated complications.NCT01911494.
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Project description:BACKGROUND: An evidence-based strategy exists to reduce maternal morbidity and mortality associated with severe pre-eclampsia/eclampsia (PE/E), but it may be difficult to implement in low-resource settings. This study examines whether facilities that provide emergency obstetric and newborn care (EmONC) in Afghanistan have the capacity to manage severe PE/E cases. METHODS: A further analysis was conducted of the 2009-10 Afghanistan EmONC Needs Assessment. Assessors observed equipment and supplies available, and services provided at 78 of the 127 facilities offering comprehensive EmONC services and interviewed 224 providers. The providers also completed a written case scenario on severe PE/E. Descriptive statistics were used to summarize facility and provider characteristics. Student t-test, one-way ANOVA, and chi-square tests were performed to determine whether there were significant differences between facility types, doctors and midwives, and trained and untrained providers. RESULTS: The median number of severe PE/E cases in the past year was just 5 (range 0-42) at comprehensive health centers (CHCs) and district hospitals, compared with 44 (range 0-130) at provincial hospitals and 108 (range 32-540) at regional and specialized hospitals (p?<?0.001). Most facilities had the drugs and supplies needed to treat severe PE/E, including the preferred anticonvulsant, magnesium sulfate (MgSO4). One-third of the smallest facilities and half of larger facilities reported administering a second-line drug, diazepam, in some cases. In the case scenario, 96% of doctors and 89% of midwives recognized that MgSO4 should be used to manage severe PE/E, but 42% of doctors and 58% of midwives also thought diazepam had a role to play. Providers who were trained on the use of MgSO4 scored significantly higher than untrained providers on six of 20 items in the case scenario. Providers at larger facilities significantly outscored those at smaller facilities on five items. There was a significant difference between doctors and midwives on only one item: continued use of anti-hypertensives after convulsions are controlled. CONCLUSIONS: Drugs and supplies needed to treat severe PE/E are widely available at EmONC facilities in Afghanistan, but providers lack knowledge in some areas, especially concerning the use of MgSO4 and diazepam. Providers who have specialized training or work at larger facilities are better at managing cases of severe PE/E. The findings suggest a need to clarify service delivery guidelines, offer refresher training, and reinforce best practices with supervision and reinforcement.
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Project description:Pre-eclampsia (PE) is a clinical syndrome characterized by new-onset hypertension and proteinuria at ?20 weeks of gestation, and is a leading cause of maternal and perinatal morbidity and mortality. Previous studies have gathered abundant data about PE such as risk factors and pathological findings. However, most of these data are not semantically structured. Clinical data on PE patients are often generated with semantic heterogeneity such as using disparate terminology to describe the same phenomena. In clinical studies, interoperability of heterogenic clinical data is required in various situations. In such a situation, it is necessary to develop an interoperable and standardized semantic framework to research the pathology of PE more comprehensively and to achieve interoperability of heterogenic clinical data of PE patients. In this study, we developed an ontology representing clinical features, treatments, genetic factors, environmental factors, and other aspects of the current knowledge in the domain of PE. We call this pre-eclampsia ontology "PEO". To achieve interoperability with other ontologies, the core structure of PEO was compliant with the hierarchy of the Basic Formal Ontology (BFO). The PEO incorporates a wide range of key concepts and terms of PE from clinical and biomedical research in structuring the knowledge base that is specific to PE; therefore, PEO is expected to enhance PE-specific information retrieval and knowledge discovery in both clinical and biomedical research fields.
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Project description:Pre-eclampsia is a leading cause of maternal and perinatal morbidity and mortality. The burden of disease lies mainly in low-middle income countries. The aim of this project is to establish a pre-eclampsia biobank in South Africa to facilitate research in the field of pre-eclampsia with a focus on phenotyping severe disease.The approach of our biobank is to collect biological specimens, detailed clinical data, tests, and biophysical examinations, including magnetic resonance imaging (MRI) of the brain, MRI of the heart, transcranial Doppler, echocardiography, and cognitive function tests.Women diagnosed with pre-eclampsia and normotensive controls are enrolled in the biobank at admission to Tygerberg University Hospital (Cape Town, South Africa). Biological samples and clinical data are collected at inclusion/delivery and during the hospital stay. Special investigations as per above are performed in a subset of women. After two months, women are followed up by telephonic interviews. This project aims to establish a biobank and database for severe organ complications of pre-eclampsia in a low-middle income country where the incidence of pre-eclampsia with organ complications is high. The study integrates different methods to investigate pre-eclampsia, focusing on improved understanding of pathophysiology, prediction of organ complications, and potentially future drug evaluation and discovery.
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