CircYTHDF1/miR-19b-3p/YTHDF1 axis contributes to pregnancy-induced hypertension development by enhancing vascular endothelial cell injury.

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-1ß, TNF-α, IL-6, TGF-ß1, 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.

Prevalence, underlying causes, and determinants of maternal near miss in Ethiopia: a systematic review and meta-analysis.

Background: Maternal near miss (MNM) is one of the newly adopted assessment parameters to gauge the quality of maternity care. In Ethiopia, several studies have been conducted to investigate the incidence, underlying causes, and determinants of MNM. However, the findings from those studies vary greatly and are largely inconsistent. Thus, this review aims to more robustly estimate the pooled prevalence, identify underlying causes, and single out determinants of MNM in Ethiopia. Methods: Studies were searched from international databases (PubMed/ Medline, Cochrane Library, and Embase databases) and other potential sites. All observational studies were included. Heterogeneity between studies was checked using Cochrane Q test statistics and I2 test statistics and small study effects were checked using Egger's statistical test at a 5% significance level. Outcome measures were overall and specific underlying causes (obstetrics hemorrhage, hypertensive disorder pregnancy, pregnancy-related infection) rates of MNMs per 10,000 live births. Result: The meta-analysis included 43 studies consisting of 77240 MNM cases. The pooled prevalence MNM per 1000 live births in Ethiopia was 54.33 (95% CI: 33.93 to 85.89). Between-study heterogeneity was high (I2 = 100%, P < 0.0001), with the highest rate observed in Amhara region (384.54 per 1000). The prevalence of obstetrics hemorrhage (14.56 per 1000) was higher than that of hypertensive disorder pregnancy (12.67 per 1000) and pregnancy-related infections (3.55 per 1000) were identified as underlying causes. Various factors, including socio demographic characteristics, previous medical and obstetrics history as well as access to and quality of care obtained, were associated with MNM. Conclusion: Almost six women encounter near miss among a hundred live births in Ethiopia. Obstetric hemorrhage and hypertensive disorder pregnancy were the most common underlying causes of MNM. Both individual and facility level determinants were found to be associated with MNM. Considering the magnitude and identified factors, tailored measures should be taken at every stage of the continuum of care. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023395259.

Scoping Review of Microbiota Dysbiosis and Risk of Preeclampsia.

Limited studies have investigated the role of the microbiota in hypertensive disorders of pregnancy (HDP), particularly preeclampsia, which often results in preterm birth. We evaluated 23 studies that explored the relationship between gut, vaginal, oral, or placental microbiotas and HDP. Scopus, ProQuest Health Research Premium Collection, ProQuest Nursing & Allied Health Database, EBSCO, and Ovid were searched for relevant literature. Majority (18) of studies focused on the gut microbiota, and far fewer examined the oral cavity (3), vagina (3), and placenta (1). One study examined the gut, oral, and vaginal microbiotas. The consensus highlights a potential role for microbiota dysbiosis in preeclampsia and HDP. Especially in the third trimester, preeclampsia is associated with gut dysbiosis-deficient in beneficial species of Akkermansia, Bifidobacterium, and Coprococcus but enriched with pathogenic Campylobacterota and Candidatus Saccharibacteria, with low community α-diversity. Similarly, the preeclamptic vaginal and oral microbiotas are enriched with bacterial vaginosis and periodontal disease-associated species, respectively. The trend is also observed in the placenta, which is colonized by gastrointestinal, respiratory tract, and periodontitis-related pathogens. Consequently, a chronic proinflammatory state that adversely impacts placentation is implicated. These observations however require more mechanistic studies to establish the timing of the preceding immune dysfunction and any causality.

A Cross-Sectional Study Comparing Placental Characteristics in Pregnancy-Induced Hypertension and Sickle Cell Anaemia.

