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1.
BMC Pregnancy Childbirth ; 24(1): 414, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38849756

ABSTRACT

CircRNAs are a class of endogenous non-coding RNAs implicated in the pathogenesis of many pregnancy related diseases, one of which is pre-eclampsia (PE). This study aims to investigate the role of CircPAPPA2 (circbase ID: hsa_circ_0015382) in regulating the migration and invasion of trophoblast cells. RNA sequencing was used to identify the differentially expressed circRNAs in placenta of PE and normal pregnant women. Quantitative polymerase chain reaction (qRT-PCR) was used to verify the expression of circPAPPA2 and two miRNAs (miR-942-5p, 5006-3p) in placenta of PE and normal pregnant women. CCK8 and transwell experiments were performed to assess the function of circPAPPA2 in PE development.The interaction between circPAPPA2 and miR-942-5p/miR-5006-3p was verified by dual-luciferase reporter assay. Finally, bioinformatics analyzed with gene ontology, Kyoto Encyclopedia of the target genes. The results showed that the expression of circPAPPA2 was increased in placenta of PE pregnant women. Also, circPAPPA2 impedes trophoblasts cell proliferation and invasion. Moreover, the expression of circPAPPA2 was positively correlated with systolic blood pressure and urine protein. In addition, circPAPPA2 serves as a sponge of miR-942-5p and miR-5006-3p. In conclusion, CircPAPPA2 regulates trophoblasts cell proliferation and invasion by mediating the miR-942/miR-5006-3p.


Subject(s)
MicroRNAs , Placenta , Pre-Eclampsia , RNA, Circular , Trophoblasts , Humans , Pre-Eclampsia/genetics , Pre-Eclampsia/metabolism , Female , MicroRNAs/genetics , MicroRNAs/metabolism , Pregnancy , RNA, Circular/genetics , Trophoblasts/metabolism , Placenta/metabolism , Adult , Cell Movement/genetics , Cell Proliferation/genetics , Case-Control Studies
2.
Niger J Clin Pract ; 27(5): 599-603, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38842709

ABSTRACT

BACKGROUND AND AIM: Preeclampsia, a pregnancy complication associated with significant maternal and perinatal mortality and morbidity, has been found to be closely linked to dysfunction in the blood coagulation-fibrinolysis system. However, the relationship between hematologic data and severity and onset time of preeclampsia remains unclear. This study aimed to identify specific hematologic parameters in both preeclamptic and normotensive pregnant women and determine their potential significance in the pathogenesis of preeclampsia. MATERIALS AND METHODS: A total of 112 patients with gestational hypertension disease were divided into two groups: early-onset preeclampsia (32 cases) and late-onset preeclampsia (80 cases). A control group of 82 normotensive pregnant women matched for age and parity was also selected. Blood samples were collected from all participants to test for specific hematologic parameters. RESULTS: Mild and severe preeclampsia were associated with lower hemoglobin level (P = 0.01 and P = 0.03, respectively), higher mean platelet volume (P = 0.01 and P = 0.01, respectively) and fibrinogen (P = 0.01 and P = 0.01, respectively), and shorter prothrombin time (P = 0.02 and P = 0.01, respectively) and activated partial thromboplastin time (P = 0.01 and P = 0.02, respectively). CONCLUSION: These findings have provided evidence on the hematologic coagulative actors in the pathogenesis and severity of preeclampsia.


Subject(s)
Pre-Eclampsia , Humans , Female , Pregnancy , Adult , Pre-Eclampsia/blood , Pre-Eclampsia/physiopathology , Pre-Eclampsia/diagnosis , Case-Control Studies , Hypertension, Pregnancy-Induced/blood , Hypertension, Pregnancy-Induced/physiopathology , Blood Coagulation/physiology , Severity of Illness Index , Young Adult , Fibrinogen/metabolism , Fibrinogen/analysis , Prothrombin Time , Mean Platelet Volume , Hemoglobins/analysis , Partial Thromboplastin Time
3.
Front Endocrinol (Lausanne) ; 15: 1386309, 2024.
Article in English | MEDLINE | ID: mdl-38846494

