Circulating immune cells and apolipoprotein A mediation: a Mendelian randomization study on hypertensive disorder of pregnancy.

Background: Studies using observational epidemiology have indicated that inflammation and immunological dysregulation are important contributors to placental and renal failure, which ultimately results in maternal hypertension. The potential causal relationships between the immunophenotypes and hypertensive disorder of pregnancy (HDP) are yet unclear. Methods: We conducted two-sample Mendelian randomization (MR) analyses to thoroughly examine the relationship between immunophenotypes and HDP. The GWAS data on immunological traits was taken from public catalog for 731 immunophenotypes and the summarized GWAS data in 4 types of HDP were retrieved from FinnGen database. The link between immune cell traits and HDP was examined through our study methodology, taking into account both direct relationships and mediation effects of apolipoprotein A (apoA). The inverse variance weighted (IVW) method served as the main analysis, while sensitivity analysis was carried out as a supplement. Results: We identified 14 highly correlative immunophenotypes and 104 suggestive possible factors after investigating genetically predicted immunophenotype biomarkers. According to the IVW analysis, there was a strong correlation between HDP and HLA DR on DC and plasmacytoid DC. Reverse MR analysis showed that there was no statistically significant effect of HDP on immune cells in our investigation. Mediation analysis confirmed that apoA mediates the interaction between HLA DR on DC and HDP. Conclusion: Our results highlight the complex interplay of immunophenotypes, apoA, and HDP. Moreover, the pathophysiological link between HLA DR on DC and HDP was mediated by the level of apoA.

Study of C-reactive Protein Levels in Hypertensive Disorders of Pregnancy.

Introduction Globally, one of the main causes of maternal and perinatal deaths is hypertensive disorders of pregnancy (HDP). Preeclampsia is a pregnancy-specific syndrome characterized by high blood pressure and proteinuria after 20-week gestation. Women who develop preeclampsia are at increased risk for the development of many systemic complications. Materials and methods A cross-sectional study was conducted in the Department of Biochemistry, SHKM, Nuh, Haryana in collaboration with the Department of Obstetrics & Gynecology. 200 study subjects; Group 1: cases - 100 HDP, Group 2: controls - 100 age-matched normotensive pregnant women. The specimen of 3 mL venous blood was collected under aseptic precautions. The data was evaluated using statistical evaluation tools. Result Out of 200 subjects, mean C-reactive protein (CRP) levels were normal in three cases and 35 controls. Minor elevation of CRP was observed in 11 cases and 29 controls (very significant). Moderate elevation of CRP was observed in 61 cases and 36 controls (highly significant). Marked elevation of CRP was observed in 25 cases. Mean CRP levels increased from preeclampsia without severe features (3.9 mg/dL), preeclampsia with severe features (5.2 mg/dL), and eclampsia (12.7 mg/dL) when compared with the respective control group (1.1 mg/dL, 1.16 mg/dL, and 1.2 mg/dL). Conclusion There is a highly significant association between CRP levels and HDP. Additionally, one useful indicator of the severity of preeclampsia is CRP, a measure of systemic inflammation. Elevated CRP levels in mild PE can be used as an indicator of the progress of the disease and early prevention can be done.

NANOG regulate the JAK/STAT3 pathway to promote trophoblast cell migration and epithelial-mesenchymal transition (EMT) in hypertensive disorders of pregnancy (HDP) through protein interaction with CDK1.