BACKGROUND: Placental health plays a critical role in pregnancy outcomes as it serves as the interface between the mother and fetus. High-risk pregnancies, such as those complicated by pregnancy-induced hypertension (PIH) and sickle cell anaemia (SCA), are associated with significant alterations in placental morphology and histopathology, potentially leading to adverse maternal and fetal outcomes. While previous studies have explored placental changes associated with either PIH or SCA, nobody has comparatively analysed these conditions to understand their unique and overlapping effects on placental pathology. OBJECTIVE: This study aimed to compare and contrast the morphological and histopathological changes in the placenta associated with high-risk pregnancies like PIH and SCA. METHODS: A comparative analysis was conducted using data from studies at two different tertiary care centres. The study populations included 100 pregnant women diagnosed with PIH and 56 pregnant women with SCA, alongside a matched control group of 100 healthy pregnant women for the PIH group and 56 healthy pregnant women for the SCA group. Inclusion criteria were restricted to singleton pregnancies in women aged 18 to 35 years with gestational ages ranging from 28 to 40 weeks. Following delivery, placental specimens were collected, and various parameters such as weight, volume, surface area, number of cotyledons, and umbilical cord attachment were meticulously measured. Histopathological examinations were conducted to identify specific pathological features like infarcts, calcifications, syncytial knots, and fibrin deposition. Data analysis was performed using SPSS software version 25.0 (IBM Corp., Armonk, NY, USA), with a p-value of less than 0.05 considered statistically significant. RESULTS: The study revealed significant differences in placental parameters between the PIH and SCA groups compared to their respective controls. Placental weight, volume, and surface area were significantly reduced in both the PIH and SCA groups, with more pronounced reductions observed in PIH (p < 0.001). The umbilical cord attachment was predominantly marginal in the PIH group (75%), compared to a central attachment in the SCA group (70%), suggesting different patterns of placental development. Histopathological analysis demonstrated a higher incidence of infarcts (65% vs. 30%), calcifications (80% vs. 45%), syncytial knots (90% vs. 50%), and fibrin deposition (70% vs. 35%) in the PIH group compared to the SCA group, indicating more severe placental pathology in PIH. CONCLUSION: This study offered a comprehensive comparison of placental changes in pregnancies affected by PIH and SCA. It identified both structural abnormalities in terms of placental weight, volume, and surface area and distinctive pathological features like infarctions, calcifications, syncytial knot formation, and fibrin deposits in the placenta. When compared to control groups, these findings strongly suggest that placental dysfunction is a key contributor to the adverse outcomes associated with these high-risk pregnancies.

Effectiveness and safety of intravenous labetalol in severe pre-eclampsia and eclampsia at a teaching institution in Chhattisgarh.

Introduction: Severe hypertension in pregnancy deserves prompt recognition and urgent effective reduction in order to reduce the risk of complications such as eclampsia and HELLP syndrome and to achieve desirable neonatal outcomes. There is a need for effective and safe parenteral antihypertensive treatment. Subjects and Methods: We studied the effectiveness and safety of intravenous labetalol use in severe hypertension in pregnancy and post-partum period in a teaching hospital in Chhattisgarh in 101 women. IV labetalol was given as bolus doses till the blood pressures were controlled. Neonatal outcomes were recorded, and adverse effects such as hypotension, hypoglycemia, and neonatal asphyxia were documented. Results: Intravenous labetalol given as a single bolus of 20 mg was efficacious in controlling blood pressures in 93 out of 101 (93%) women, and the rest were controlled with 1 or 2 additional doses in 1-3 hours. No neonatal deaths happened beyond the 13 intrauterine fetal deaths at presentation. No women developed any episodes of hypotension, tachycardia of more than 100, or nausea or vomiting on labetalol. Conclusion: Intravenous labetalol, even as a single bolus dose, is highly efficacious and is free of any major adverse effects.

The role of arginase estimation to predict hypertensive disorder of pregnancy at an earlier stage.

Objectives: To determine the significance of serum arginase estimation as a predictor of pregnancy-induced hypertension and preeclampsia at an early stage. METHODS: The observational, cross-sectional study was conducted from October 15, 2021, to October 15, 2022, at the Department of Chemical Pathology, in collaboration with the Department of Obstetrics and Gynaecology, Pakistan Railway Hospital, Islamic International Medical College Trust, Rawalpindi, Pakistan, and comprised pregnant women with 20-25 weeks of gestation who were divided into three groups. Those having no complications were placed in control group A, those with pregnancy-induced hypertension in group B, and those with preeclampsia in group C. Serum arginase, uric acid, alanine transaminase, platelet count and spot urinary protein levels were measured for each subject. Data was analysed using SPSS 26. RESULTS: Of the 90 women, 30(33.3%) were in group A with mean age 27.27±2.90 years, 30(33.3%) were in group B with mean age 30.17±2.48 years, and 30(33.3%) were in group C with mean age 29.33±3.11 years. There were significant intergroup differences in the mean levels of serum arginase, serum uric acid, alanine transaminase, platelet count and spot urinary protein (p<0.05). CONCLUSIONS: A moderate to marked increase in serum arginase levels in pregnancy-induced hypertension and preeclampsia cases, combined with abnormal serum uric acid and alanine transaminase levels along with low platelet count suggested that serum arginase estimation could be used to predict hypertensive disorders of pregnancy at an early stage.

