Hypertensive Disorders Of Pregnancy Patients Research Articles

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.

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. 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. 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. NANOG downregulated the JAK/STAT3 pathway to promote trophoblast cell proliferation, migration and EMT through protein interaction with CDK1.

Development of phenotyping algorithms for hypertensive disorders of pregnancy (HDP) and their application in more than 22,000 pregnant women

Recently, many phenotyping algorithms for high-throughput cohort identification have been developed. Prospective genome cohort studies are critical resources for precision medicine, but there are many hurdles in the precise cohort identification. Consequently, it is important to develop phenotyping algorithms for cohort data collection. Hypertensive disorders of pregnancy (HDP) is a leading cause of maternal morbidity and mortality. In this study, we developed, applied, and validated rule-based phenotyping algorithms of HDP. Two phenotyping algorithms, algorithms 1 and 2, were developed according to American and Japanese guidelines, and applied into 22,452 pregnant women in the Birth and Three-Generation Cohort Study of the Tohoku Medical Megabank project. To precise cohort identification, we analyzed both structured data (e.g., laboratory and physiological tests) and unstructured clinical notes. The identified subtypes of HDP were validated against reference standards. Algorithms 1 and 2 identified 7.93% and 8.08% of the subjects as having HDP, respectively, along with their HDP subtypes. Our algorithms were high performing with high positive predictive values (0.96 and 0.90 for algorithms 1 and 2, respectively). Overcoming the hurdle of precise cohort identification from large-scale cohort data collection, we achieved both developed and implemented phenotyping algorithms, and precisely identified HDP patients and their subtypes from large-scale cohort data collection.

Angiogenic markers and maternal echocardiographic indices in women with hypertensive disorders of pregnancy.

The maternal cardiovascular system of women with hypertensive disorders of pregnancy (HDP) can be impaired, with higher rates of left ventricular (LV) remodeling and diastolic dysfunction compared to those with normotensive pregnancy. The primary objective of this prospective study was to correlate cardiac indices obtained by transthoracic echocardiography (TTE) and circulating angiogenic markers, such as soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF). In this study, 95 women with a pregnancy complicated by HDP and a group of 25 with an uncomplicated pregnancy at term underwent TTE and blood tests to measure sFlt-1 and PlGF during the peripartum period (before delivery or within a week of giving birth). Spearman's rank correlation was used to derive correlation coefficients between biomarkers and cardiac indices in the HDP and control populations. The HDP group included 61 (64.2%) pre-eclamptic patients and, among them, 42 (68.9%) delivered before 37 weeks' gestation. Twelve women with HDP (12.6%) underwent blood sampling and TTE after delivery, and, as they showed significantly lower levels of angiogenic markers, they were excluded from the analysis. There was a correlation between sFlt-1 and LV mass index (LVMI) (r = 0.246; P = 0.026) and early diastolic mitral inflow velocity (E) and early diastolic mitral annular velocity (e') ratio (r = 0.272; P = 0.014) in the HDP group (n = 83), while in the controls, sFlt-1 showed a correlation with relative wall thickness (r = 0.409; P = 0.043), lateral e' (r = -0.562; P = 0.004) and E/e' ratio (r = 0.417; P = 0.042). PlGF correlated with LVMI (r = -0.238; P = 0.031) in HDP patients and with lateral e' (r = 0.466; P = 0.022) in controls. sFlt-1/PlGF ratio correlated with lateral e' (r = -0.568; P = 0.004) and E/e' ratio (r = 0.428; P = 0.037) in controls and with LVMI (r = 0.252; P = 0.022) and E/e' ratio (r = 0.269; P = 0.014) in HDP. Although the current data are not able to infer causality, they confirm the intimate relationship between the maternal cardiovascular system and angiogenic markers that are used both to diagnose and indicate the severity of HDP. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

No evidence for a diminished ovarian reserve among patients with hypertensive disorders of pregnancy: a case control study