ABSTRACT

Introduction: Leptin and its receptors are expressed by the human placenta throughout gestation, yet the role of leptin in early human placental development is not well characterized. Leptin is overexpressed in the placentas from preeclamptic (PE) pregnancies. PE can result from the impaired invasion of fetal placental cells, cytotrophoblasts (CTBs), into the maternal decidua. We hypothesized that elevated leptin levels would impair human CTB invasion. Methods: The effects of leptin on the invasion of human CTBs were evaluated in three cell models, HTR-8/SVneo cells, primary CTBs, and placental villous explants using invasion assays. Further, leptin receptor expression was characterized in all three cell models using RT-PCR. Further phosphokinase assays were performed in HTR-8/SVneo cells to determine signaling pathways involved in CTB invasion in response to differential leptin doses. Results: We found that, prior to 8 weeks gestation, leptin promoted CTB invasion in the explant model. After 11 weeks gestation in explants, primary CTBs and in HTR-8/SVneo cells, leptin promoted invasion at moderate but not at high concentrations. Further, leptin receptor characterization revealed that leptin receptor expression did not vary over gestation, however, STAT, PI3K and MAPK pathways showed different signaling in response to varied leptin doses. Discussion: These data suggest that the excess placental leptin observed in PE may cause impaired CTB invasion as a second-trimester defect. Leptin's differential effect on trophoblast invasion may explain the role of hyperleptinemia in preeclampsia pathogenesis.


Subject(s)
Gestational Age , Leptin , Receptors, Leptin , Trophoblasts , Humans , Trophoblasts/metabolism , Trophoblasts/drug effects , Trophoblasts/pathology , Leptin/metabolism , Leptin/pharmacology , Female , Pregnancy , Receptors, Leptin/metabolism , Receptors, Leptin/genetics , Placenta/metabolism , Placenta/drug effects , Placenta/pathology , Pre-Eclampsia/metabolism , Pre-Eclampsia/pathology , Dose-Response Relationship, Drug , Signal Transduction , Placentation/drug effects , Cell Movement/drug effects
4.
Sci Rep ; 14(1): 12672, 2024 06 03.
Article in English | MEDLINE | ID: mdl-38830948

ABSTRACT

Pre-eclampsia (PE) is a hypertensive disorder characterised by systemic vascular resistance and endothelial dysfunction. It is known to influence choroidal thickness (CT). No previous studies have explored the antepartum and postpartum changes in CT with respect to the protein-creatinine ratio (PCR), a measure of proteinuria that is a clinical hallmark of PE. This study evaluated the correlations between antepartum and postpartum CT and the PCR in patients with PE. In this retrospective study, sixty-six eyes (66 patients) were analysed. The patients were divided into two groups according to the median PCR value (2.36 mg/mg): low PCR group (< 2.36 mg/mg) and high PCR group (≥ 2.36 mg/mg). Ophthalmologic clinical data were collected and assessed. We observed higher antepartum CT and higher mean arterial pressure in high PCR group than in low PCR group. Moreover, postpartum CT decreased significantly in high PCR group. In the multivariate analysis, CT changes were correlated with antepartum CT and antepartum PCR after logarithm transformation. In conclusion, a greater decrease in CT was observed in high PCR group than in low PCR group. Further, the antepartum PCR showed a correlation with the extent of CT reduction.


Subject(s)
Choroid , Postpartum Period , Pre-Eclampsia , Proteinuria , Humans , Female , Pre-Eclampsia/pathology , Pre-Eclampsia/physiopathology , Pregnancy , Adult , Choroid/pathology , Choroid/diagnostic imaging , Retrospective Studies , Creatinine/blood , Creatinine/urine
5.
PLoS One ; 19(6): e0304604, 2024.
Article in English | MEDLINE | ID: mdl-38833446

ABSTRACT

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is a serious liver conditions that negatively impacts obstetric and neonatal outcomes. Elevated levels of bile acid, particularly glycine conjugate, may compromise blood flow and cause functional hypoxia-ischemia. AIMS: This meta-analysis aims to assess the association between ICP and key pregnancy outcomes including emergency caesarian sections (C-sections), preeclampsia, hemorrhage, preterm birth, small for gestational age, admission rate to neonatal intensive care union (NICU), gestational age, and stillbirth. MATERIALS AND METHODS: Literature search across five databases (PubMed, Embase, Web of Science) was done to detect relevant studies published up until June 2023. Meta-analysis of the identified studies was done using a random-effects model, and the results presented as Odds ratio (OR). RESULTS: A literature search identified 662 studies. Of them, 21 met the inclusion criteria. There was a significant association between ICP and odds of C-section (OR: 1.42, p <0.001), preeclampsia (OR: 2.64, p <0.001), NICU admission (OR: 2.1, p <0.001), and pre-term birth (OR: 2.64, p <0.001). ICP was not associated with postpartum hemmorhage (OR: 1.31, p = 0.13), small for gestational age (OR: 0.87, p = 0.07), stillbirth (OR: 1.49, p = 0.29). CONCLUSIONS: Our results confirm the adverse effects of ICP on co-existing pregnancy complications, obstetric and neonatal outcomes. ICP in associated with severe complications including increased rates of preeclampsia, emergency C-sections, preterm births, l gestational periods and higher rates of NICU admissions. These results may assist healthcare professionals in formulating comprehensive care guidelines for expectant mothers and newborns.


