Small RNAs in the pathogenesis of preeclampsia.

Preeclampsia is a major contributor to maternal and fetal morbidity and mortality. The disorder can be classified into early- and late-onset subtypes, both of which evolve in two stages. The first stage comprises the development of pre-clinical, utero-placental malperfusion. Early and late utero-placental malperfusion have different causes and time courses. Early-onset preeclampsia (20 % of cases) is driven by dysfunctional placentation in the first half of pregnancy. In late-onset preeclampsia (80 % of cases), malperfusion is a consequence of placental compression within the confines of a limited uterine cavity. In both subtypes, the malperfused placenta releases stress signals into the maternal circulation. These stress signals trigger onset of the clinical syndrome (the second stage). Small RNA molecules, which are implicated in cellular stress responses in general, may be involved at different stages. Micro RNAs contribute to abnormal trophoblast invasion, immune dysregulation, angiogenic imbalance, and syncytiotrophoblast-derived extracellular vesicle signalling in preeclampsia. Transfer RNA fragments are placental signals known to be specifically involved in cell stress responses. Disorder-specific differences in small nucleolar RNAs and piwi-interacting RNAs have also been reported. Here, we summarise key small RNA advances in preeclampsia pathogenesis. We propose that existing small RNA classifications are unhelpful and that non-biased assessment of RNA expression, incorporation of non-annotated molecules and consideration of chemical modifications to RNAs may be important in elucidating preeclampsia pathogenesis.

The sFlt-1/PlGF-ratio and the risk of preeclampsia-related adverse outcomes in subsequent pregnancies with signs and symptoms of a preeclampsia.

OBJECTIVES: This study characterizes the outcome of two subsequent pregnancies with suspected preeclampsia (PE). We investigated the diagnostic accuracy of clinical signs, Doppler examinations, and the soluble fms-like tyrosine kinase-1 (sFlt-1) to placental growth factor (PlGF)-ratio to predict PE-related adverse outcomes (AO). The sFlt-1/PlGF-ratio of the first pregnancy was compared to the outcome of the subsequent pregnancy. STUDY DESIGN: A total of 1928 patients at risk for preeclampsia were screened, of them 1117 were eligible for inclusion. Of these, 84 women presented with suspected PE in two subsequent pregnancies. OUTCOME MEASURES: Diagnostic accuracy of clinical markers was assessed. Associations between the sFlt-1/PlGF-ratio in the first and the odds of an AO in the subsequent pregnancy were investigated with logistic regression. RESULTS: The prevalence of AOs decreased from 27.4 % in the first to 17.9 % in the second pregnancy. Comparison of the accuracy of the different clinical markers for an AO showed a high specificity for an sFlt-1/PlGF-ratio at the cut-off of ≥ 85 in both pregnancies (81.3 %, 95 % CI 63.6-92.8 vs 92.6 %,95 % CI 83.7-97.6), but a lower sensitivity in the second pregnancy (92.9 %, 95 % CI 66.1-99.8 vs 33.3%, 95 % CI 11.8-61.6). An elevated sFlt-1/PlGF-ratio in the first did not increase the odds of an AO in the subsequent pregnancy. CONCLUSIONS: The prevalence of AOs decreases in subsequent pregnancies. Our finding that the sFlt-1/PlGF-ratio of the first was not related to the outcome of the subsequent pregnancy suggests that angiogenic markers are only a within-pregnancy short-term tool to assess AOs.

Inflammatory markers in relation to maternal lifestyle and adverse pregnancy outcomes in twin pregnancies.

It is well known that inflammatory markers play an important role in the development and maintenance of healthy pregnancies. However, the literature regarding inflammation in relation to lifestyle and adverse pregnancy outcomes in twin pregnancies is remarkably uncovered. Therefore, this study aimed at evaluating the concentration of inflammatory markers in dried capillary blood spot samples from 523 women with twin pregnancies, included at a median gestational age of 21+1 weeks. The relationship between inflammatory markers and maternal lifestyle (current smoking status and pre-pregnancy body mass index) in addition to adverse pregnancy outcomes (preeclampsia, gestational diabetes mellitus, and small for gestational age) was analyzed. The study showed that active smoking at inclusion was associated with an elevated concentration of interleukin-8. Furthermore, maternal obesity was associated with an elevated concentration of C-reactive protein and monocyte chemoattractant protein-1. Analysis of the data showed no statistically significant variations in the concentration of the assessed inflammatory markers for neither preeclampsia, gestational diabetes mellitus, nor small for gestational age. The current study promotes future research on the pathophysiology of twin pregnancies in relation to adverse pregnancy outcomes, as the literature within the area remains scarce.