BackgroundExisting evidence suggests a relation between cardiovascular dysfunction and diminished ovarian reserve. While it is known that pre-existent cardiovascular dysfunction is also associated with the development of preeclampsia (PE) during pregnancy, we hypothesize that signs of diminished ovarian reserve may occur more frequently among women with a history of hypertensive disorders of pregnancy (HDP). The aim of our study was therefore to analyse if women with a history of HDP show signs of diminished ovarian reserve, represented by lower anti-Mullarian hormone (AMH) levels, compared to controls. For this retrospective observational case control study, patients included women with a history of HDP, whereas controls constituted of women with a history of an uncomplicated pregnancy. The study was conducted in a tertiary referral centre in which all women underwent a one-time cardiovascular and metabolic assessment. Ovarian reserve and markers of cardiovascular function were evaluated, adjusted for age and body mass index (BMI) using linear regression analyses.Results163 patients and 81 controls were included over a time span of 3 years. No signs of diminished ovarian reserve i.e. lower AMH level were observed in the patient group versus controls. A subgroup analysis even showed higher AMH levels in late onset HDP as compared to controls (2.8 vs. 2.0 µg/L, p = 0.025). As expected, cardiovascular function markers were significantly less favourable in the patient group compared to controls; higher levels of systolic blood pressure (BP) (5%), diastolic BP (4%), triglycerides (29%), glucose (4%) and insulin levels (81%) (all p < 0.05), whereas high density lipid (HDL) cholesterol was 12% lower (NS).ConclusionsDespite unfavourable cardiovascular risk profile, the present study does not substantiate the hypothesis that women with HDP show accelerated ovarian ageing as compared to healthy parous controls. Although HDP patients should be warned about their cardiovascular health, they shouldn’t be concerned about unfavourable ovarian reserve status.

Health-related needs of survivors of hypertensive disorders of pregnancy: implications for health communication interventions

ABSTRACT Background: Hypertensive disorders of pregnancy (HDP) are key contributors to maternal morbidity, mortality, and future risk of cardiovascular disease. This exploratory study aimed to unearth the health-related needs of women with a reported history of HDP by inquiring about preferences for care. Method: Deductive, qualitative analysis was conducted of HDP survivors’ retrospective ‘wishes’ about the care received. Results: In analyzing 244 open-ended, online survey responses, we identified a taxonomy of health-related needs arising across the trajectory of HDP: clinical information, needs requiring clinical knowledge, such as information about the etiology or prognosis of HDP; medical, needs associated with HDP intervention and management; logistical, needs regarding practical information, such as how to contact a provider or obtain the correct medical device; emotional, needs involving a desire for support or validation; and communication, needs for improved explanations and recognition of HDP. Conclusions: A taxonomy of diverse health-related needs may assist clinicians in approaching HDP patients more holistically. Additionally, opportunities exist for health communication research to inform standard approaches to HDP-related communication flowing from provider to patient.

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 from2020 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.

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 notchshowed 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.

Antihypertensive medication use during pregnancy in a real-world cohort of patients diagnosed with a hypertensive disorder of pregnancy.

Hypertensive disorders of pregnancy (HDP) are rising in prevalence and associated with adverse maternal and infant health outcomes. Current guidelines recommend labetalol, nifedipine, and methyldopa as acceptable first-line agents to treat HDP in outpatient settings. However, the current practice regarding antihypertensive medication usage and selection remain unclear. A retrospective, observational cohort study was conducted in 1,641 patients with a physician diagnosis of HDP who delivered at two academic medical centers in North Carolina from 2014 to 2017. Use of any antihypertensive medication, and the agent selected, at any encounter during pregnancy or on the delivery date was collected from the electronic health record. Proportions were compared across HDP diagnosis (eclampsia/severe preeclampsia, chronic hypertension with superimposed preeclampsia, preeclampsia, gestational hypertension) by Chi-square tests and multivariable logistic regression. Antihypertensive medications were used in 1,276 (77.8%) patients overall. Among treated patients, labetalol (74.9%) was the most frequently used medication followed by nifedipine (29.6%) and hydralazine (20.5%). Methyldopa was used infrequently (4.4%). HDP type was the strongest factor associated with use of an antihypertensive agent. Relative to gestational hypertension, antihypertensive use was significantly more likely [odds ratio (95% CI)] in patients with severe preeclampsia [5.94 (3.85-9.16)], chronic hypertension with superimposed preeclampsia [4.99 (3.46-7.19)], and preeclampsia [2.13 (1.61-2.82)]. In a real-world setting, antihypertensive medication use among HDP patients was common, labetalol, nifedipine, and hydralazine were the most commonly selected agents, and increasing HDP severity was associated with a higher likelihood of antihypertensive use. Future studies comparing medication effectiveness in pregnant patients with distinct HDP diagnoses are needed.

