Hypertension in Pregnancy最新文献

Preeclampsia is a complex condition characterized by elevated blood pressure and organ damage involving kidneys or liver, resulting in significant morbidity and mortality for both the mother and the fetus. Increasing evidence suggests that oxidative stress, often caused by mitochondrial dysfunction within fetal trophoblast cells may play a major role in the development and progression of preeclampsia. Oxidative stress occurs as a result of an imbalance between the production of reactive oxygen species (ROS) and the capacity of antioxidant defenses, which can lead to placental cellular damage and endothelial cell dysfunction. Targeting oxidative stress appears to be a promising therapeutic approach that has the potential to improve both short- and long-term maternal and fetal outcomes, thus reducing the global burden of preeclampsia. The purpose of this review is to provide a comprehensive account of the mechanisms of oxidative stress in preeclampsia. Furthermore, it also examines potential interventions for reducing oxidative stress in preeclampsia, including natural antioxidant supplements, lifestyle modifications, mitochondrial targeting antioxidants, and pharmacological agents.A better understanding of the mechanism of action of proposed therapeutic strategies targeting oxidative stress is essential for the identification of companion biomarkers and personalized medicine approaches for the development of effective treatments of preeclampsia.

Background: Hypertensive disorders of pregnancy (HDPs), which include gestational hypertension (GH) and preeclampsia (PE), are the primary causes of maternal morbidity and mortality worldwide. Recent studies have found a correlation between metabolic dysfunction-associated steatotic liver disease (MASLD) and HDPs, but the causality of this association remains to be identified. Therefore, this study aims to evaluate the causal relationship between MASLD and HDPs through Mendelian randomization (MR) analysis.

Methods: The summary statistics from genome-wide association studies were employed to conduct a two-sample MR analysis. Five complementary MR methods, including inverse variance weighting (IVW), MR-Egger, weighted median, simple mode and weighted mode were performed to assess the causality of MASLD on GH and PE. Furthermore, we conducted various sensitivity analyses to ensure the stability and reliability of the results.

Results: Genetically predicted MASLD significantly increased the risk of GH (IVW: OR = 1.138, 95% CI: 1.062-1.220, p < 0.001), while there was little evidence of a causal relationship between MASLD and PE (IVW: OR = 0.980, 95% CI: 0.910-1.056, p = 0.594). The sensitivity analyses indicated no presence of heterogeneity and horizontal pleiotropy.

Conclusion: This MR study provided evidence supporting the causal effect of MASLD on GH. Our findings underscore the significance of providing more intensive prenatal care and early intervention for pregnant women with MASLD to prevent potential adverse obstetric outcomes.

Background: Preeclampsia (PE) is characterized as de novo hypertension (HTN) with end-organ damage, especially in the brain. PE is hypothesized to be caused by placental ischemia. PE affects ~5-8% of USA pregnancies and increases the risk for HTN and cerebrovascular diseases (CVD) later in life. We hypothesize that blood pressure (BP), cerebral oxidative stress, and cerebral inflammation will increase in postpartum (PP) placental ischemic dams.

Methods: Placental ischemia was induced in pregnant Sprague Dawley dams, utilizing reduced uterine perfusion pressure (RUPP) surgery. At 6 weeks PP (~3 human years), BP was measured via carotid catheterization, and cerebral oxidative stress and inflammation were assessed via ELISAs, biochemical assays, and Western blots.

Results: BP, cerebral pro-inflammatory cytokines (TNF-α and IL-6), and GFAP (a marker of astrocyte activity) were increased in PP RUPP dams. Cerebral hydrogen peroxide (H₂O₂) was also increased in PP RUPP dams, and had a strong correlation with PP RUPP BP, proinflammatory cytokines (TNF- α and IL-6), and GFAP astrocyte activation.

Conclusion: PP RUPP dams have increased BP, cerebral oxidative stress, and cerebral inflammation at 6 weeks postpartum. These changes in cerebral inflammation and oxidative stress may contribute to the pathology and development of HTN and CVDs in postpartum dams.

Objective: This was a pilot study to investigate the feasibility of developing a low-cost mobile technology-based intervention to encourage blood pressure (BP) monitoring and adoption of healthy lifestyle habits.

Methods: This was a prospective, controlled, randomized, non-blinding feasibility study that involved the use of electronic BP monitor and smartphone. Eligible participants in the intervention group were instructed to send the BP measurements to members of the LifeAPP team digitally from an application for smartphones linked to the BP device by Bluetooth and also via WhatsApp. The LifeAPP team sent feedback containing information as follows: a) safety of the BP levels; b) motivational messages aiming at maintaining self-monitoring; c) motivational messages aiming at the importance of developing healthy lifestyle habits. The primary outcome was feasibility: recruitment capacity, retention, and compliance with follow-up rates.