Pre-eclampsia challenges and care in low and middle-income countries: Understanding diagnosis, management, and health impacts in remote and developing regions.

As an example of a low- and middle-income country (LMIC), India ranks pre-eclampsia among the top three causes of maternal mortality, following haemorrhage and infections. It is one of the primary concerns for maternal and perinatal health in LMICs. Many LMICs lack clear consensus and guidelines for the prevention, diagnosis, and management of hypertensive disorders in pregnancy, including pre-eclampsia. The International Society for the Study of Hypertension in Pregnancy 2021 guidelines address LMIC applications, offering customisable solutions. Atypical presentations of pre-eclampsia contribute to diagnostic delays, resulting in additional adverse maternal and perinatal outcomes. Implementing management strategies faces challenges in both urban and rural settings. Adapting global research involving local populations is imperative, with the potential for cost-effective adoption of international guidelines. Prevention, early diagnosis, and education dissemination are essential, involving healthcare providers and advocacy initiatives. Encouraging government investment in pre-eclampsia management as a public health initiative is important. This article explores socio-economic, cultural, and legislative factors influencing the management of pre-eclampsia in LMICs, addressing emerging challenges and potential partnerships for healthcare provision.

Risk prediction for preeclampsia in CKD patients: development of a model in a retrospective cohort.

BACKGROUND: Chronic kidney disease (CKD) may affect women of childbearing age and may lead to substantial maternal and foetal morbidity and mortality in pregnancy. There is a lack of prediction models for  preeclampsia and adverse pregnancy outcomes in pregnant women with CKD. This study aimed to create a prediction nomogram for these issues. METHODS: This retrospective cohort study included clinical data from 627 women with CKD and their 627 pregnancies at Peking University First Hospital between January 1, 2009, and December 31, 2022. Multivariate logistic regression analysis was conducted to identify independent prognostic factors and develop a nomogram for predicting the occurrence of preeclampsia. The identified risk factors were utilised to construct the nomogram, which was subsequently internally validated using receiver operating characteristic (ROC) analysis and calibration curve assessment. RESULTS: According to our multivariate analysis, age, blood urea nitrogen (BUN), serum creatinine (Scr), mean arterial pressure (MAP), 24-h proteinuria, and CKD stage were identified as predictors of preeclampsia. Additionally, Scr, MAP, BUN, and 24-h proteinuria were found to be predictors of adverse pregnancy outcomes. The nomogram for predicting preeclampsia had an area under the ROC curve of 0.910, while the nomogram for predicting adverse pregnancy outcomes had an area under the ROC curve of 0.906. Both models demonstrated excellent discriminatory ability. CONCLUSIONS: A nomogram based on 24-h proteinuria, serum creatinine, serum urea and age, and MAP allows predicting the occurrence of preeclampsia and other adverse pregnancy-related outcomes in CKD patients.

Maternal angiogenic factor disruptions prior to clinical diagnosis of preeclampsia: insights from the REVAMP study.

Preeclampsia is characterized by impaired angiogenesis and assessment of angiogenic factors can play a crucial role in the early diagnosis of preeclampsia. The current study reports the levels of angiogenic factors longitudinally from early pregnancy in women with preeclampsia and in the subtypes of preeclampsia, to identify their role in early prediction of preeclampsia. A total of 1154 women with singleton pregnancies were recruited in early pregnancy from 2 hospitals. Blood samples were collected, plasma samples were separated and stored at four time points across gestation: V1 = 11-14 weeks, V2 = 18-22 weeks, V3 = 26-28 weeks, and V4 = at delivery. The current study includes a total of 108 women developed preeclampsia (PE), and 216 matched controls. Angiogenic factors were estimated using commercially available ELISA kits. Receiver operating characteristic (ROC) curves were used to evaluate the potential diagnostic value in the prediction of PE. Lower levels of VEGF, PlGF, and higher levels of sEng and sEng/PlGF ratio (p < 0.05 for all) predate clinical diagnosis in women with preeclampsia. sEng levels and sEng/PlGF ratio showed significant correlation with odds of preeclampsia at all the timepoints. This study identifies a cut off of 33.5 for sFlt-1/PlGF and 25.9 for sEng/PlGF for prediction of early onset preeclampsia. This study reports various angiogenic factors serially across gestation in a general population to identify women at risk of developing preeclampsia and its subtypes. The study also reports a potential biomarker and a pragmatic window for estimation of angiogenic markers to identify women at risk.