Risk factors associated with attendance at postpartum blood pressure follow-up visit in discharged patients with hypertensive disorders of pregnancy

BackgroundThis study aims to investigate the risk factors for not returning to postpartum blood pressure (BP) follow-up visit at different time points in postpartum discharged hypertensive disorders of pregnancy (HDP) patients. Likewise, females with HDP in China should have a BP evaluation continuously for at least 42 days postpartum and have BP, urine routine, and lipid and glucose screening for 3 months postpartum.MethodsThis study is a prospective cohort study of postpartum discharged HDP patients. Telephone follow-up was conducted at 6 weeks and 12 weeks postpartum, the maternal demographic characteristics, details of labor and delivery, laboratory test results of patients at admission, and adherence to BP follow-up visits postpartum were collected. While logistic regression analysis was used to analyze the factors associated with not returning to postpartum BP follow-up visit at 6 weeks and 12 weeks after delivery, the receiver operating characteristic (ROC) curve was drawn to evaluate the model’s predictive value for predicting not returning to postpartum BP visit at each follow-up time point.ResultsIn this study, 272 females met the inclusion criteria. 66 (24.26%) and 137 (50.37%) patients did not return for postpartum BP visit at 6 and 12 weeks after delivery. A multivariate logistic regression analysis identified education level of high school or below (OR = 3.71; 95% CI = 2.01–6.85; p = 0.000), maximum diastolic BP during pregnancy (OR = 0.97; 95% CI = 0.94–0.99; p = 0.0230)and delivery gestational age (OR = 1.12; 95% CI = 1.005–1.244; p = 0.040)as independent risk factors in predicting not returning to postpartum BP follow-up visit at 6 weeks postpartum, and education level of high school or below (OR = 3.20; 95% CI = 1.805–5.67; p = 0.000), maximum diastolic BP during pregnancy (OR = 0.95; 95% CI = 0.92–0.97; p = 0.000), delivery gestational age (OR = 1.13; 95% CI = 1.04–1.24; p = 0.006) and parity (OR = 1.63; 95% CI = 1.06–2.51; p = 0.026) as risk factors for not returning to postpartum BP follow-up visit at 12 weeks postpartum. The ROC curve analysis indicated that the logistic regression models had a significant predictive value for identify not returning to BP follow-up visit at 6 and 12 weeks postpartum with the area under the curve (AUC) 0.746 and 0.761, respectively.ConclusionAttendance at postpartum BP follow-up visit declined with time for postpartum HDP patients after discharge. Education at or below high school, maximum diastolic BP during pregnancy and gestational age at delivery were the common risk factors for not returning for BP follow-up visit at 6 and 12 weeks postpartum in postpartum HDP patients.

Physiologically Based Pharmacokinetic Modeling for Multiple Oral Administration Labetalol in Pregnant Women.

Labetalol has an irreplaceable role in treating Hypertensive disorders of pregnancy (HDP), a common disease during pregnancy with a prevalence of 5.2-8.2%. However, there were big differences in dosage regimens between various guidelines. A physiologically-based pharmacokinetics (PBPK) model was established and validated to evaluate the existing oral dosage regimens, and to compare the difference in plasma concentration between pregnant and non-pregnant women. First, non-pregnant woman models with specific plasma clearance or enzymatic metabolism (UGT1A1, UGT2B7, CYP2C19) were established and validated. For CYP2C19, slow, intermediate, and rapid metabolic phenotypes were considered. Then, a pregnant model with proper structure and parameters adjustment was established and validated against the multiple oral administration data. The predicted labetalol exposure captured the experimental data well. The following simulations with criteria lowering 15mmHg blood pressure (corresponding to around 108ng/ml plasma labetalol) found that the maximum daily dosage in the Chinese guideline may be insufficient for some severe HDP patients. Moreover, similar predicted steady-state trough plasma concentration was found between the maximum daily dosage in the American College of Obstetricians and Gynecologists (ACOG) guideline, 800mg Q8h and a regimen of 200mg Q6h. Simulations comparing non-pregnant and pregnant women found that the difference in labetalol exposure highly depended on the CYP2C19 metabolic phenotype. In summary, this work initially established a PBPK model for multiple oral administration of labetalol for pregnant women. This PBPK model may lead to personalized labetalol medication in the future.