PROBLEM: Hypertensive disorders of pregnancy (HDP) are a common pregnancy disease. NANOG and Cyclin-dependent kinase 1 (CDK1) are essential for regulating the function of cell proliferation and apoptosis. However, the mechanism of action in HDP is yet unclear. METHOD: The microarray dataset GSE6573 was downloaded from the GEO database. Emt-related gene set was downloaded from Epithelial-Mesenchymal Transition gene database 2.0 were screened differentially expressed genes by bioinformatics analysis. Pathway Commons and Scansite 4.0 databases were used to predict the interaction between proteins. Placental tissue samples were collected from HDP patients and patients with uneventful pregnancies. RT-qPCR, Western blot and immunohistochemistry were used to detect the expression of NANOG, CDK1, MMP-2, MMP-9, EMT markers and the JAK/STAT3 pathway proteins. Transfection NANOG overexpression/knockdown, and CDK1 knockdown into the human chorionic trophoblast cells (HTR-8/Svneo). CCK-8, Transwell and Wound-healing assay were used to evaluate cell proliferation, invasion and migration. CO-IP and GST pull-down assays were used to confirm the protein interaction. RESULTS: A total obtained seven EMT-related differentially expressed genes, wherein NANOG, NODAL and LIN28A had protein interaction. In the HDP patients' tissue found that NANOG and CDK1 had lower expression. NANOG overexpression promoted HTR-8/Svneo proliferation, migration and EMT, while NANOG knockdown had the opposite effect. Further a protein interaction between STAT3 and CDK1 with NANOG. NANOG overexpression downregulated the JAK/STAT3 pathway to promote HTR-8/Svneo proliferation, migration and EMT, which was reversed by CDK1 knockdown. CONCLUSIONS: NANOG downregulated the JAK/STAT3 pathway to promote trophoblast cell proliferation, migration and EMT through protein interaction with CDK1.

Posterior Reversible Encephalopathy Syndrome in a Late Postpartum Patient With a Rare Complication of Subarachnoid Hemorrhage.

Posterior reversible encephalopathy syndrome (PRES) is considered a neuroclinical syndrome of headache, confusion, visual changes, and seizures associated with neuroimaging findings of posterior cerebral white matter edema. Although the incidence of the syndrome is largely unknown, this condition is becoming increasingly recognized. The prognosis is generally good with most symptoms resolving within one week and lesions on imaging resolving in two weeks. Death and significant neurological disability have been reported but are relatively rare. In this report, we present a 10-day postpartum patient with an atypical history of headache and seizure-like activity. Neuroimaging revealed findings consistent with PRES as well as a rare complication of subarachnoid hemorrhage. This case highlights the importance of clinicians considering preeclampsia/eclampsia-induced PRES when encountering a postpartum patient with headache and hypertension to further reduce morbidity and mortality in this patient population.

Uterine Artery Doppler Indices as Predictor of Adverse Fetal Outcome in Hypertensive Disorders of Pregnancy: An Observational Study.

Background Hypertensive disorders of pregnancy (HDP) pose significant risks to maternal and fetal health. The utility of Doppler indices in predicting adverse fetal outcomes in HDP patients remains an area of active research. This observational study aimed to assess the correlation between abnormal uterine artery Doppler indices and adverse fetal outcomes in HDP patients. Methods Over a two-year period, we enrolled 138 pregnant women with HDP beyond 28 weeks of gestation and singleton pregnancies. Detailed clinical assessments, laboratory investigations, and Doppler studies of the uterine artery were conducted. The Doppler indices that were assessed included the systolic/diastolic (S/D) ratio, resistance index (RI), and pulsatility index (PI). Adverse fetal outcomes were classified based on appearance, pulse, grimace, activity, and respiration (APGAR) scores, birth weight, NICU admissions, and perinatal deaths. Statistical analyses were performed to evaluate the predictive value of Doppler indices. Results Abnormal uterine artery Doppler indices, specifically an elevated S/D ratio and the presence of a diastolic notch showed a positive correlation with adverse fetal outcomes. However, Doppler indices such as PI and RI did not demonstrate a significant correlation with adverse fetal outcomes in HDP patients. These findings suggest that the S/D ratio and the presence of a diastolic notch in uterine artery Doppler studies hold potential as predictive markers for adverse fetal outcomes in HDP patients. Conclusion Uterine artery Doppler indices, specifically the S/D ratio and the presence of a diastolic notch, appear to be valuable predictors for adverse fetal outcomes in patients with hypertensive disorders of pregnancy. These findings underscore the importance of regular monitoring of uterine artery Doppler flow in the management of HDP to identify pregnancies at higher risk for adverse fetal outcomes.

Obstructive Sleep Apnoea: A Shrouded High-Risk Association for Development of Hypertensive Disorders of Pregnancy.