Alterations of Placental Sodium in Preeclampsia: Trophoblast Responses.

BACKGROUND: Evidence suggests that increasing salt intake in pregnancy lowers blood pressure, protecting against preeclampsia. We hypothesized that sodium (Na+) evokes beneficial placental signals that are disrupted in preeclampsia. METHODS: Blood and urine were collected from nonpregnant women of reproductive age (n=26) and pregnant women with (n=50) and without (n=55) preeclampsia, along with placental biopsies. Human trophoblast cell lines and primary human trophoblasts were cultured with varying Na+ concentrations. RESULTS: Women with preeclampsia had reduced placental and urinary Na+ concentrations, yet increased urinary angiotensinogen and reduced active renin, aldosterone concentrations, and osmotic response signal TonEBP (tonicity-responsive enhancer binding protein) expression. In trophoblast cell cultures, TonEBP was consistently increased upon augmented Na+ exposure. Mechanistically, inhibiting Na+/K+-ATPase or adding mannitol evoked the TonEBP response, whereas inhibition of cytoskeletal signaling abolished it. CONCLUSIONS: Enhanced Na+ availability induced osmotic gradient-dependent cytoskeletal signals in trophoblasts, resulting in proangiogenic responses. As placental salt availability is compromised in preeclampsia, adverse systemic responses are thus conceivable.

The expression of TIM-3 and Gal-9 on macrophages and Hofbauer cells in the placenta of preeclampsia patients.

Preeclampsia is a disorder of pregnancy characterized by endothelial dysfunction, abnormal placentation, systemic inflammation, and altered immune reaction. The aim of this study was to investigate the immune checkpoint molecules TIM-3 and Gal-9 on macrophages and Hofbauer cells (HBC) in the placenta of preeclampsia patients. Immunohistochemistry and Immunofluorescence was used to characterize the expression of the macrophage markers CD68 and CD163, CK7 and the proteins TIM-3 and Gal-9 in the placentas of preeclampsia patients comparing it to the placentas of healthy pregnancies. Double immunofluorescence staining (TIM-3 with CD3/CD19/CD56) was used to analyze the TIM-3 expression on other immune cells (T cells, B cells, NK cells) within the chorionic villi. The expression of TIM-3 on decidual macrophages did not significantly differ between the preeclamptic and the control group (p = 0.487). When looking at the different offspring we saw an upregulation of TIM-3 expression on decidual macrophages in preeclamptic placentas with female offspring (p = 0.049). On Hofbauer cells within the chorionic villi, the TIM-3 expression was significantly downregulated in preeclamptic cases without a sex-specific difference (p < 0.001). Looking at the protein Gal-9 the expression was proven to be downregulated both, on decidual macrophages (p = 0.003) and on Hofbauer cells (p = 0.002) within preeclamptic placentas compared to healthy controls. This was only significant in male offspring (p < 0.001 and p = 0.013) but not in female offspring (p = 0.360 and p = 0.068). While TIM-3 expression within the extravillious trophoblast and the syncytiotrophoblast was significantly downregulated (p < 0.001 and p = 0.012) in preeclampsia, the expression of Gal-9 was upregulated in (p < 0.001 and p < 0.001) compared to healthy controls. The local variations of the immune checkpoint molecules TIM-3 and Gal-9 in the placenta may contribute to the inflammation observed in preeclamptic patients. It could therefore contribute to the pathogenesis and be an important target in the treatment of preeclampsia.

Feto-maternal indicators of cardiac dysfunction as a justification for the cardiac origins for pre-eclampsia.

While the pathophysiology of pre-eclampsia has been postulated as being secondary to placental dysfunction, a cardiac origin has more recently been proposed. Although an association between fetal congenital cardiovascular disease and pre-eclampsia has been demonstrated, no precise pathophysiologic mechanism for this association has been described. This review highlights the current biophysical (including echocardiography and Doppler indices) and biochemical (including proteomic, metabolomic and genetic/transcriptomic) markers of cardiac dysfunction that have been investigated in maternal and fetal cardiac disease and their overlap with predictors of pre-eclampsia.   Common pathways of inflammatory and anti-angiogenesis imbalance, endothelial damage, and oxidative stress have been demonstrated in both cardiovascular disease and pre-eclampsia and further investigation into these pathways could help to elucidate the common pathophysiologic mechanisms linking these disorders.