Higher daytime systolic BP, prepregnancy BMI and an elevated sFlt-1/PlGF ratio predict the development of hypertension in normotensive pregnant women

BackgroundThe risk of hypertensive disorders of pregnancy (HDP) varies in women with gestational diabetes mellitus (GDM), depending on the degree of insulin resistance and is also influenced by obesity. The aim of this study was to evaluate clinical features, blood pressure (BP) profiles and inflammatory markers, to identify patients with an elevated risk of developing HDP.MethodsA total of 146 normotensive pregnant women were studied. We analysed the relationships of BP profiles detected by ambulatory blood pressure monitoring (ABPM) with serum biomarkers and angiogenic factors and their association with the development of HDP.ResultsFourteen (9.6%) women developed HDP, of which 11 had GDM and 8 had obesity. Women with HDP had higher values of 24-h and daytime systolic/diastolic BP (113/69 vs. 104/64; 115/72 vs. 106/66 mmHg, respectively; p < 0.05). Higher levels of leptin (10.97 ± 0.82 vs. 10.2 ± 1.11; p = 0.018) andmonocyte chemoattractant protein-1 (MCP-1) (5.24 ± 0.60 vs. 4.9 ± 0.55; p = 0.044) and a higher soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) ratio (4.37 ± 2.2 vs. 2.2 ± 1.43; p = 0.003) were also observed in the HDP patients. Multivariate analysis showed that a higher sFlt-1/PlGF ratio was associated with an increased risk of developing HDP [OR = 2.02; IC 95%: 1.35–3.05]. Furthermore, higher daytime systolic BP [OR = 1.27; IC 95% 1.00–1.26] and prepregnancy body mass index (BMI) [OR = 1.14; IC 95%: 1.01–1.30] significantly increased the risk of developing HDP.ConclusionsHigher daytime systolic BP values, prepregnancy BMI and the sFlt-1/PlGF ratio are useful for identifying normotensive pregnant women with an increased risk of developing HDP.

Home Quarantine: A Double-Edged Sword During COVID-19 Pandemic for Hypertensive Disorders of Pregnancy and the Related Complications.

ObjectCOVID-19 pandemic and worldwide quarantine seriously affected the physical and mental health of the general public. Our study aimed to investigate the effects of the COVID-19 quarantine on pregnancy outcomes among pregnant women with hypertensive disorders of pregnancy (HDP).MethodsThis single-center retrospective cohort study collected complete clinical data of HDP patients with a history of home quarantine in The First Affiliated Hospital of Chongqing Medical University (Chongqing, China) in 2020 as well as the patients without home quarantine in 2018 and 2019. Then, the maternal and neonatal outcomes of two subtypes of HDP, gestational hypertension (GH) and preeclampsia/eclampsia (PE/E), were analyzed over the three years.ResultsThe incidence of HDP increased from 0.84% in 2018 and 0.51% in 2019 to 2.30% in 2020. The data suggested that home quarantine was associated with higher gestational weight gain, obesity rates, blood pressure, and uric acid among the patients with HDP in 2020. Furthermore, HDP patients with a history of home quarantine may have worse neonatal outcomes, including lower newborn weight, shorter body length, lower Apgar score, and higher risk of fetal growth restriction.ConclusionOur results suggested that COVID-19 quarantine may be a risk factor for poor pregnancy outcomes in HDP patients. Lifestyle guidance and antenatal care may be necessary for HDP patients with home quarantine in an epidemic outbreak.