Background: This objective of this study was to diagnose Obstructive Sleep Apnoea (OSA) in pregnant women using Questionnaire-based methods and to determine any association of Sleep-Disordered Breathing (SDB) with Hypertensive Disorder of Pregnancy (HDP). Additionally, the study aimed to identify factors associated with OSA. Methods: This case-control study was conducted in department of Obstetrics in tertiary care hospital in Delhi. We Identified SDB using Berlin Questionnaire and Modified Stop-Bang Questionnaire in 100 pregnant women with Hypertension and 100 normotensive controls. We compared the groups using appropriate statistical analysis. Results: The mean age of women with HDP (25.46 ± 4.38) was found to be slightly higher than controls (24.13 ± 3.89) (p value-0.02). Sleep apnoea as depicted by the presence of either high-risk STOP Bang or Berlin score was seen more often in hypertensive women in 45% as compared to controls in 8% (p value < 0.001). Higher pre-pregnancy weight (58.58 ± 9.77 vs. 53.0 ± 6.59), higher BMI (24.03 ± 5.89 vs. 20.68 ± 1.49), higher mean neck circumference (14.97 vs. 14.27 inches) weight gain more than 11 kg during pregnancy (55.6% vs. 38.2%) were the high-risk factors more commonly associated with SDB as seen in women with OSA in hypertensive women. On logistic regression analysis, the presence of OSA was singularly responsible for development of Hypertension (Odds Ratio-13.014, 95% CI 5.237-32.337) (p value < 0.001). Conclusion: Gestational hypertension appears to be strongly associated with the presence of obstructive sleep apnoea. The recognition and treatment of OSA during pregnancy may lead to improved outcomes.

The effectiveness of the Congo Red Dot paper test in hypertensive disorders of pregnancy: A systematic review and meta-analysis.

Background: Congo Red Dot Paper Test (CRDPT) appears to be a simple, cost-effective, non-invasive diagnostic tool for hypertensive disorders of pregnancy (HDP). The main objective of the study is to assess the effectiveness of CRDPT in detecting HDP. Methods: This is a systemic review and meta-analysis of published studies on the effectiveness of CRDPT in the detection of HDP. The study was conducted in line with the PRISMA-DTA guidelines. The PICOS framework was used to search for relevant articles using Medline, PubMed, Google Scholar, Web of Science, and the Cochrane Library databases. The articles were screened against a set of inclusion and exclusion criteria and analysed using the Review Manager 5.4 software. Results: A title, abstract and full article screening was conducted on 18,153 potential articles based on the inclusion and exclusion criteria. The screening yielded five articles for meta-analysis. The total number of normotensive pregnant women (n = 3,380) in the included studies was five times higher than the total number of women with pre-eclampsia (n = 535). A difference between the HDP and normotensive group was noted. This is indicated by a significantly decreased in the effectiveness of CRDPT in detecting HDP as compared to normotensive group [Risk Ratio (RR) = 6.32 (2.17, 18.43) p < 0.00001]. The included studies had a high nature of heterogeneity (I 2 = 98%, p < 0.00001) partially due to different study designs included in the analysis and different regions where studies were conducted given that none of these studies were conducted in African countries where HDP is prominent. Conclusions: According to results generated from 5 studies in this meta-analysis, it was found that CRDPT might not be effective in the detection of hypertensive disorder of pregnancy. Moreover, more research, especially in African women where hypertensive disorders of pregnancy are prevalent, are re-quired to ascertain these findings. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021283679, identifier: CRD42021283679.

Umbilical Artery Doppler Indices in Hypertensive Disorders of Pregnancy: Impact on Fetal Outcomes.

