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Frontiers in Endocrinology 2024During pregnancy, there is a link between disruption of maternal immune tolerance and preeclampsia, but the molecular mechanisms that regulate maternal and fetal immune...
During pregnancy, there is a link between disruption of maternal immune tolerance and preeclampsia, but the molecular mechanisms that regulate maternal and fetal immune tolerance remain unclear. This study employs bioinformatics to identify new markers related to placental immune tolerance and explore their potential role in predicting preeclampsia. Analyzing preeclampsia-related gene expression profiles in the Gene Expression Omnibus (GEO) dataset reveals 211 differentially expressed genes (DEGs) in the placenta, mainly influencing immune cell differentiation and response pathways. Employing weighted gene co-expression network analysis (WGCNA) and lasso regression, four potential target genes (ANKRD37, CRH, LEP, SIGLEC6) are identified for potential prediction of preeclampsia. Validation using the GSE4707 dataset confirmed the diagnostic and predictive potential of these candidate genes. RT-qPCR verified up-regulation in the placenta, while ELISA showed their correlation with immune tolerance factors associated with placental immune tolerance. As a result of this study, identifies potential biomarkers associated with placental immunity and contributes to understanding the molecular mechanism of preeclampsia.
Topics: Humans; Pre-Eclampsia; Pregnancy; Female; Placenta; Immune Tolerance; Biomarkers; Gene Expression Profiling; Computational Biology; Transcriptome; Adult
PubMed: 38894741
DOI: 10.3389/fendo.2024.1385154 -
International Journal of Molecular... Jun 2024South Africa is the epicentre of the global HIV pandemic, with 13.9% of its population infected. Preeclampsia (PE), a hypertensive disorder of pregnancy, is often... (Review)
Review
South Africa is the epicentre of the global HIV pandemic, with 13.9% of its population infected. Preeclampsia (PE), a hypertensive disorder of pregnancy, is often comorbid with HIV infection, leading to multi-organ dysfunction and convulsions. The exact pathophysiology of preeclampsia is triggered by an altered maternal immune response or defective development of maternal tolerance to the semi-allogenic foetus via the complement system. The complement system plays a vital role in the innate immune system, generating inflammation, mediating the clearance of microbes and injured tissue materials, and a mediator of adaptive immunity. Moreover, the complement system has a dual effect, of protecting the host against HIV infection and enhancing HIV infectivity. An upregulation of regulatory proteins has been implicated as an adaptive phenomenon in response to elevated complement-mediated cell lysis in HIV infection, further aggravated by preeclamptic complement activation. In light of the high prevalence of HIV infection and preeclampsia in South Africa, this review discusses the association of complement proteins and their role in the synergy of HIV infection and preeclampsia in South Africa. It aims to identify women at elevated risk, leading to early diagnosis and better management with targeted drug therapy, thereby improving the understanding of immunological dysregulation.
Topics: Humans; Pre-Eclampsia; Pregnancy; HIV Infections; Female; Complement System Proteins; Pregnancy Complications, Infectious; South Africa; Comorbidity; Complement Activation
PubMed: 38892429
DOI: 10.3390/ijms25116232 -
International Journal of Molecular... Jun 2024The placenta plays a key role in several adverse obstetrical outcomes, such as preeclampsia, intrauterine growth restriction and gestational diabetes mellitus. The early... (Review)
Review
The placenta plays a key role in several adverse obstetrical outcomes, such as preeclampsia, intrauterine growth restriction and gestational diabetes mellitus. The early identification of at-risk pregnancies could significantly improve the management, therapy and prognosis of these pregnancies, especially if these at-risk pregnancies are identified in the first trimester. The aim of this review was to summarize the possible biomarkers that can be used to diagnose early placental dysfunction and, consequently, at-risk pregnancies. We divided the biomarkers into proteins and non-proteins. Among the protein biomarkers, some are already used in clinical practice, such as the sFLT1/PLGF ratio or PAPP-A; others are not yet validated, such as HTRA1, Gal-3 and CD93. In the literature, many studies analyzed the role of several protein biomarkers, but their results are contrasting. On the other hand, some non-protein biomarkers, such as miR-125b, miR-518b and miR-628-3p, seem to be linked to an increased risk of complicated pregnancy. Thus, a first trimester heterogeneous biomarkers panel containing protein and non-protein biomarkers may be more appropriate to identify and discriminate several complications that can affect pregnancies.