Results of a Prospective Registry of Patients with Hypertensive Disorders of Pregnancy in a Center of the City of Buenos Aires

Background: Hypertensive disorders of pregnancy (HDP) complicate 10% of pregnancies. They are the main cause of maternal mortality and require a multidisciplinary team to address them. Objectives: The aim of this study was to quantify the prevalence and define the characteristics and outcome of HDP in a center with a program focused on its management. Methods: This was a continuous and prospective registry from November 2019 to July 2021 that included all patients with HDP [chronic hypertension (CHT), gestational hypertension (GHT), early-onset preeclampsia (EPE), late preeclampsia (LPE), superimposed preeclampsia (SIPE) and eclampsia] who met the inclusion criteria. Patients without medical coverage that prevented longterm outpatient follow-up at the institution were excluded. Baseline characteristics and evolution, treatment and persistent HTafter puerperium were evaluated. The incidence of intrauterine growth retardation (IUGR), preterm delivery, maternal mortality and neonatal death within the first 28 days of life was analyzed. Results: Among a total of 5825 deliveries/caesarean sections, 152 patients with GHT (37.5%), EPE (19.7%), LPE (38.8%), SIPE (3.3%), and eclampsia (0.6%) who met the inclusion criteria were included in the study. Mean age was 36.4±5.6 years. Aspirin was administered to 38.1% of patients. The most commonly used antihypertensive drugs were labetalol (65.8%) and enalapril (44.1%) during pregnancy and puerperium, respectively. There was no maternal mortality, and neonatal mortality was 3.6%. Persistent HT was 20.0%. Conclusion: Late preeclampsia was the most frequent HDP in the population analyzed. More than half of the patients who developed HDP did not receive preventive treatment with aspirin, showing a deficit in the identification of the population at risk. One in 5 HDP patients remained with CHT after puerperium.

Resultados de un registro prospectivo de pacientes con desórdenes hipertensivos del embarazo en un centro de la Ciudad de Buenos Aires

Background: Hypertensive disorders of pregnancy (HDP) complicate 10% of pregnancies. They are the main cause of maternal mortality and require a multidisciplinary team to address them. Objectives: The aim of this study was to quantify the prevalence and define the characteristics and outcome of HDP in a center with a program focused on its management. Methods: This was a continuous and prospective registry from November 2019 to July 2021 that included all patients with HDP [chronic hypertension (CHT), gestational hypertension (GHT), early-onset preeclampsia (EPE), late preeclampsia (LPE), superimposed preeclampsia (SIPE) and eclampsia] who met the inclusion criteria. Patients without medical coverage that prevented long-term outpatient follow-up at the institution were excluded. Baseline charact ristics and evolution, treatment and persistent HT after puerperium were evaluated. The incidence of intrauterine growth retardation (IUGR), preterm delivery, maternal mortality and neonatal death within the first 28 days of life was analyzed. Results: Among a total f 5825 deliveries/caesarean sections, 152 patients with GHT (37.5%), EPE (19.7%), LPE (38.8%), SIPE (3.3%), and eclampsia (0.6%) who met the inclusion criteria were included in the study. Mean age was 36.4±5.6 years. Aspirin was administered to 38.1% of patients. The most commonly used antihypertensive drugs were labetalol (65.8%) and enalapril (44.1%) during pregnancy and puerperium, respectively. There was no maternal mortality, and neonatal mortality was 3.6%. Persistent HT was 20.0%. Conclusion: Late preeclampsia was the most frequent HDP in the population analyzed. More than half of the patients who developed HDP did not receive preventive treatment with aspirin, showing a deficit in the identification of the population at risk. One in 5 HDP patients remained with CHTN after puerperium.

Effects of Misoprostol on Induction of Labour in Patients with Hypertensive Disorders of Pregnancy: A Meta-Analysis.