Background Hypertensive disorders of pregnancy (HDP) are associated with increased maternal and fetal risks. Doppler ultrasound indices of the umbilical artery have shown promise in predicting adverse fetal outcomes in HDP patients. This observational study investigated the correlation between abnormal umbilical artery Doppler indices and adverse fetal outcomes in HDP patients. Methodology Over a two-year period from 2020 to 2022, in Acharya Vinoba Bhave Rural Hospital, central India, we enrolled 138 pregnant women with HDP beyond 28 weeks of gestation and singleton pregnancies. Comprehensive clinical assessments, laboratory investigations, and Doppler studies of the umbilical artery were performed. Doppler indices assessed included the systolic/diastolic (S/D) ratio, resistance index (RI), and pulsatility index (PI). Adverse fetal outcomes were defined based on birth weight and neonatal intensive care unit admissions. Chi-square or Fisher's exact test was used for analyzing the relationship between qualitative data, while an independent-sample t-test was employed for quantitative data. Results Abnormal umbilical artery Doppler indices, including an elevated S/D ratio, RI, and PI, demonstrated a positive correlation with adverse fetal outcomes in HDP patients. These findings highlight the significance of umbilical artery Doppler indices as reliable indicators for anticipating adverse fetal outcomes in HDP patients. Conclusions Abnormal Doppler indices in the umbilical artery, including an elevated S/D ratio, RI, and PI, appear to be valuable predictors for adverse fetal outcomes in patients with HDP. Monitoring these indices can aid in risk stratification and improve the management of pregnancies complicated by HDP.

Evaluating fetal heart morphology in hypertensive disorders of pregnancy using the fetal heart quantitative technique.

Background: This study sought to explore the clinical application value of fetal heart quantification (HQ) technology in the evaluation of fetal heart morphology in hypertensive disorders of pregnancy (HDP). Methods: Fetal HQ software was used to quantitatively analyze the 4-chamber global sphericity index (GSI) and 24-segment sphericity index (SI) and Z scores of 53 normal fetal hearts (the normal group) and 26 fetal hearts with gestational hypertension (the case group). The normal Z value range was set at -2 to 2. Results: There was a statistically significant difference between the 1-16 and 20-24 segments of the left and right ventricles in the normal group (P<0.05), but there was no statistically significant difference between the 17-19 segments (P>0.05). There was no statistically significant difference in the fetal GSI between the 2 groups (P>0.05). There was no statistically significant difference in the SI of the 24 segments of the fetal left ventricle between the 2 groups (P>0.05). There was no statistically significant difference in the SI between the 1-20 segments of the right ventricle between the 2 groups (P>0.05), but there was a statistically significant difference in the SI between the 21-24 segments (P<0.05). There was no statistically significant difference in the incorrect ratio of the Z value of the GSI between the 2 groups (P>0.05). There was no statistically significant difference in the abnormal rate of the Z value of the SI in each segment of the fetal left ventricle between the 2 groups (P>0.05). There was a significant difference in the abnormal rate of the Z value of the SI in each segment of the fetal right ventricle between the 2 groups (P<0.05). Conclusions: Fetal HQ technology can be used in the quantitative analysis of cardiac morphology in gestational hypertension, and provides a new method for fetal cardiac morphology analysis.

Association between noise exposure during pregnancy and pregnancy complications: A meta-analysis.

Background: Noise exposure has a significant impact on human health. However, the effect of occupational and residential noise on the risk of pregnancy complications was controversial in the literature. This study looked at previous research and performed a meta-analysis to determine how noise exposure during pregnancy affected the risk of pregnancy complications. Methods: Systematic searches were conducted in PubMed, Web of Science, Scopus, Embase, Ovid, and Cochrane, and all relevant studies were included. Two investigators independently evaluated the eligibility of these studies. The risk of bias in each study and the quality and strength of each outcome was evaluated by using the GRADE approach and Navigation Guide. Random effects meta-analysis model was used. Results: The meta-analysis retrieved 1,461 study records and finally included 11 studies. Occupational noise exposure during pregnancy was associated with preeclampsia (RR = 1.07, 95%CI: 1.04, 1.10). Neither occupational nor residential noise exposure was associated with hypertensive disorders of pregnancy (HDP) (RR = 1.10, 95%CI: 0.96, 1.25 and RR = 1.05, 95%CI: 0.98, 1.11) or gestational diabetes mellitus (GDM) (RR = 0.94, 95%CI: 0.88, 1.00 and RR = 1.06, 95%CI: 0.98, 1.16). Further bias analysis showed that the results were reliable. All outcomes were rated as low in quality and inadequate evidence of harmfulness in strength. Conclusions: Occupational noise exposure could increase the risk of preeclampsia, according to the findings. There was no clear evidence of a harmful effect of noise exposure during pregnancy on HDP or GDM.