Topics: Humans; Pregnancy; Female; Biomarkers; Pregnancy Trimester, First; Placenta; Pregnancy Outcome; Pre-Eclampsia; MicroRNAs; Pregnancy-Associated Plasma Protein-A; Diabetes, Gestational
PubMed: 38892323
DOI: 10.3390/ijms25116136 -
BMJ Open Jun 2024Preterm pre-eclampsia is a leading cause of maternal morbidity and mortality. The Pre-eclampsia Intervention 2 (PI 2) trial suggested that metformin sustained release...
INTRODUCTION
Preterm pre-eclampsia is a leading cause of maternal morbidity and mortality. The Pre-eclampsia Intervention 2 (PI 2) trial suggested that metformin sustained release (XR) may prolong gestation by a week in pregnant women undergoing expectant management (7.6 days, geometric mean ratio 1.39, 95% CI 0.99 to 1.95; p=0.057). These findings should be confirmed with a larger sample size, and we need to know if such a prolongation improves neonatal outcome. Here, we describe the protocol for such a follow-up trial.
METHODS
The PI 3 trial is a phase III, intention-to-treat, double-blind, placebo-controlled randomised clinical trial to assess if metformin XR can prolong gestation and improve neonatal outcomes in women undergoing expectant management for preterm pre-eclampsia. We will recruit women who are between 26+0 and 31+6 weeks pregnant. Women will be randomised to receive either 3 g metformin XR or an identical placebo in divided daily doses. The primary outcome is prolongation of pregnancy. Secondary outcomes are neonatal birth weight and length of neonatal care admission (an indicator of neonatal health at birth). All other outcomes will be exploratory. We will record tolerability and adverse events. We plan a sample size of 500 participants to be powered for the primary and secondary outcomes.
ETHICS AND DISSEMINATION
PI 3 has ethical approval (Health Research Ethics Committee 2, Stellenbosch University, Protocol number M21/03/007, Project ID 21639, Federal Wide Assurance Number 00001372, Institutional Review Board Number IRB0005239), and is registered with the Pan African Clinical Trial Registry (PACTR202104532026017) and the South African Medicine Control Council (20211211). Data will be presented at international conferences and published in peer-reviewed journals.
TRIAL REGISTRATION NUMBER
PACTR202104532026017).
Topics: Humans; Pregnancy; Female; Metformin; Pre-Eclampsia; Double-Blind Method; South Africa; Hypoglycemic Agents; Infant, Newborn; Randomized Controlled Trials as Topic; Adult; Pregnancy Outcome
PubMed: 38890136
DOI: 10.1136/bmjopen-2023-082880 -
BMJ Case Reports Jun 2024Eclampsia spectrum disorders are a set of serious complications of pregnancy that commonly present after 20 weeks of gestation. There is an association between molar...
Eclampsia spectrum disorders are a set of serious complications of pregnancy that commonly present after 20 weeks of gestation. There is an association between molar pregnancy, a gestational trophoblastic disease resulting from abnormal fertilisation and gametogenesis, and eclampsia spectrum disorders which can result in manifestation of pre-eclamptic symptomatology earlier than 20 weeks of gestation. We report a case of a gravida 1 para 0 in her mid 20s at 16-weeks gestation presenting with partial hydatidiform mole who developed eclampsia, haemolysis, elevated liver enzymes and low platelets syndrome and posterior reversible encephalopathy syndrome. Ultrasound findings were consistent with molar pregnancy and pathology confirmed partial molar pregnancy with triploid 69, XYY karyotype. This case highlights the early onset potential of eclampsia spectrum disorders in molar pregnancies while suggesting screening such patients for hypertensive disorders.