Subject(s)
Cholestasis, Intrahepatic , Pregnancy Complications , Pregnancy Outcome , Premature Birth , Humans , Pregnancy , Cholestasis, Intrahepatic/complications , Cholestasis, Intrahepatic/epidemiology , Female , Pregnancy Complications/epidemiology , Infant, Newborn , Premature Birth/epidemiology , Stillbirth/epidemiology , Pre-Eclampsia/epidemiology , Cesarean Section , Gestational Age , Infant, Small for Gestational Age
6.
Rev Med Liege ; 79(5-6): 448-454, 2024 Jun.
Article in French | MEDLINE | ID: mdl-38869138

ABSTRACT

Preeclampsia is a pregnancy-specific condition characterized by gestational hypertension associated with proteinuria or organ dysfunction after 20 weeks of gestation. It complicates 2 to 8 % of pregnancies worldwide and represents the leading cause of maternal and fetal mortality in developed countries. The only definitive treatment remains termination of pregnancy and delivery of the placenta. Prompt assessment of maternal and fetal status should be held in search of severity criteria and adequate management of this condition according to gestational age. Foremost concerns for pregnant patients are impending eclampsia or placental abruption, while fetal complications arise from placental insufficiency and risks associated with premature pregnancy termination. The sole efficient prophylaxis of preeclampsia in current state of evidence is aspirin at a dosage of 160 mg per day in high risk patients. Preeclampsia is now recognized as a high-risk factor for cardiovascular, renal, and neurological diseases and should therefore be considered as an opportunity for screening and prevention.


La prééclampsie (PE) est un syndrome unique à la grossesse défini par une hypertension artérielle gravidique, associée à une protéinurie ou une atteinte d'organe après 20 semaines d'aménorrhée. Elle complique 2 à 8 % des grossesses à l'échelle mondiale, et représente la première cause de mortalité maternelle et fœtale dans les pays industrialisés. Le seul traitement curatif demeure l'arrêt de la grossesse et la délivrance du placenta. Cette pathologie justifie une évaluation rapide de l'état maternel et fœtal, afin de juger des critères de sévérité et d'orienter la prise en charge selon le terme de la grossesse. La menace maternelle est dominée par le risque de survenue d'une éclampsie ou d'un hématome rétroplacentaire alors que les complications fœtales découlent de l'insuffisance placentaire et des risques inhérents à un arrêt prématuré de grossesse. Le seul traitement préventif actuellement validé en prévention secondaire chez les patientes à haut risque est l'aspirine à une dose de 160 mg par jour. La PE est désormais reconnue comme un facteur de risque cardiovasculaire, rénal et neurologique, et doit être considérée, de ce fait, comme une opportunité de dépistage et de prévention.


Subject(s)
Pre-Eclampsia , Humans , Pregnancy , Pre-Eclampsia/prevention & control , Pre-Eclampsia/diagnosis , Female , Risk Factors
7.
Metabolomics ; 20(4): 65, 2024 Jun 16.
Article in English | MEDLINE | ID: mdl-38879866

ABSTRACT

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.


Subject(s)
Biomarkers , Lipidomics , Lipids , Pre-Eclampsia , Humans , Pregnancy , Female , Pre-Eclampsia/diagnosis , Pre-Eclampsia/blood , Pre-Eclampsia/metabolism , Lipidomics/methods , Adult , Biomarkers/blood , Lipids/blood , Lipids/analysis , Tandem Mass Spectrometry , Lipid Metabolism , Chromatography, High Pressure Liquid , Gestational Age
8.
Front Endocrinol (Lausanne) ; 15: 1385154, 2024.
Article in English | MEDLINE | ID: mdl-38894741

ABSTRACT

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.


Subject(s)
Biomarkers , Immune Tolerance , Placenta , Pre-Eclampsia , Humans , Pre-Eclampsia/immunology , Pre-Eclampsia/genetics , Pregnancy , Female , Placenta/metabolism , Placenta/immunology , Biomarkers/metabolism , Gene Expression Profiling , Computational Biology/methods , Transcriptome , Adult
9.
Front Endocrinol (Lausanne) ; 15: 1280692, 2024.
Article in English | MEDLINE | ID: mdl-38894748