Kisspeptin in the Prediction of Pregnancy Complications.

Kisspeptin and its receptor are central to reproductive health acting as key regulators of the reproductive endocrine axis in humans. Kisspeptin is most widely recognised as a regulator of gonadotrophin releasing hormone (GnRH) neuronal function. However, recent evidence has demonstrated that kisspeptin and its receptor also play a fundamental role during pregnancy in the regulation of placentation. Kisspeptin is abundantly expressed in syncytiotrophoblasts, and its receptor in both cyto- and syncytio-trophoblasts. Circulating levels of kisspeptin rise dramatically during healthy pregnancy, which have been proposed as having potential as a biomarker of placental function. Indeed, alterations in kisspeptin levels are associated with an increased risk of adverse maternal and foetal complications. This review summarises data evaluating kisspeptin's role as a putative biomarker of pregnancy complications including miscarriage, ectopic pregnancy (EP), preterm birth (PTB), foetal growth restriction (FGR), hypertensive disorders of pregnancy (HDP), pre-eclampsia (PE), gestational diabetes mellitus (GDM), and gestational trophoblastic disease (GTD).

Relationship Between Subclinical Hypothyroidism in Pregnancy and Hypertensive Disorder of Pregnancy: A Systematic Review and Meta-Analysis.

Objective: Studies have shown a high incidence of subclinical hypothyroidism in pregnancy, but the adverse pregnancy outcomes caused by it are not clear. Therefore, we conducted a systematic review and meta-analysis to evaluate the relationship between subclinical hypothyroidism in pregnancy and hypertensive disorders of pregnancy(HDP) to guide clinical practice. Method: We searched the MEDLINE (PubMed), Cochrane Central, EMBASE, Web of Science, and SCOPUS databases and screened all studies evaluating the relationship between subclinical hypothyroidism in pregnancy and hypertensive disorders of pregnancy. Two researchers independently evaluated the quality of all eligible original studies using the Newcastle-Ottawa Scale (NOS). We also performed a meta-analysis using STATA15.1. Sensitivity analyses were also performed by examining the effects of individual studies as well as using different effect models and detecting any publication bias using the harbord test. Results: Twenty-two studies were included in the final meta-analysis. Our results indicated that pregnant women with subclinical hypothyroidism had an increased risk of HDP (OR = 1.54(95% CI: 1.21-1.96) I²=67.1%), compared with euthyroidism. Subclinical hypothyroidism in pregnancy was not associated with hypertensive disorders of pregnancy at TSH diagnostic cut-off of less than 3.0 mIU/L (P = 0.077). Curiously, the risk of HDP increases when the TSH diagnostic cut-off value is higher or lower than 4 mIU/L. Although only 9 studies were above the threshold, the risk of developing HDP was still 1.69 times, which was highest in all subgroup analyses. This is consistent with the newly recommended diagnostic cut-off value of 4 mIU/L for TSH by the ATA. Our results consider that the risk of hypertensive disorder complicating pregnancy is increased regardless of the diagnosis of subclinical hypothyroidism at any stage of pregnancy. Unfortunately, there is insufficient evidence to support that patients can benefit from treatment with levothyroxine. Conclusion: The results of this meta-analysis indicate that subclinical hypothyroidism in pregnancy is associated with an increased risk of developing HDP, and this association exists regardless of the gestational period. However, the available evidence cannot support these patients receiving thyroxine intervention can benefit from it, so routine screening is only recommended for pregnant women with risk factors for hypothyroidism. Further research is needed to validate more scientific and rigorous clinical studies to clarify the relationship between subclinical hypothyroidism and HDP to improve patient prognosis. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, PROSPERO (CRD42021286405).

Global trends in research of immune cells associated with hypertensive disorders of pregnancy: A 20-year bibliometric analyses (from 2001 to 2021).