Topics: Humans; Female; Hydatidiform Mole; Pregnancy; HELLP Syndrome; Eclampsia; Adult; Uterine Neoplasms; Posterior Leukoencephalopathy Syndrome
PubMed: 38890113
DOI: 10.1136/bcr-2023-258188 -
IMeta Apr 2024Numerous studies have demonstrated the pivotal roles of intestinal microbiota in many physiopathological processes through complex interactions with the host. As a... (Review)
Review
Numerous studies have demonstrated the pivotal roles of intestinal microbiota in many physiopathological processes through complex interactions with the host. As a unique period in a woman's lifespan, pregnancy is characterized by changes in hormones, immunity, and metabolism. The gut microbiota also changes during this period and plays a crucial role in maintaining a healthy pregnancy. Consequently, anomalies in the composition and function of the gut microbiota, namely, gut microbiota dysbiosis, can predispose individuals to various pregnancy complications, posing substantial risks to both maternal and neonatal health. However, there are still many controversies in this field, such as "sterile womb" versus "in utero colonization." Therefore, a thorough understanding of the roles and mechanisms of gut microbiota in pregnancy and its complications is essential to safeguard the health of both mother and child. This review provides a comprehensive overview of the changes in gut microbiota during pregnancy, its abnormalities in common pregnancy complications, and potential etiological implications. It also explores the potential of gut microbiota in diagnosing and treating pregnancy complications and examines the possibility of gut-derived bacteria residing in the uterus/placenta. Our aim is to expand knowledge in maternal and infant health from the gut microbiota perspective, aiding in developing new preventive and therapeutic strategies for pregnancy complications based on intestinal microecology.
PubMed: 38882493
DOI: 10.1002/imt2.167 -
Cureus Jun 2024Advances in assisted reproductive technologies have enabled postmenopausal women to achieve pregnancy beyond their reproductive lifespan. Although rare, these...
Advances in assisted reproductive technologies have enabled postmenopausal women to achieve pregnancy beyond their reproductive lifespan. Although rare, these pregnancies are challenging and require a multidisciplinary approach due to the higher prevalence of medical comorbidities in this population. The placenta accreta spectrum is characterized by an abnormal invasion of chorionic villi into the myometrium. Risk factors associated with the placenta accreta spectrum include prior uterine surgeries, advanced maternal age, multiparity, in vitro fertilization, and placenta previa. We present a case of a 59-year-old postmenopausal woman with chronic hypertension, stage II chronic kidney injury, and superimposed pre-eclampsia who underwent cesarean delivery complicated by suspected focal placenta accreta. Histopathological examination revealed significant deviations from normative placental architecture, emphasizing the invasion of the villi. Further, congested blood vessels and the presence of inflammatory cells, along with heightened collagen deposition, suggest an underlying pathological process affecting placental health. These findings underscore a perturbation of placental homeostasis, emphasizing the necessity for further investigation into the mechanisms contributing to placental pathology in postmenopausal pregnancies.
PubMed: 38882221
DOI: 10.7759/cureus.62332 -
PeerJ 2024COVID-19 is an infectious pathology that shows vascular changes during pregnancy, as well as in the placentas. The main objectives of this study were to estimate the...
BACKGROUND
COVID-19 is an infectious pathology that shows vascular changes during pregnancy, as well as in the placentas. The main objectives of this study were to estimate the prevalence and the risk factors for preeclampsia in hospitalized pregnant women with COVID-19. As well as comparing maternal and perinatal outcomes in hospitalized pregnant women with COVID-19 and preeclampsia with those without preeclampsia.
METHODS
Prospective cohort study of 100 hospitalized pregnant women from two tertiary hospitals, diagnosed with COVID-19, and divided into two groups: PE+ group (pregnant women with COVID-19 and preeclampsia) and PE- group (pregnant women with COVID-19 without preeclampsia). These pregnant women had prevalence, risk factors, maternal and perinatal data analyzed.
RESULTS
The prevalence of preeclampsia was 11%. Severe COVID-19 was the main risk factor for preeclampsia (OR = 8.18 [CI 1.53-43.52]), as well as fetal growth restriction was the main perinatal outcome (OR = 8.90 [CI 1.52-38.4]). Comorbidities were more frequent in the PE+ group (63.6% 31.5%, = 0.03), as well as prematurity (81.8% 41.6%, = 0.02), low birth weight (63.6% 24.7%, = 0.01), and the need for neonatal intensive care admission of the newborn (63.6% 27.0%, = 0.03). Pregnant women with PE had twice as long a length of stay in the intensive care unit (RR = 2.35 [CI 1.34-4.14]). Although maternal mortality was more frequent among pregnant women with PE, it was not statistically significant.