ABSTRACT

Background: The prevalence of obesity among women of reproductive age is increasing worldwide, with implications for serious pregnancy complications. Methods: Following PRISMA guidelines, a systematic search was conducted in both Chinese and English databases up to December 30, 2020. Pregnancy complications and outcomes including gestational diabetes mellitus (GDM), gestational hypertension (GHTN), pre-eclampsia, cesarean section (CS), induction of labor (IOL), and postpartum hemorrhage (PPH) were analyzed. Random-effects or fixed-effects models were utilized to calculate the odds ratio (OR) with 95% confidence intervals (CIs). Results: Women with overweight and obesity issues exhibited significantly higher risks of GDM (OR, 2.92, 95%CI, 2.18-2.40 and 3.46, 95%CI, 3.05-3.94, respectively) and GHTN (OR, 2.08, 95%CI, 1.72-2.53 and 3.36, 95%CI, 2.81-4.00, respectively) compared to women of normal weight. Pre-eclampsia was also significantly higher in women with overweight or obesity, with ORs of 1.70 (95%CI, 1.44-2.01) and 2.82 (95%CI, 2.66-3.00), respectively. Additionally, mothers with overweight or obesity issues had significantly higher risks of CS (OR, 1.44, 95%CI, 1.41-1.47, and 2.23, 95%CI, 2.08-2.40), IOL (OR, 1.33, 95%CI, 1.30-1.35 and 1.96, 95%CI, 1.85-2.07), and PPH (OR, 1.67, 95%CI, 1.42-1.96 and 1.88, 95%CI, 1.55-2.29). Conclusion: Women with overweight or obesity issues face increased risks of pregnancy complications and adverse outcomes, indicating dose-dependent effects.


Subject(s)
Body Mass Index , Pregnancy Complications , Pregnancy Outcome , Humans , Pregnancy , Female , Pregnancy Complications/epidemiology , Pregnancy Outcome/epidemiology , Obesity/complications , Obesity/epidemiology , Diabetes, Gestational/epidemiology , Pre-Eclampsia/epidemiology , Cesarean Section/statistics & numerical data , Overweight/complications , Overweight/epidemiology , Postpartum Hemorrhage/epidemiology , Postpartum Hemorrhage/etiology
11.
BMJ Open ; 14(6): e082880, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38890136

ABSTRACT

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).


Subject(s)
Metformin , Pre-Eclampsia , Humans , Pregnancy , Female , Metformin/therapeutic use , Pre-Eclampsia/prevention & control , Double-Blind Method , South Africa , Hypoglycemic Agents/therapeutic use , Infant, Newborn , Randomized Controlled Trials as Topic , Adult , Pregnancy Outcome
12.
Front Immunol ; 15: 1389843, 2024.
Article in English | MEDLINE | ID: mdl-38873604

ABSTRACT

Objectives: Preeclampsia/eclampsia (PE), a critical complication during pregnancy, has been suggested to correlate with immune cell phenotypes and levels of circulating inflammatory proteins. Our study aimed to employ a two-sample mendelian randomization (MR) analysis to assess the potential causal effects of immune cell phenotypes and circulating inflammatory proteins on the onset of PE. Methods: We utilized summary-level data from genome-wide association studies (GWAS). This included statistics for 371 immune cell phenotypes from 3,757 individuals in the Sardinian founder population, and data on 91 circulating inflammatory proteins from 14,824 European ancestry participants. Additionally, genetic associations related to PE were extracted from the FinnGen consortium, involving 1,413 cases and 287,137 controls. We applied inverse variance weighting (IVW) and supplementary methods like MR-Egger, weighted median, and weighted mode to comprehensively assess potential causal links. Results: Our analysis revealed significant causal associations of several immune cells type and inflammatory proteins with PE. Out of the immune cell phenotypes analyzed, six immune phenotypes emerged as significant risk factors (p <0.01), mainly include CD4 on activated and secreting CD4 regulatory T cells, CD28 on CD39+ CD4+ T cells, CD127- CD8+ T cell absolute cell (AC) counts, HLA DR on HLA DR+ CD8+ T cell, CD66b on CD66b++ myeloid cells, and HLA DR on dendritic cells. And ten were identified as protective factors (p <0.01). Such as CD45 on CD33br HLA DR+ CD14-, CD33+ HLA DR+ AC, CD33+ HLA DR+ CD14- AC, CD33+ HLA DR+ CD14dim AC, CD27 on CD24+ CD27+ B cell, CD20- CD38- %B cell, IgD- CD24- %B cell CD80 on plasmacytoid DC, CD25 on CD4+ T cell, and CD25 on activated & secreting CD4 regulatory T cell. Furthermore, among the inflammatory proteins studied, five showed a significant association with PE, with three offering protective effects mainly include that C-X-C motif chemokine 1, tumor necrosis factor ligand superfamily member 14, and C-C motif chemokine 19 and two exacerbating PE risk such as STAM-binding domain and Interleukin-6 (p <0.05). Conclusions: Our study highlights the pivotal roles played by diverse immune cell phenotypes and circulating inflammatory proteins in the pathophysiology of PE. These findings illuminate the underlying genetic mechanisms, emphasizing the criticality of immune regulation during pregnancy. Such insights could pave the way for novel intervention strategies in managing PE, potentially enhancing maternal and neonatal health outcomes.