Metabolic Theory of Preeclampsia: Implications for Maternal Cardiovascular Health.

Preeclampsia (PE) is a multisystemic disorder of pregnancy that not only causes perinatal mortality and morbidity but also has a long-term toll on the maternal and fetal cardiovascular system. Women diagnosed with PE are at greater risk for the subsequent development of hypertension, ischemic heart disease, cardiomyopathy, cerebral edema, seizures, and end-stage renal disease. Although PE is considered heterogeneous, inefficient extravillous trophoblast migration leading to deficient spiral artery remodeling and increased uteroplacental vascular resistance is the likely initiation of the disease. The principal pathophysiology is placental hypoxia, causing subsequent oxidative stress, leading to mitochondrial dysfunction, mitophagy, and immunological imbalance. The damage imposed on the placenta in turn results in the 'stress response' categorized by the dysfunctional release of vasoactive components including oxidative stressors, pro-inflammatory factors, and cytokines into the maternal circulation. These bioactive factors have deleterious effects on systemic endothelial cells and coagulation leading to generalized vascular dysfunction and hypercoagulability. A better understanding of these metabolic factors may lead to novel therapeutic approaches to prevent and treat this multisystemic disorder. In this review, we connect the hypoxic-oxidative stress and inflammation involved in the pathophysiology of PE to the resulting persistent cardiovascular complications in preeclamptic patients.

Massive ascites following spontaneous vaginal delivery in a woman with preeclampsia-a diagnostic and management challenges in a low resource country: A case report.

INTRODUCTION AND IMPORTANCE: Hypertensive disorders of pregnancy, including preeclampsia, causes major pregnancy associated morbidity and mortality. Massive ascites is a rare complication in a severe preeclampsia. This case report high lights the importance of obstetrician being aware of such complications of severe preeclampsia, and avoid non-therapeutic interventions such as exploratory laparotomy. CASE PRESENTATION: A 39-year-old woman from remote village of Bhutan with severe preeclampsia had spontaneous vaginal delivery in the ambulance at 34+6 weeks of gestation enroute to a tertiary care hospital. In the postpartum period, she had a massive ascites, and she underwent exploratory laparotomy. DISCUSSION: Ascites in severe preeclampsia is a rare complication. Diagnosis and management of such a rare condition is challenging in a resource constraint setting. In addition, prevalence of tuberculosis and gynecological malignancies in our setting prompts obstetricians to perform an invasive procedure such as exploratory laparotomy in view of excluding these conditions. CONCLUSION: This case report highlights the importance of obstetricians to be aware of the possibility of ascites in preeclampsia which may be managed medically, without the need for surgical interventions.

Evaluation of the diagnostic value of the HALP score, uric acid value, and uric acid-creatinine ratio in preeclampsia.

OBJECTIVE: In this study, we aimed to evaluate the diagnostic value of the HALP score, serum uric acid value, and uric acid-creatinine ratio, which are inflammatory markers, in the diagnosis of preeclampsia (PE). MATERIALS AND METHODS: One hundred sixty-six pregnant women who met the inclusion and exclusion criteria were included in the study. They were divided into two groups: 81 pregnant women diagnosed with PE (PE group) and 85 pregnant women with healthy pregnancies (control group). Demographic and obstetric stories of the groups; weeks of pregnancy at diagnosis; hematological and biochemical parameters; hemoglobin, albumin, lymphocyte, and platelet (HALP) score and serum uric acid-creatinine ratio (sUA/sCr); and the results of the newborns were recorded and compared between groups. RESULTS: There was no significant difference between the groups in terms of age, gravidity, parity, and body mass index (P values = 0.533, 0.188, 0.085, 0.915, resp.). Mean gestational age, mean birth weight, 1st and 5th minute Apgar scores, and mean umbilical cord pH values were lower in the PE group compared to the control group (P values = 0.0001 for all). Percentage of NICU admissions was higher in the PE group (P = 0.0001). HALP score of the PE group was significantly lower than the control group (2.2 vs. 3.2; P = 0.0001). Uric acid and sUA/sCr ratios were significantly higher in the PE group compared to the control group (for uric acid, 6.2 ± 1.7 vs. 4.5 ± 1.2; P = 0.0001; for sUA/sCr, 12.0 ± 4.0 vs. 9.9 ± 3.1; P = 0.0001). In diagnosing PE, serum uric acid had a sensitivity of 82.7% at values of 4.7 and above, 58% sensitivity at values of sUA/sCr ratio of 10.9 and above, and 3.7% sensitivity at HALP score values of 6.6 and above (P values = 0.0001, 0.001, 0.001, resp.). CONCLUSION: In our study, we found that the HALP score in PE was significantly lower than in healthy controls, and the uric acid value and sUA/sCr ratios were significantly higher. Diagnostic value of the serum uric acid value and then the sUA/sCr ratio were higher in PE. However, we found that the HALP score was insufficient for diagnosing PE.