Objective Hypertensive disorders of pregnancy (HDP) can cause serious prenatal and postnatal complications and is a threat to maternal and fetal health. To offer guidance for clinical decisions, we systematically reviewed the effects of misoprostol on induction of labour in HDP patients. Methods PubMed, Web of Science, Embase, CNKI, and Wanfang databases were searched for relevant literature from 2010 to 2020. Subsequently, a meta-analysis was performed to compare the effective rate of induction of labour and reducing postpartum hemorrhage (PPH) between the intervention group (n = 544, misoprostol) and the control group (n = 543, oxytocin). Results A total of 10 studies with 1087 patients were included. The 10 studies compared the effective rate of induction of labour between the two groups and confirmed that the effective rate in the intervention group was significantly higher than that in the control group (OR = 4.37; 95% CI: 2.73, 7.00). Seven studies compared PPH between the groups and showed that it was significantly reduced in the intervention group compared to the control group (SMD = −1.32; 95% CI: −2.05, −0.59; P < 0.0001). Conclusion Misoprostol has a high effective rate of induction of labour in HDP patients and is an effective uterotonic agent in reducing PPH. This meta-analysis provides clinicians with meaningful information to help them make evidence-based decisions.

SFlt-1/PlGF ratio in hypertensive disorders of pregnancy in patients affected by COVID-19.

ObjectivesTo analyze soluble Fms-like tyrosine Kinase 1 (sFlt-1) and Placental Growth Factor (PlGF) ratio concentrations in COVID-19 pregnant patients with and without Hypertensive Disorders of Pregnancy (HDP), compared with non COVID-19 pregnant patients with HDP and a control group.Study designWe recruited and obtained a complete follow-up of 19 COVID-19 pregnant patients with HDP and of 24 COVID-19 normotensive pregnant patients. Demographic, clinical and sFlt-1/PlGF ratio findings were compared with a group of 185 non COVID-19 pregnant patients with HDP and 41 non COVID normotensive patients. Findings were based on univariate analysis and on a multivariate adjusted model, and a case by case analysis of COVID-19 pregnant patients with an abnormal sFlt-1/PlGF ratio > 38 at recruitment.Main outcome measuressFlt-1/PlGF ratio.ResultsWe confirmed a significant higher prevalence of HDP in women affected by COVID-19 compared to control population. sFlt-1/PlGF ratio was found high in HDP patients, with and without of Sars-Cov2 infection. COVID-19 patients with worse evolution of the disease showed greater rates of obesity and other comorbidities. sFlt/PlGF ratio proved not to be helpful in the differential diagnosis of the severity of this infection.ConclusionsCOVID-19 pregnant patients showed a higher prevalence of HDP compared to non COVID-19 controls, as well as higher comorbidity rates. In spite of the possible common endothelial target and damage, between Sars-Cov-2 infection and HDP, the sFlt1/PlGF ratio did not correlate with the severity of this syndrome.

Atrial Natriuretic Peptide Inhibited ABCA1/G1-dependent Cholesterol Efflux Related to Low HDL-C in Hypertensive Pregnant Patients.

Objective: It has been reported that atrial natriuretic peptide (ANP) regulates lipid metabolism by stimulating adipocyte browning, lipolysis, and lipid oxidation, and by impacting the secretion of adipokines. In our previous study, we found that the plasma ANP concentration of hypertensive disorders of pregnancy (HDP) was significantly increased in comparison to that of normotensive pregnancy patients. Thus, this study’s objective was to investigate the lipid profile in patients with HDP and determine the effects of ANP on the cholesterol efflux in THP-1 macrophages.Methods: A total of 265 HDP patients and 178 normotensive women as the control group were recruited. Clinical demographic characteristics and laboratory profile data were collected. Plasma total triglycerides (TGs), total cholesterol (TC), low-density cholesterol (LDL-C), and high-density cholesterol (HDL-C) were compared between the two groups. THP-1 monocytes were incubated with different concentrations of ANP. ATP-binding cassette transporter A1 (ABCA1) and ATP-binding cassette transporter G1 (ABCG1) mRNA and protein were evaluated. ABCA1- and ABCG1-mediated cholesterol efflux to apolipoprotein A-Ⅰ (apoA-Ⅰ) and HDL, respectively, were measured by green fluorescent labeled NBD cholesterol. Natriuretic peptide receptor A (NPR-A) siRNA and specific agonists of the peroxisome proliferator–activated receptor-γ (PPAR-γ) and liver X receptor α (LXRα) were studied to investigate the mechanism involved.Results: Plasma TG, TC, LDL-C, and LDL-C/HDL-C were significantly increased, and HDL-C was significantly decreased in the HDP group in comparison to the control (all p < 0.001). ANP inhibited the expression of ABCA1 and ABCG1 at both the mRNA and protein levels in a dose-dependent manner. The functions of ABCA1- and ABCG1-mediated cholesterol efflux to apoA-I and HDL were significantly decreased. NPR-A siRNA further confirmed that ANP binding to its receptor inhibited ABCA1/G1 expression through the PPAR-γ/LXRα pathway.Conclusions: ABCA1/G1 was inhibited by the stimulation of ANP when combined with NPR-A through the PPAR-γ/LXRα pathway in THP-1 macrophages. The ABCA1/G1-mediated cholesterol efflux was also impaired by the stimulation of ANP. This may provide a new explanation for the decreased level of HDL-C in HDP patients.