Background: A growing evidence suggests that immune cells play a significant role in the pathogenesis of hypertensive disorders of pregnancy (HDP).Over the past 20 years, several studies have been conducted on the role of immune cells in hypertensive disorders of pregnancy. This study used bibliometric analysis to assess research hotspots and future trends in studies on immune cells in hypertensive disorders of pregnancy. Methods: We extracted all relevant literature on immune cells and hypertensive disorders of pregnancy from the Web of Science core collection for the period of 2001 to 2021. We used VOS Viewer, CiteSpace, R-bibliometrix and Python for bibliometric analysis. Results: We identified 2,388 records published in 593 journals by 9,886 authors from 2,174 universities/institutions in 91 countries/regions. The number of publications tended to increase over time, with the highest number of publications in 2021, up to 205. The USA was the country with the most publications. UNIVERSITY OF MISSISSIPPI was the most influential institution. Lamarca B, Romero R, and Saito S were the most prolific authors. Finally, three research hotspot clusters were identified based on keywords, which reflected the role of immune cells in the development of hypertensive disorders of pregnancy, the current research status,and predicted hot spots for future research. Conclusions: Our study systematically analyzed the role of immune cells in the pathogenesis of hypertensive disorders of pregnancy in the last 20 years. Our results indicated that immune cells, such as T cells, natural killer (NK) cells,and macrophages, and the cytokines released such as TNF-α, IFN-γ in the maternal circulation and at the maternal-fetal interface would influence the development of hypertensive disorders of pregnancy and we need further investigate the role of individual immune cells and translational studies to provide new therapeutic perspectives to mitigate adverse perinatal outcomes due to hypertensive disorders of pregnancy. In conclusion, bibliometric studies provide a general overview of immune cells in the study of hypertensive disorders of pregnancy.

Cellular immune responses in the pathophysiology of preeclampsia.

Preeclampsia, defined as new-onset hypertension accompanied by proteinuria occurring at 20 weeks of gestation or later, is a leading cause of perinatal morbidity and mortality worldwide. The pathophysiology of this major multi-systemic syndrome includes defective deep placentation, oxidative stress, endothelial dysfunction, the presence of an anti-angiogenic state, and intravascular inflammation, among others. In this review, we provide a comprehensive overview of the cellular immune responses involved in the pathogenesis of preeclampsia. Specifically, we summarize the role of innate and adaptive immune cells in the maternal circulation, reproductive tissues, and at the maternal-fetal interface of women affected by this pregnancy complication. The major cellular subsets involved in the pathogenesis of preeclampsia are regulatory T cells, effector T cells, NK cells, monocytes, macrophages, and neutrophils. We also summarize the literature on those immune cells that have been less characterized in this clinical condition, such as γδ T cells, invariant natural killer T cells, dendritic cells, mast cells, and B cells. Moreover, we discuss in vivo studies utilizing a variety of animal models of preeclampsia to further support the role of immune cells in this disease. Finally, we highlight the existing gaps in knowledge of the immunobiology of preeclampsia that require further investigation. The goal of this review is to promote translational research leading to clinically relevant strategies that can improve adverse perinatal outcomes resulting from the obstetrical syndrome of preeclampsia.

Observation of changes in left atrial and left ventricular function in patients with hypertensive disorders of pregnancy based on myocardial strain.

BACKGROUND: To observe the changes of left atrial and left ventricular function in patients with hypertensive disorders of pregnancy (HDP) based on myocardial strain. METHODS: A total of 66 HDP patients admitted to our hospital were retrospectively analyzed, and 36 normal pregnant admitted during the same period women were selected as the control group. The maximum volume of the left atrium (LAVmax), minimum volume of the left atrium (LAVmin), left atrial active ejection fraction (LAAEF), mitral ratio of peak early to late diastolic filling velocity (E/A), and left ventricular active ejection fraction (LVEF) were measured by conventional echocardiography. The peak systolic strain rate (SRs) of each wall of the left atrium during early systole (SRe) and late diastole (SRa) was detected by speckle-tracking imaging (STI). The longitudinal (LS), radial (RS), and circumferential strain (CS) parameters of each wall of the left ventricle were also measured. The above parameters were compared between the two groups, and the correlation between mean SRa (mSRa) and LAAEF as well as left ventricular global longitudinal strain (GLS) and LVEF in HDP patients was analyzed. RESULTS: LAVmax, LAVmin, and LAAEF in the HDP group were higher than those in the control group, while the E/A ratio was lower than that in control group (all P<0.05). However, there was no significant difference in LVEF between the two groups (P>0.05). In the HDP group, the absolute values of SRs and SRe in each wall of the left atrium were lower than those in the control group, while the absolute values of SRa were higher than those in the control group. In addition, the absolute values of LS, CS, and RS values in each wall of left ventricle in the HDP group were lower than those in the control group (all P<0.05). Pearson correlation analysis showed that mSRa was negatively correlated with LAAEF (r=-0.895, P=0.000) and that left ventricular long-axis GLS was negatively correlated with LVEF (r=-0.646, P=0.000) in HDP patients. CONCLUSIONS: According to the STI results, HDP patients experience significant left atrial and left ventricular myocardial strain injury. Therefore, monitoring of cardiac function and early intervention should be strengthened in clinical practice.