Preeclampsia and neonatal outcomes in pregnancies with maternal congenital heart disease: A nationwide cohort study from Norway.

INTRODUCTION: The prevalence of congenital heart disease (CHD) among women of reproductive age is rising. We aimed to investigate the risk of preeclampsia and adverse neonatal outcomes in pregnancies of mothers with CHD compared to pregnancies of mothers without heart disease. MATERIAL AND METHODS: In a nationwide cohort of pregnancies in Norway 1994-2014, we retrieved information on maternal heart disease, the course of pregnancy, and neonatal outcomes from national registries. Comparing pregnancies with maternal CHD to pregnancies without maternal heart disease, we used Cox regression to estimate the adjusted hazard ratio (aHR) for preeclampsia and log-binomial regression to estimate the adjusted risk ratio (aRR) for adverse neonatal outcomes. The estimates were adjusted for maternal age and year of childbirth and presented with 95% confidence intervals (CIs). RESULTS: Among 1 218 452 pregnancies, 2425 had mild maternal CHD, and 603 had moderate/severe CHD. Compared to pregnancies without maternal heart disease, the risk of preeclampsia was increased in pregnancies with mild and moderate/severe maternal CHD (aHR1.37, 95% CI 1.14-1.65 and aHR 1.62, 95% CI 1.13-2.32). The risk of preterm birth was increased in pregnancies with mild maternal CHD (aRR 1.33, 95% CI 1.15-1.54) and further increased with moderate/severe CHD (aRR 2.49, 95% CI 2.03-3.07). Maternal CHD was associated with elevated risks of both spontaneous and iatrogenic preterm birth. The risk of infants small-for-gestational-age was slightly increased with mild maternal CHD (aRR 1.12, 95% CI 1.00-1.26) and increased with moderate/severe CHD (aRR 1.63, 95% CI 1.36-1.95). The prevalence of stillbirth was 3.9 per 1000 pregnancies without maternal heart disease, 5.6 per 1000 with mild maternal CHD, and 6.8 per 1000 with moderate/severe maternal CHD. Still, there were too few cases to report a significant difference. There were no maternal deaths in women with CHD. CONCLUSIONS: Moderate/severe maternal CHD in pregnancy was associated with increased risks of preeclampsia, preterm birth, and infants small-for-gestational-age. Mild maternal CHD was associated with less increased risks. For women with moderate/severe CHD, their risk of preeclampsia and adverse neonatal outcomes should be evaluated together with their cardiac risk in pregnancy, and follow-up in pregnancy should be ascertained.

Connecting the Dots: Exploring the Interplay Between Preeclampsia and Peripartum Cardiomyopathy.

Preeclampsia and peripartum cardiomyopathy (PPCM) are significant obstetric problems that can arise during or after pregnancy. Both are known to be causes of maternal mortality and morbidity. Several recent studies have suggested a link between preeclampsia and the pathophysiology of PPCM. However, the common thread that connects the two has yet to be thoroughly and fully articulated. Here, we investigate the complex dynamics of preeclampsia and PPCM in this review. Our analysis focuses mainly on inflammatory and immunological responses, endothelial dysfunction as a shared pathway, and potential genetic predisposition to both diseases. To begin, we will look at how excessive inflammatory and immunological responses can lead to clinical symptoms of both illnesses, emphasizing the role of proinflammatory cytokines and immune cells in modifying vascular and tissue responses. Second, we consider endothelial dysfunction to be a crucial point at which endothelial damage and activation contribute to pathogenesis through increased vascular permeability, vascular dysfunction, and thrombus formation. Finally, we examine recent information suggesting genetic predispositions to preeclampsia and PPCM, such as genetic variants in genes involved in the management of blood pressure, the inflammatory response, and heart structural integrity. With this synergistic study, we seek to encourage more research and creative therapy solutions by emphasizing the need for an interdisciplinary approach to understanding and managing the connection between preeclampsia and PPCM.