Results: Between 1 June 2020 and 24 January 2021, 48 participants were randomized to the intervention group, and 48 participants were randomized to the control group. The recruitment capacity of the participating centers proved to be adequate. Among the participants recruited for intervention group, 21 (43.7%) attended predefined visits at 3 months and only 12 (25%) attended predefined visits at 6 months. Similar loss to follow-up was observed in the control group.

Conclusion: Despite successful recruitment of a cohort of women following preterm preeclampsia, there was no sufficient retention of participants. Therefore, new strategies for long-term follow-up of women who developed preeclampsia are needed before a further study in this group of patients can be contemplated.

Preeclampsia is a complex, progressive multisystem hypertensive disorder during pregnancy that significantly contributes to increased maternal and perinatal morbidity and mortality. Two screening algorithms are in clinical use for detecting preeclampsia: first-trimester screening, which has been developed and validated for predicting early-onset preeclampsia but is less effective for late-onset disease; and the sFlt-1:PlGF biomarker ratio (soluble tyrosine kinase and placental growth factor) used in suspected cases of preeclampsia. This ratio has a high negative predictive value, allowing for the reliable exclusion of the disease. Both of these screening tests have not met expectations. This review attempts to summarize the current knowledge on the pathogenesis and prediction of preeclampsia and to draw attention to novel biomarkers with a focus on microRNAs and galectins. Although these molecules belong to two distinct biological classes, they functionally converge in regulating placental and immune pathways. Ample evidence supports their involvement in the molecular mechanisms underlying preeclampsia. Based on current knowledge, galectin-13, C19MC members, and miRNA-210 are associated with the trophoblast/placenta and conditions of placental ischemia or hypoxia. Their levels differ significantly in pregnant women at risk of preeclampsia as early as the late first and early second trimester, making them potential markers for predicting preeclampsia.

This study aimed to establish in vitro hemodilution and resupplementation assays for obstetric hemorrhage in pregnancy-induced hypertension (PIH) and to monitor the coagulation function dynamically using a coagulation and platelet function analyzer. Forty-seven singleton pregnant women were divided into normal (n = 24) and PIH (n = 23) groups. Peripheral blood samples were used to construct the assays, and the activated clotting time (ACT), clotting rate (CR), and platelet function index (PF) were measured. The results showed that the baseline ACT was higher in the PIH group (p < 0.01). Hemodilution assays showed decreased ACT and increased CR and PF, with ACT changes significantly lower in the PIH group (p < 0.05). CR changed most in both groups at lower dilution ratios (35% to 50%), while ACT changed most at a higher dilution ratio (75%). In the resupplementation assay, ACT exhibited the most significant response. The analyzer effectively detected differences between pregnant women with and without PIH. Thus, we need to pay more attention to the changes of ACT in the actual clinical application to assess the coagulation status of parturients.

Objective: This study was designed to investigate the effects of hypertensive disorders of pregnancy (HDP) on the complications in very low birth weight (VLBW) neonates.

Methods: We retrospectively included VLBW neonates (<37 weeks) who were delivered by HDP pregnant women with a body weight of < 1,500 g (HDP group) hospitalized in our hospital between January 2016 and July 2021. Gestational age matched VLBW neonates delivered by pregnant women with a normal blood pressure, with a proportion of 1:1 to the HDP group in number, served as normal control.

Results: Then we compared the peripartum data and major complications between HDP group and control. The body weight, prelabor rupture of membrane (PROM), maternal age, cesarean section rate, fetal distress, small for gestational age (SGA), mechanical ventilation, RDS, necrotizing enterocolitis (NEC) (≥2 stage), Apgar score at 1 min, and mortality in HDP group showed statistical differences compared with those of the control (all p < 0.05). To compare the major complications among HDP subgroups, we classified the VLBW neonates of the HDP group into three subgroups including gestational hypertension group (n = 72), pre-eclampsia (PE) group (n = 222), and eclampsia group (n = 14), which showed significant differences in the fetal distress, Apgar score at 1 min, SGA, ventilation, RDS and NEC (≥2 stage) among these subgroups (all p < 0.05). Multivariate regression analysis showed that eclampsia and PE were the independent risk factors for SGA and NEC, respectively.

Conclusion: HDP was associated with increased incidence of neonatal asphyxia, fatal distress, SGA, mechanical ventilation, RDS, NEC and mortality. Besides, eclampsia and PE were independent risk factors for SGA and NEC.