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

To observe the changes of left atrial and left ventricular function in patients with hypertensive disorders of pregnancy (HDP) based on myocardial strain. 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. 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. 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.

Correlation between corin, N-terminal pro-atrial natriuretic peptide and neonatal adverse prognostic in hypertensive disorders of pregnancy.

Atrial natriuretic peptide (ANP) regulates water-salt balance and blood pressure by promoting renal sodium and water excretion. Our study was to investigate plasma N-terminal pro-atrial natriuretic peptide (NT-proANP) and corin in hypertensive disorders of pregnancy (HDP) patients. Furthermore, the relationship between corin/NT-proANP and neonatal adverse prognosis were evaluated. Seventy-seven HDP patients and forty-eight normotensive women as control group were recruited. Clinical characteristic and plasma were collected. Plasma NT-proANP and corin were determined by ELISA. Gestational age, neonatal weight and APGAR scores were recorded. Statistical analysis was conducted. NT-proANP and corin were significantly increased in HDP group compared with that of control (P<0.05). NT-proANP and corin were significantly elevated in HDP patients who suffered from premature delivery (P<0.05). Both NT-proANP and corin were negatively associated with delivery time, neonatal weight and APGAR scores in HDP group. Multiple regressions demonstrated that NT-proANP and corin were independent risk factor of delivery time, neonatal weight and APGAR scores. Plasma NT-proANP and corin were significantly increased in HDP. NT-proANP and corin were associated with neonatal adverse events in HDP patients. Thus, NT-proANP and corin may become new biomarkers for evaluating severity of pregnancy and neonatal adverse events in HDP patients.

Periodic Assessment of Antenatal and Post Natal Serum Endothelin-1 (ET-1) and Nitric Oxide (NO) Levels in Hypertensive Disorders of Pregnancy (HDP)

Hypertensive Disorders of Pregnancy (HDP) is an independent risk factor of cardiovascular (CVS) disease with endothelial dysfunction postulated to be the pathophysiology. Endothelin-1 (ET-1), a potent vasoconstrictor, has been identified as a pivotal mediator in HDP. Disturbances in nitric oxide (NO) bioavailability found in endothelial dysfunction may increase susceptibility to cardiovascular diseases such as hypertension. The study aims to determine serial ET-1 and NO levels in patients with HDP and its role in persistent endothelial dysfunction. Thirty-six pregnant women from the following categories (i) normal pregnant women (Control) (ii) chronic hypertension during pregnancy (CH) and (iii) pregnancy induced hypertension (PIH) participated in this study. Blood pressure indices measurements and sample collection were done at antepartum (32 weeks) and postpartum (8 weeks and 12 weeks). ET-1 and serum NO were measured using the Human ET-1 (Endothelin-1) ELISA Kit and Nitric Oxide (total) detection kit respectively. Results: Serum ET-1 was significantly higher in patients with CH (55.3 pg/ml) and PIH (35.6 pg/ml) compared to Control (11.8 pg/ml) during antenatal until 3 months postpartum (CH 38.3 pg/ml, PIH 29.5 pg/ml, Control 1.9 pg/ml). This was accompanied by significantly lower levels of serum NO in HDP patients. Persistently higher than normal levels of ET-1 and lower than normal levels of NO up to 3 months postpartum in patients with history of HDP indicate presence of persistent endothelial dysfunction despite BP normalisation in PIH patients. Long term NO/ET-1 imbalance may account for the increased CVS disease risk.