Association of NLRP3 and IL-4 VNTR polymorphisms and genetic susceptibility to preeclampsia: A case-control study.

INTRODUCTION: Abnormalities in the maternal immune system and insufficient gestational immune tolerance may significantly contribute to the development of preeclampsia (PE). The NLR family pyrin domain containing 3 (NLRP3) functions as a pattern recognition receptor that identifies pathogen-associated molecular patterns. Interleukin-4 (IL-4) is a potent anti-inflammatory cytokine that modulates the immune response. Therefore, this study aims to elucidate the impact of NLRP3 and IL-4 variable number of tandem repeats (VNTR) polymorphisms on susceptibility to PE. MATERIALS AND METHODS: A total of 1,018 patients with PE and 1,007 normal pregnant women were recruited as the case group and the control group, respectively. Peripheral blood DNA was extracted, and NLRP3 and IL-4 VNTR polymorphisms were genotyped using polymerase chain reaction and gel electrophoresis. Genotypes and allele frequencies of pregnant women were assessed in both cohorts. RESULTS: The NLRP3 VNTR 9-7 genotype in the PE group was significantly lower than that in the control group, but 9 and 14 allele frequencies were significantly higher in patients with PE. Individuals with IL-4 VNTR genotypes 1-2 had a lower risk of PE than controls, and the IL-4 VNTR 2 allele frequency was significantly lower in patients with PE. CONCLUSIONS: This study, the first of its kind in the literature, evaluates the impact of NLRP3 VNTR and IL-4 VNTR polymorphisms on PE, revealing a significant correlation with PE susceptibility. This investigation contributes to understanding the pathogenesis of PE and provides a reference point for developing strategies to prevent and treat the disease in the future.

A prediction model for stillbirth based on first trimester pre-eclampsia combined screening.

OBJECTIVE: To evaluate the accuracy of combined models of maternal biophysical factors, ultrasound, and biochemical markers for predicting stillbirths. METHODS: A retrospective cohort study of pregnant women undergoing first-trimester pre-eclampsia screening at 11-13 gestational weeks was conducted. Maternal characteristics and history, mean arterial pressure (MAP) measurement, uterine artery pulsatility index (UtA-PI) ultrasound, maternal ophthalmic peak ratio Doppler, and placental growth factor (PlGF) serum were collected during the visit. Stillbirth was classified as placental dysfunction-related when it occurred with pre-eclampsia or birth weight <10th percentile. Combined prediction models were developed from significant variables in stillbirths, placental dysfunction-related, and controls. We used the area under the receiver-operating-characteristics curve (AUC), sensitivity, and specificity based on a specific cutoff to evaluate the model's predictive performance by measuring the capacity to distinguish between stillbirths and live births. RESULTS: There were 13 (0.79%) cases of stillbirth in 1643 women included in the analysis. The combination of maternal factors, MAP, UtA-PI, and PlGF, significantly contributed to the prediction of stillbirth. This model was a good predictor for all (including controls) types of stillbirth (AUC 0.879, 95% CI: 0.799-0.959, sensitivity of 99.3%, specificity of 38.5%), and an excellent predictor for placental dysfunction-related stillbirth (AUC 0.984, 95% CI: 0.960-1.000, sensitivity of 98.5, specificity of 85.7). CONCLUSION: Screening at 11-13 weeks' gestation by combining maternal factors, MAP, UtA-PI, and PlGF, can predict a high proportion of stillbirths. Our model has good accuracy for predicting stillbirths, predominantly placental dysfunction-related stillbirths.

Circ_0007611 modulates the miR-34c-5p/LPAR2 cascade to suppress proliferation and enhance apoptosis of HTR-8/SVneo cells.