Subject(s)
Genome-Wide Association Study , Pre-Eclampsia , Humans , Female , Pre-Eclampsia/immunology , Pre-Eclampsia/genetics , Pre-Eclampsia/blood , Pregnancy , Genetic Predisposition to Disease , Mendelian Randomization Analysis , Phenotype , Polymorphism, Single Nucleotide , Biomarkers , Adult , Inflammation/immunology , Inflammation/genetics
13.
PeerJ ; 12: e17481, 2024.
Article in English | MEDLINE | ID: mdl-38881857

ABSTRACT

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% vs 31.5%, p = 0.03), as well as prematurity (81.8% vs 41.6%, p = 0.02), low birth weight (63.6% vs 24.7%, p = 0.01), and the need for neonatal intensive care admission of the newborn (63.6% vs 27.0%, p = 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.


Subject(s)
COVID-19 , Pre-Eclampsia , Pregnancy Complications, Infectious , Pregnancy Outcome , SARS-CoV-2 , Tertiary Care Centers , Humans , Pregnancy , Female , Pre-Eclampsia/epidemiology , COVID-19/epidemiology , COVID-19/mortality , Brazil/epidemiology , Prospective Studies , Adult , Pregnancy Complications, Infectious/epidemiology , Pregnancy Complications, Infectious/virology , Risk Factors , Pregnancy Outcome/epidemiology , Prevalence , Infant, Newborn , Fetal Growth Retardation/epidemiology , Fetal Growth Retardation/virology , Comorbidity
14.
JAMA Netw Open ; 7(6): e2416844, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38869897

ABSTRACT

Importance: Innovative approaches are needed to address the increasing rate of postpartum morbidity and mortality associated with hypertensive disorders. Objective: To determine whether assessing maternal blood pressure (BP) and associated symptoms at time of well-child visits is associated with increased detection of postpartum preeclampsia and need for hospitalization for medical management. Design, Setting, and Participants: This is a pre-post quality improvement (QI) study. Individuals who attended the well-child visits between preimplementation (December 2017 to December 2018) were compared with individuals who enrolled after the implementation of the QI program (March 2019 to December 2019). Individuals were enrolled at an academic pediatric clinic. Eligible participants included birth mothers who delivered at the hospital and brought their newborn for well-child check at 2 days, 2 weeks, and 2 months. A total of 620 individuals were screened in the preintervention cohort and 680 individuals were screened in the QI program. Data was analyzed from March to July 2022. Exposures: BP evaluation and preeclampsia symptoms screening were performed at the time of the well-child visit. A management algorithm-with criteria for routine or early postpartum visits, or prompt referral to the obstetric emergency department-was followed. Main Outcome and Measures: Readmission due to postpartum preeclampsia. Comparisons across groups were performed using a Fisher exact test for categorical variables, and t tests or Mann-Whitney tests for continuous variables. Results: A total of 595 individuals (mean [SD] age, 27.2 [6.1] years) were eligible for analysis in the preintervention cohort and 565 individuals (mean [SD] age, 27.0 [5.8] years) were eligible in the postintervention cohort. Baseline demographic information including age, race and ethnicity, body mass index, nulliparity, and factors associated with increased risk for preeclampsia were not significantly different in the preintervention cohort and postintervention QI program. The rate of readmission for postpartum preeclampsia differed significantly in the preintervention cohort (13 individuals [2.1%]) and the postintervention cohort (29 individuals [5.6%]) (P = .007). In the postintervention QI cohort, there was a significantly earlier time frame of readmission (median [IQR] 10.0 [10.0-11.0] days post partum for preintervention vs 7.0 [6.0-10.5] days post partum for postintervention; P = .001). In both time periods, a total of 42 patients were readmitted due to postpartum preeclampsia, of which 21 (50%) had de novo postpartum preeclampsia. Conclusions and Relevance: This QI program allowed for increased and earlier readmission due to postpartum preeclampsia. Further studies confirming generalizability and mitigating associated adverse outcomes are needed.