Risk factors for refractory respiratory distress syndrome among very-low-birth-weight infants.

BACKGROUND: The objective was to evaluate refractory respiratory distress syndrome (RDS) risk factors among very-low-birth-weight infants (VLBWIs). METHOD: The data of VLBWIs born between January 2013 and December 2020 registered in the Korean Neonatal Network (KNN) were analyzed. Infants who died within 5 postnatal days or who were not given surfactant were excluded. Infants were divided into a well-responding RDS group, which received surfactant replacement therapy (SRT) only once, and a refractory RDS group, which received SRT twice or more. The associations between perinatal characteristics and refractory RDS were investigated via multivariate logistic regression analysis. RESULTS: Multivariate logistic regression analysis revealed that low gestational age (adjusted odds ratio [aOR] = 1.26, 95% confidence interval (CI) [1.23, 1.26], male sex (aOR = 1.17, 95% CI [1.06, 1.29]), cesarean section (aOR = 1.59, 95% CI [1.38, 1.80]), maternal hypertensive disorder (aOR = 1.54, 95% CI[1.35, 1.75]), and low 5-minute Apgar scores (aOR = 1.24, 95% CI [1.12, 1.37]) were significantly associated with refractory RDS. Antenatal corticosteroid use (aOR = 0.81, 95% CI [0.73, 0.89]) and maternal chorioamnionitis (aOR = 0.79, 95% CI [0.71, 0.88]) were significantly inversely associated with refractory RDS. Compared with well-responding RDS, refractory RDS was significantly associated with increased major neonatal morbidity and mortality risk at 5 postnatal days. CONCLUSION: Maternal hypertensive disorder is a significant risk factor for refractory RDS. Refractory RDS was associated with unfavorable neonatal outcomes.

Association of Anti-Annexin A5 Antibody With Pregnancy Outcomes: A Cohort Study: Anti-annexin A5 antibody with pregnancy outcomes.

OBJECTIVE: This study aims to evaluate the correlation between anti-annexin A5 (aANXA5) antibody in the blood and pregnancy outcomes . METHODS: This study is a retrospective cohort study based on singleton pregnancies of the Third Affiliated Hospital of Wenzhou Medical University from May 2018 to December 2022. Baseline characteristics were collected from all participants. Logistic regression and interaction effect analyses were utilized to examine the risk impact of aANXA5 on pregnancy complications, adjusting for age, BMI, abortion, ANA, and aCL. Restricted cubic spline (RCS) and threshold effect analysis were applied to explore the relationship between aANXA5 levels and preterm birth (PTB), as well as pregnancy-induced hypertension (PIH). RESULTS: The study included 501 participants, with 51 (10.2%) testing positive for aANXA5 and 450 (89.8%) testing negative. The aANXA5 positive group exhibited higher rates of ANA and antibodies to thyroglobulin (TGAb), along with increased incidences of PTB and PIH. Positive aANXA5 status was independently linked to an elevated risk of PTB (OR: 2.53, 95% CI: 1.30-4.94) and PIH (OR: 4.23, 95% CI: 1.54-11.62). Subsequent subgroup analysis indicated no significant interaction between the groups (p > 0.05). Threshold analysis revealed that the OR for PTB was 1.20 (95% CI: 1.03-1.39) in participants with aANXA5 levels ≥ 32.77 ng/mL, and the OR for PIH was 1.62 (95% CI: 1.15-2.28) in those with aANXA5 levels ≥ 33.20 ng/mL. CONCLUSION: AANXA5 is independently associated with an increased risk of PTB and PIH. The identified optimal predictive cutoff values are 32.77 ng/mL for PTB and 33.20 ng/mL for PIH.

Management of Endocrinopathies During Pregnancy: A Systematic Review.