INTRODUCTION: The aberrant biological behaviors of trophoblast cells actively take part in the pathogenesis of preeclampsia (PE). Herein, we defined the action of the circular RNA (circRNA) circ_0007611 on trophoblast cell apoptosis and growth to understand its role in PE. METHODS: Expression of circ_0007611, miR-34c-5p and lysophosphatidic acid receptor 2 (LPAR2) mRNA was analyzed by qPCR. LPAR2 protein was determined by western blotting. Cell proliferation was analyzed by EdU assay. We assessed apoptosis through flow cytometry and analysis of caspase3 activity and apoptosis-related marker proteins. The binding of miR-34c-5p and circ_0007611 or LPAR2 was verified by dual-luciferase and pull-down assays. RESULTS: Circ_0007611 and LPAR2 levels were augmented, while miR-34c-5p was diminished in blood samples of PE. Circ_0007611 deficiency repressed cell apoptosis and enhanced the growth of HTR-8/SVneo cells. Circ_0007611 interacted with miR-34c-5p, and miR-34c-5p depletion reversed circ_0007611 deficiency-induced HTR-8/SVneo cell apoptotic inhibition and growth enhancement. MiR-34c-5p targeted LPAR2, and circ_0007611 affected LPAR2 expression via miR-34c-5p competition. Circ_0007611 deficiency-induced HHTR-8/SVneo cell apoptotic inhibition and growth enhancement were also counteracted by LPAR2 overexpression. DISCUSSION: Circ_0007611 modulates the miR-34c-5p/LPAR2 cascade to enhance apoptosis and inhibit proliferation in HTR-8/SVneo cells, thereby contributing to the progression of PE.

A Comparison of Obstetric Outcomes in Antiphospholipid Syndrome Among Pregnant Women With Systemic Lupus Erythematosus.

Objective The aim of this study was to evaluate the maternal and perinatal outcomes in systemic lupus erythematosus (SLE) women with antiphospholipid syndrome (APS). Methods This retrospective case-control study was conducted among pregnant women with SLE with and without APS. Group A included SLE patients with APS, whereas group B included pregnant SLE women without APS. Data were expressed as mean ± standard deviation (SD). Frequency and percentage were computed for categorical data. The chi-square test was used to analyze the difference between categorical data. Results Out of 125 cases of SLE, APS was found in 72 (57.6%) women. Almost 95.8% of patients were on treatment (aspirin and enoxaparin) in group A. Preterm delivery (31.89±7.36 versus 34.46±4.97; p=0.021) and termination of pregnancy (18.1% [13/72] versus 5.7% [3/53]; p=0.04) were statistically significant in group A. Among these terminations, second-trimester intrauterine death is found to be more in group A (SLE with APS) (16.7% [12/72]) as compared to group B (SLE without APS) (5.7% [3/53]) with a p-value of 0.05. Perinatal outcomes including NICU admissions (39% [23/59] versus 24% [12/50]; p=0.071) and neonatal death (12.3% [7/57]; p=0.015) were also found to be statistically significant between the two groups. Conclusion APS with SLE is associated with adverse pregnancy outcomes such as preterm birth, termination of pregnancy due to second-trimester fetal loss, more NICU admission, and neonatal deaths when compared to the control group. Hence, pregnancies with APS with SLE require vigilant monitoring and frequent follow-ups to ensure a positive pregnancy outcome.

Significance of the sFlt-1/PlGF Ratio in Certain Cohorts - What Needs to be Considered?

The sFlt-1/PlGF ratio is an established tool in clinical practice, where it is part of a diagnostic algorithm and informs the prognosis of preeclampsia (PE). Maternal and gestational comorbidities can affect the performance of the sFlt-1/PlGF ratio and its constituent elements, and a good understanding of the potential pitfalls is required. The objective of this paper was to provide a current narrative review of the literature on the diagnostic and predictive performance of the sFlt-1/PlGF ratio in specific patient cohorts. Potential factors which can negatively affect the clinical interpretability and applicability of the sFlt-1/PlGF ratio include chronic kidney disease, twin pregnancy, and maternal obesity. Pathophysiological mechanisms related to these factors and disorders can result in different concentrations of sFlt-1 and/or PlGF in maternal blood, meaning that the use of standard cut-off values in specific cohorts can lead to errors. To what extent the cut-off values should be adapted in certain patient cohorts can only be clarified in large prospective cohort studies. This applies to the use of the ratio both for diagnosis and prognosis.