Subject(s)
Pre-Eclampsia , Humans , Female , Adult , Pregnancy , Pre-Eclampsia/diagnosis , Pre-Eclampsia/therapy , Early Diagnosis , Quality Improvement , Patient Readmission/statistics & numerical data , Postpartum Period , Hypertension/diagnosis , Hypertension/therapy , Infant, Newborn , Puerperal Disorders/therapy , Puerperal Disorders/diagnosis
15.
FASEB J ; 38(13): e23706, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38877842

ABSTRACT

The etiology of preeclampsia (PE), a complex and multifactorial condition, remains incompletely understood. DNA methylation, which is primarily regulated by three DNA methyltransferases (DNMTs), DNMT1, DNMT3A, and DNMT3B, plays a vital role in early embryonic development and trophectoderm differentiation. Yet, how DNMTs modulate trophoblast fusion and PE development remains unclear. In this study, we found that the DNMTs expression was downregulated during trophoblast cells fusion. Downregulation of DNMTs was observed during the reconstruction of the denuded syncytiotrophoblast (STB) layer of placental explants. Additionally, overexpression of DNMTs inhibited trophoblast fusion. Conversely, treatment with the DNA methylation inhibitor 5-aza-CdR decreased the expression of DNMTs and promoted trophoblast fusion. A combined analysis of DNA methylation data and gene transcriptome data obtained from the primary cytotrophoblasts (CTBs) fusion process identified 104 potential methylation-regulated differentially expressed genes (MeDEGs) with upregulated expression due to DNA demethylation, including CD59, TNFAIP3, SDC1, and CDK6. The transcription regulation region (TRR) of TNFAIP3 showed a hypomethylation with induction of 5-aza-CdR, which facilitated CREB recruitment and thereby participated in regulating trophoblast fusion. More importantly, clinical correlation analysis of PE showed that the abnormal increase in DNMTs may be involved in the development of PE. This study identified placental DNA methylation-regulated genes that may contribute to PE, offering a novel perspective on the role of epigenetics in trophoblast fusion and its implication in PE development.


Subject(s)
DNA (Cytosine-5-)-Methyltransferases , DNA Methylation , Pre-Eclampsia , Trophoblasts , Trophoblasts/metabolism , Female , Pre-Eclampsia/genetics , Pre-Eclampsia/metabolism , Pre-Eclampsia/pathology , Pregnancy , Humans , DNA (Cytosine-5-)-Methyltransferases/genetics , DNA (Cytosine-5-)-Methyltransferases/metabolism , Cell Fusion , Placenta/metabolism , DNA (Cytosine-5-)-Methyltransferase 1/metabolism , DNA (Cytosine-5-)-Methyltransferase 1/genetics
16.
BMC Pregnancy Childbirth ; 24(1): 424, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38872116

ABSTRACT

OBJECTIVE: To establish the population pharmacokinetics (PPK) of magnesium sulfate (MgSO4)in women with preeclampsia (PE), and to determine the key covariates having an effect in magnesium pharmacokinetics in Chinese PE. METHODS: Pregnant women with PE prescribed MgSO4 were enrolled in this prospective study from April 2021 to April 2023. On the initial day of administration, the patients were administered a loading dose of 5 g in conjunction with 10 g of magnesium sulfate as a maintenance dose. On the second day, only the maintenance dose was administration, and maternal blood samples were taken at 0, 4, 5, and 12 h after the second day's 10 g maintenance dose. The software Phoenix was used to estimate PPK parameters of MgSO4, such as clearance (CL) and volume of distribution (V), and to model PPK models with patient demographic, clinical, and laboratory covariates. RESULTS: A total of 199 blood samples were collected from 51 women with PE and PPK profiles were analyzed. The PPK of MgSO4 is consistent with to a one-compartment model. The base model adequately described the maternal serum magnesium concentrations after magnesium administration. The population parameter estimates were as follows: CL was 2.98 L/h, V was 25.07 L. The model predictions changed significantly with covariates (BMI, creatinine clearance, and furosemide). Furosemide statistically influences V. The creatinine clearance, BMI and furosemide jointly affects CL. Monte Carlo simulation results showed that a loading dose combined with a maintenance dose would need to be administered daily to achieve the therapeutic blood magnesium concentrations. For the non-furosemide group, the optimal dosing regimen was a 5 g loading dose combined with a 10 g maintenance dose of MgSO4. For the furosemide group, the optimal dosing regimen was a 2.5 g loading dose combined with a 10 g maintenance dose of MgSO4. CONCLUSIONS: The magnesium PPK model was successfully developed and evaluated in Chinese preeclampsia population, and the dose optimization of MgSO4 was completed through Monte Carlo simulation.


Subject(s)
Magnesium Sulfate , Pre-Eclampsia , Humans , Female , Magnesium Sulfate/administration & dosage , Magnesium Sulfate/pharmacokinetics , Pre-Eclampsia/drug therapy , Pre-Eclampsia/blood , Pregnancy , Adult , Prospective Studies , China , Young Adult , Dose-Response Relationship, Drug , East Asian People
17.
Am J Pathol ; 194(7): 1162-1170, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38880601