Objective: The biological role of circ_0004858 (circYTHDF1) in pregnancy-induced hypertension (PIH) and the underlying mechanisms were unknown, and which were explored in this study.

Methods: ELISA was employed to detect the level of inflammatory cytokines and biochemical parameters; flow cytometry was employed to detect cell apoptosis; western blot and qRT-PCR were employed to examine expression level.

Results: The level of IL-1β, TNF-α, IL-6, TGF-β1, ET-1, and Ang-II were significantly elevated in the peripheral blood of PIH patients. The co-culture of HUVEC and CD4+ T cells isolated from the peripheral blood of PIH patients significantly elevated the apoptosis and expression level of NRF2/HO-1 but reduced the protein level of ferroptosis-related markers (GPX4, FSP, and CoQ10B) in HUVEC. Also, the expression of circYTHDF1 and YTHDF1 were markedly up-regulated in HUVEC co-cultured with CD4+ T cells isolated from PIH patients, but miR-19b-3p expression was markedly down-regulated, and the similar results were observed in Ang-II-treated HUVEC. Based on the predicted binding sites, the luciferase reporter assay confirmed the interaction between miR-19b-3p and circYTHDF1 or YTHDF1. The results of qRT-PCR and western blot further demonstrated that circYTHDF1 competitively bound to miR-19b-3p to up-regulate YTHDF1 in HUVEC. Functionally, deleting circYTHDF1markedly reduced ferroptosis and apoptosis in Ang-II-treated HUVEC, but both which were reversed by miR-19b-3p inhibitor, suggesting the involvement of circYTHDF1/miR-19b-3p/YTHDF1 axis in vascular endothelial cell injury in PIH.

Conclusions: This study may provide a novel insight into the pathogenesis of PIH as well as a new treatment strategy.

Objectives: Magnesium sulfate (MgSO₄) is one of the most commonly used agents for the treatment and prophylaxis of eclampsia in patients with severe preeclampsia. However, there is no international consensus regarding the optimal gestational age for MgSO4 treatment. The aim of this study was to assess the effect of MgSO4 on uterine (UtA), umbilical, and fetal middle cerebral arteries (MCA) by calculating the SD ratio (S/D), resistance index (RI), and pulsatility index (PI) at different gestational weeks.

Methods: In total, 66 pregnant women as participants with severe preeclampsia were divided into two groups based on gestational age: Group 1 (n = 28, 26-30 weeks) and Group 2 (n = 38, 30-34 weeks). Color Doppler (Philip HD11) measurements were taken and compared before and after the MgSO4 loading dose.

Results: Within-group analysis revealed significant differences in RI-UtA, PI-UtA, and S/D in UtA before and after MgSO4 administration in Group 1. Furthermore, the RI-UA and RI-MCA decreased statistically significantly after MgSO4 treatment, whereas the pulsatility index and S/D did not change in either the umbilical or middle cerebral arteries. After MgSO4 treatment, all Doppler parameters in the uterine and umbilical arteries in Group 2 showed significant changes when compared to before MgSO4 administration.

Conclusion: MgSO4 can effectively improve umbilical and MCA blood flow at 30-34 gestational weeks but not at 26-30w. Meanwhile, using MgSO4 can improve uterine blood flow in severe preeclampsia, which may contribute to the management of reducing adverse events in pregnant women who have preeclampsia and fetal growth restriction.

Preeclampsia is a severe complication of pregnancy, affecting an estimated 4 million women annually. It is one of the leading causes of maternal and fetal mortality worldwide, and it has life-long consequences. The maternal multisystemic symptoms are driven by poor placentation, which causes syncytiotrophoblastic stress and the release of factors into the maternal bloodstream. Amongst them, the soluble fms-like tyrosine kinase-1 (sFLT-1) triggers extensive endothelial dysfunction by acting as a decoy receptor for the vascular endothelial growth factor (VEGF) and the placental growth factor (PGF). Current interventions aim to mitigate hypertension and seizures, but the only definite treatment remains induced delivery. Thus, there is a pressing need for novel therapies to remedy this situation. Notably, CBP-4888, a siRNA drug delivered subcutaneously to knock down sFLT1 expression in the placenta, has recently obtained Fast Track approval from the Food and Drug Administration (FDA) and is undergoing a phase 1 clinical trial. Such advance highlights a growing interest and significant potential in gene therapy to manage preeclampsia. This review summarizes the advances and prospects of gene therapy in treating placental dysfunction and illustrates crucial challenges and considerations for these emerging treatments.