Current Researches, Rationale, Plausibility, and Evidence Gaps on Metformin for the Management of Hypertensive Disorders of Pregnancy.

Hypertensive disorders of pregnancy (HDP) are a group of morbid pregnancy complications, with preeclampsia (PE) being the most common subclassification among them. PE affects 2%-8% of pregnancies globally and threatens maternal and fetal health seriously. However, the only effective treatment of PE to date is the timely termination of pregnancy, albeit with increased perinatal risks. Hence, more emerging therapies for PE management are in urgent need. Originally introduced as the first-line therapy for type 2 diabetes mellitus, metformin (MET) has now been found in clinical trials to significantly reduce the incidence of gestational hypertension and PE in pregnant women with PE-related risks, including but not limited to pregestational diabetes mellitus, gestational diabetes mellitus, polycystic ovary syndrome, or obesity. Additionally, existing clinical data have preliminarily ensured the safety of taking MET during human pregnancies. Relevant lab studies have indicated that the underlying mechanism includes angiogenesis promotion, endothelial protection, anti-inflammatory effects, and particularly protective effects on trophoblast cells against the risk factors, which are beneficial to placental development. Together with its global availability, easy administration, and low cost, MET is expected to be a promising option for the prevention and treatment of PE. Nevertheless, there are still some limitations in current studies, and the design of the relevant research scheme is supposed to be further improved in the future. Herein, we summarize the relevant clinical and experimental researches to discuss the rationale, safety, and feasibility of MET for the management of HDP. At the end of the article, gaps in current researches are proposed. Concretely, experimental MET concentration and PE models should be chosen cautiously. Besides, the clinical trial protocol should be further optimized to evaluate the reduction in the prevalence of PE as a primary endpoint. All of those evidence gaps may be of guiding significance to improve the design of relevant experiments and clinical trials in the future.

Hematocrit and plasma albumin levels difference may be a potential biomarker to discriminate preeclampsia and eclampsia in patients with hypertensive disorders of pregnancy.

BACKGROUND: We evaluated whether alterations of hemoglobin (HB), hematocrit (HCT), serum albumin level (ALB), and the difference of HCT and ALB can be used in the diagnosis of preeclampsia and eclampsia in patients with hypertensive disorders of pregnancy (HDP). METHODS: A total of 509 individuals were recruited and divided into 4 groups: Group 1, 170 healthy non-pregnant women; Group 2, 125 normal pregnant women; Group 3, 105 pregnant women diagnosed with gestational and chronic hypertension; Group 4, 109 pregnant women diagnosed as having preeclampsia and eclampsia. Data of HB, HCT, ALB, globulin (GLB) were collected at the time of a prenatal examination during the third trimester. RESULTS: Alterations in the HCT and the ALB levels in these groups were significantly different. Group 4 had a higher mean HCT-ALB value (P<0.01), but lower ALB and GLB values compared with the other three groups. We used Groups 2 and 3 as the respective reference to draw the receiver operating characteristic (ROC) curves of HCT-ALB in Group 4, and found that the threshold values of maximum index corresponding were 12.95 and 12.65 (sensitivity>57.0%, specificity>98.9%), respectively. CONCLUSIONS: The value of HCT-ALB>12.65 might be used as a potential biomarker for the auxiliary diagnosis of preeclampsia and eclampsia in HDP.