ABSTRACT

The placenta plays a crucial role in pregnancy success. ΔNp63α (p63), a transcription factor from the TP53 family, is highly expressed in villous cytotrophoblasts (CTBs), the epithelial stem cells of the human placenta, and is involved in CTB maintenance and differentiation. We examined the mechanisms of action of p63 by identifying its downstream targets. Gene expression changes were evaluated following overexpression and knockdown of p63 in the JEG3 choriocarcinoma cell line, using microarray-based RNA profiling. High-temperature requirement A4 (HTRA4), a placenta-specific serine protease involved in trophoblast differentiation and altered in preeclampsia, was identified as a gene reciprocally regulated by p63, and its expression was characterized in primary human placental tissues by RNA-sequencing and in situ hybridization. Potential p63 DNA-binding motifs were identified in the HTRA4 promoter, and p63 occupancy at some of these sites was confirmed using chromatin immunoprecipitation, followed by quantitative PCR in both JEG3 and trophoblast stem cells. These data begin to identify members of the transcriptional network downstream of p63, thus laying the groundwork for probing mechanisms by which this important transcription factor regulates trophoblast stemness and differentiation.


Subject(s)
Transcription Factors , Trophoblasts , Humans , Trophoblasts/metabolism , Female , Pregnancy , Transcription Factors/metabolism , Transcription Factors/genetics , Serine Endopeptidases/metabolism , Serine Endopeptidases/genetics , Cell Differentiation/genetics , Cell Line, Tumor , Tumor Suppressor Proteins/metabolism , Tumor Suppressor Proteins/genetics , Placenta/metabolism , Serine Proteases/metabolism , Serine Proteases/genetics , Promoter Regions, Genetic/genetics , Pre-Eclampsia/genetics , Pre-Eclampsia/metabolism , Pre-Eclampsia/pathology , Transcription, Genetic
18.
PLoS One ; 19(6): e0304314, 2024.
Article in English | MEDLINE | ID: mdl-38861573

ABSTRACT

BACKGROUND: Preeclampsia is one of the three leading causes of worldwide maternal mortality. Oxidative stress-mediated endothelial damage is expected to be an ultimate common mechanism in the pathophysiology of preeclampsia. The role of bioamines is also well-established in the induction of preeclampsia. This project is aimed to understand the factors which may affect the induction, progression, and aggravation of preeclampsia and oxidative stress during pregnancy. This study will explore the methylation pattern of the Catechol-O-methyltransferase gene to determine its role in the pathogenesis of preeclampsia, association of Val158Met polymorphism with a wide range of oxidative stress biomarkers, major antioxidants vitamins, and blood pressure regulating amines in preeclamptic Pakistani women. METHODS AND ANALYSIS: In this prospective case-control study, 85 preeclamptic and 85 normotensive pregnant women will be recruited in their third trimesters. DNA will be extracted from peripheral blood and Val158Met polymorphism in the Catechol-O-methyltransferase gene will be examined on PCR amplified product digested with Hin1II (NlaIII) restriction enzyme, further validated by Sanger sequencing. Methylation-sensitive PCR will also be performed. Oxidative stress biomarkers, antioxidant vitamins, bioamines, and catechol-O-methyltransferase levels will be measured by ELISA. The data will be used to correlate maternal and fetal outcomes in both groups. DISCUSSION: This study will help to identify and understand the multifactorial path and cause-effect relationship of gene polymorphism, oxidative stress biomarkers, major antioxidants vitamins, and blood pressure regulating amines in the pathogenesis and aggravation of preeclampsia in the Pakistani population. The outcome of this project will be particularly helpful in reducing the incidence of preeclampsia and further improving its management.


Subject(s)
Biomarkers , Catechol O-Methyltransferase , Oxidative Stress , Pre-Eclampsia , Adult , Female , Humans , Pregnancy , Antioxidants/metabolism , Biomarkers/blood , Case-Control Studies , Catechol O-Methyltransferase/genetics , Genetic Predisposition to Disease , Oxidative Stress/genetics , Pakistan , Polymorphism, Genetic , Polymorphism, Single Nucleotide , Pre-Eclampsia/genetics , Prospective Studies , Young Adult
19.
PLoS One ; 19(6): e0286361, 2024.
Article in English | MEDLINE | ID: mdl-38865319