CONCLUSIONS
Prevalence of preeclampsia in hospitalized pregnant women with COVID-19 was 11%. Severe COVID-19 was the main risk factor for preeclampsia and associated comorbidities increased the risk for developing preeclampsia. Long length of stay in the intensive care unit was the main maternal outcome and fetal growth restriction was the main perinatal outcome of preeclampsia.
Topics: Humans; Pregnancy; Female; Pre-Eclampsia; COVID-19; Brazil; Prospective Studies; Adult; Tertiary Care Centers; Pregnancy Complications, Infectious; Risk Factors; Pregnancy Outcome; Prevalence; SARS-CoV-2; Infant, Newborn; Fetal Growth Retardation; Comorbidity
PubMed: 38881857
DOI: 10.7717/peerj.17481 -
Metabolomics : Official Journal of the... Jun 2024Preeclampsia is a pregnancy-specific clinical syndrome and can be subdivided into early-onset preeclampsia (EOPE) and late-onset preeclampsia (LOPE) according to the...
BACKGROUND
Preeclampsia is a pregnancy-specific clinical syndrome and can be subdivided into early-onset preeclampsia (EOPE) and late-onset preeclampsia (LOPE) according to the gestational age of delivery. Patients with preeclampsia have aberrant lipid metabolism. This study aims to compare serum lipid profiles of normal pregnant women with EOPE or LOPE and screening potential biomarkers to diagnose EOPE or LOPE.
METHODS
Twenty normal pregnant controls (NC), 19 EOPE, and 19 LOPE were recruited in this study. Untargeted lipidomics based on ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to compare their serum lipid profiles.
RESULTS
The lipid metabolism profiles significantly differ among the NC, EOPE, and LOPE. Compared to the NC, there were 256 and 275 distinct lipids in the EOPE and LOPE, respectively. Furthermore, there were 42 different lipids between the LOPE and EOPE, of which eight were significantly associated with fetal birth weight and maternal urine protein. The five lipids that both differed in the EOPE and LOPE were DGTS (16:3/16:3), LPC (20:3), LPC (22:6), LPE (22:6), PC (18:5e/4:0), and a combination of them were a potential biomarker for predicting EOPE or LOPE. The receiver operating characteristic analysis revealed that the diagnostic power of the combination for distinguishing the EOPE from the NC and for distinguishing the LOPE from the NC can reach 1.000 and 0.992, respectively. The association between the lipid modules and clinical characteristics of EOPE and LOPE was investigated by the weighted gene co-expression network analysis (WGCNA). The results demonstrated that the main different metabolism pathway between the EOPE and LOPE was enriched in glycerophospholipid metabolism.
CONCLUSIONS
Lipid metabolism disorders may be a potential mechanism of the pathogenesis of preeclampsia. Lipid metabolites have the potential to serve as biomarkers in patients with EOPE or LOPE. Furthermore, lipid metabolites correlate with clinical severity indicators for patients with EOPE and LOPE, including fetal birth weight and maternal urine protein levels.
Topics: Humans; Pregnancy; Female; Pre-Eclampsia; Lipidomics; Adult; Biomarkers; Lipids; Tandem Mass Spectrometry; Lipid Metabolism; Chromatography, High Pressure Liquid; Gestational Age
PubMed: 38879866
DOI: 10.1007/s11306-024-02134-x -
The Lancet. Global Health Jul 2024We developed a comprehensive database of medicines that are used or are being investigated for pre-eclampsia or eclampsia, preterm birth or labour, postpartum... (Review)
Review
We developed a comprehensive database of medicines that are used or are being investigated for pre-eclampsia or eclampsia, preterm birth or labour, postpartum haemorrhage, intrauterine growth restriction, and fetal distress and that were in active development between 2000 and 2021. A total of 444 candidates were identified: approximately half of candidates were in active development, two-thirds had been repurposed after initially being used for another condition, and just under half were in preclinical studies. Only 64 candidates were in active late-stage (phase 3) development as of Oct 25, 2021, and given the slow pace of biomedical development, it could take years before any of these products eventually make it to market. A lack of innovation for maternal health medicines persists, and the market continues to fail pregnant individuals. There is a need for collective action from all relevant stakeholders to accelerate investment in the development of new or improved medicines for pregnancy-related conditions.
Topics: Humans; Female; Pregnancy; Maternal Health; Pregnancy Complications; Drug Development; Pre-Eclampsia
PubMed: 38876763
DOI: 10.1016/S2214-109X(24)00144-X