ABSTRACT

INTRODUCTION: In low-resource settings, magnesium sulphate (MgSO4) for preeclampsia is administered majorly through an injection into the gluteal muscles 4-hourly for 24 hours. The repeated injections are very painful and may lead to infection, abscess formation, and reduced compliance. OBJECTIVE: To determine the acceptability of Springfusor® pump for the administration of Magnesium Sulphate in preeclampsia and eclampsia. DESIGN: Randomized Open Label Clinical Trial. METHODS: The study was conducted at Kawempe National Referral Hospital. Eligible women had a systolic blood pressure of ≥140mmHg and or diastolic blood pressure >90mmHg, proteinuria ≥+1, and the physician's decision to start on MgSO4. Four-hundred-ninety-six participants were randomized to a Springfusor® pump group (n = 248) or control (standard of care) (n = 248) administration of MgSO4. Intervention group had a loading dose (4gm of 50% MgSO4 intravenously over 20 minutes) and maintenance therapy (1gm of 50% MgSO4 intravenously per hour for 24 hours) administered using the Springfusor®. The standard of care (SOC) group received a loading dose of 4gm of 20% MgSO4 IV over 15-20 minutes, followed by 10gm of 50% MgSO4 intramuscular (5gm in each buttock) and a maintenance dose of 5gm of 50% MgSO4 was administered IM every 4 hours for 24 hours. Both arms received the rest of the care for preeclampsia/eclampsia as per the hospital guidelines. Acceptability of the method of administration was assessed using a Likert scale (1-5; 1 and 2: acceptable and 3-5: unacceptable). Pain at the site of MgSO4 administration was assessed using a Visual Analogue Scale 1-7, (1 minimal pain and 7 worst pain). Comparisons were assessed with the Chi-square test, Mann Whitney-Wilcoxon test, and Students' t-test. RESULTS: Intervention arm; was more acceptable than the standard of care arm, (95.3% vs70.3%; p<0.001), had a lower median pain score, (2(CI: 2-2), vs 4(CI: 4-5) p<0.001), and fewer side effects. Maternal mortality was comparable between groups (0.8% in the intervention arm vs 1.2% in the IM arm). TRIAL REGISTRATION: Trial No PACTR201712002887266 (https://pactr.samrc.ac.za/).


Subject(s)
Eclampsia , Magnesium Sulfate , Pre-Eclampsia , Standard of Care , Humans , Magnesium Sulfate/administration & dosage , Magnesium Sulfate/therapeutic use , Female , Pre-Eclampsia/drug therapy , Pregnancy , Eclampsia/drug therapy , Adult , Young Adult , Injections, Intramuscular
20.
BMC Womens Health ; 24(1): 323, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38835013

ABSTRACT

BACKGROUND: A retrospective cohort study was conducted to collect the data of pregnant women who received hospital delivery in Hangzhou Women's Hospital from January 2018 to December 2020, and who participated in the second trimester (15-20+6 weeks) of free beta human chorionic gonadotropin (free ß-hCG). And the study was conducted to explore the relationship between maternal serum free ß-hCG and adverse pregnancy outcomes (APO). METHODS: We retrospectively analyzed the clinical data of 1,978 women in the elevated maternal serum free ß-hCG group (free ß-hCG ≥ 2.50 multiples of the median, MoM) and 20,767 women in the normal group (0.25 MoM ≤ free ß-hCG < 2.50 MoM) from a total of 22,745 singleton pregnancies, and modified Poisson regression analysis was used to calculate risk ratios (RRs) and 95% confidence intervals (CI) of the two groups. RESULTS: The gravidity and parity in the elevated free ß-hCG group were lower, and the differences between the groups were statistically significant (all, P < 0.05). The risks of polyhydramnios, preeclampsia, and hyperlipidemia, were increased in women with elevated free ß-hCG levels (RRs: 1.996, 95% CI: 1.322-3.014; 1.469, 95% CI: 1.130-1.911 and 1.257, 95% CI: 1.029-1.535, respectively, all P < 0.05), intrauterine growth restriction (IUGR) and female infants were also likely to happen (RRs = 1.641, 95% CI: 1.103-2.443 and 1.101, 95% CI: 1.011-1.198, both P < 0.05). Additionally, there was an association between elevated AFP and free ß-hCG levels in second-trimester (RR = 1.211, 95% CI: 1.121-1.307, P < 0.001). CONCLUSIONS: APOs, such as polyhydramnios, preeclampsia, and hyperlipidemia, were increased risks of elevated free ß-hCG levels, IUGR and female infants were also likely to happen. Furthermore, there was an association between elevated AFP levels and elevated free ß-hCG levels in second-trimester. We recommend prenatal monitoring according to the elevated maternal serum free ß-hCG level and the occurrence of APO.


Subject(s)
Chorionic Gonadotropin, beta Subunit, Human , Pregnancy Outcome , Pregnancy Trimester, Second , Humans , Pregnancy , Female , Retrospective Studies , Pregnancy Trimester, Second/blood , Adult , Pregnancy Outcome/epidemiology , Chorionic Gonadotropin, beta Subunit, Human/blood , Pregnancy Complications/blood , Pregnancy Complications/epidemiology , China/epidemiology , Pre-Eclampsia/blood , Pre-Eclampsia/epidemiology , Cohort Studies , Polyhydramnios/blood , Polyhydramnios/epidemiology , Chorionic Gonadotropin/blood , Hyperlipidemias/blood , Hyperlipidemias/epidemiology
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