Uncertainty surrounds the efficacy and security of several medications in treating endocrinopathies, such as gestational diabetes mellitus (GDM) in individuals whose normal glucose levels cannot be maintained by diet and exercise alone. To improve pregnancy results for GDM individuals, the present review is conducted to measure the effectiveness of several antidiabetic medications for glucose management. Up until 2024, we looked through PubMed and Google Scholar. Patients with GDM were enrolled in randomized controlled studies that examined several medications. Using the Cochrane risk of bias method, we obtained the pertinent data and evaluated the bias probability. To determine the odds ratio and the surface of the cumulative ranking function of the maternal and neonatal consequences of various therapies in GDM individuals, we first performed pair-wise meta-assessments and subsequently used a systematic review. Macrosomia, higher gestational ages, infant hypoglycemia, and birth weight are the neonatal outcomes. Glycohemoglobin (HbA1c), and pregnancy-induced hypertension (PIH) are the maternal outcomes. This thorough analysis of 25 trial designs found that metformin had fewer cases of macrosomia, higher gestational ages, infant hypoglycemia, and decreased birth weight when compared to glyburide. Metformin was found to be the fastest way to control blood sugar levels in individuals with GDM, whereas glyburide was found to be the most successful medicine for the same purpose.

Comparative Study of Coagulation Profile and Haematological Parameters in Pregnancy-Induced Hypertension (PIH).

Background Pregnancy-induced hypertension (PIH) is a major cause of maternal and fetal morbidity and mortality. PIH, including gestational hypertension, pre-eclampsia, and eclampsia, often leads to significant alterations in coagulation profiles and haematological parameters, posing risks for thromboembolic and haemorrhagic complications. This study aimed to compare the coagulation and haematological parameters between women with PIH and normotensive pregnant women. Methods A cross-sectional observational study was conducted on 110 pregnant women, divided into two groups: 55 with PIH and 55 with normotensives. Coagulation markers such as prothrombin time (PT), activated partial thromboplastin time (aPTT), international normalised ratio (INR), and platelet count were measured. Bleeding and clotting times were also evaluated. Data were statistically analysed using student's t-test and chi-square tests, with p ≤ 0.05 considered significant. Results Women with PIH exhibited significantly lower platelet counts, PT, aPTT, and INR values compared to the normotensive group (p < 0.0001). Thrombocytopenia and prolonged bleeding time were more common in the PIH group, suggesting an increased risk of both bleeding and clotting complications. Proteinuria was observed in 32 women (58.18%) in the PIH group, reflecting the severity of the disease. Additionally, the PIH group had markedly elevated blood pressure levels. Conclusion PIH is associated with significant coagulation and haematological abnormalities, including thrombocytopenia and a hypercoagulable state, which increase the risk of thromboembolic and hemorrhagic events. Routine monitoring of coagulation profiles and haematological parameters in PIH patients is essential for timely interventions and improving maternal and fetal outcomes.

The optic nerve sheath in hypertensive disorders of pregnancy and perinatal outcomes: a cohort study.

BACKGROUND: Preeclampsia is implicated in 14% of maternal deaths worldwide, mostly due to complications such as intracranial hemorrhage and cerebral edema. Cerebral edema increases intracranial pressure, which can be predicted by ultrasonographic measurement of the optic nerve sheath diameter (ONSD). Greater diameters have been reported in women with preeclampsia and eclampsia; however, data are lacking on the possible association with maternal and neonatal adverse outcomes. This study aimed to determine whether there is an association between hypertensive disorders of pregnancy and the ONSD, and between this measurement and maternal and neonatal adverse outcomes. METHODS: This was a cohort study involving 183 women in the third trimester of pregnancy or within 24 h following childbirth, distributed as follows: control group (n = 30), gestational hypertension (n = 14), chronic hypertension (n = 12), preeclampsia without severe features (n = 12), preeclampsia with severe features (n = 62), superimposed preeclampsia (n = 23) and eclampsia (n = 30). The participants underwent ocular ultrasonography, and data on maternal and neonatal outcomes were collected from the medical records. To compare the groups, analysis of variance was used for the normally distributed numerical variables and the Kruskal-Wallis test was used for variables with non-normal distribution. Two-tailed p-values ≤ 0.05 were considered statistically significant. RESULTS: Overall comparison between the seven groups showed no statistically significant difference in the mean ONSD (p = 0.056). Nevertheless, diameters were significantly greater in the eclampsia group compared to the control group (p = 0.003). Greater diameters were associated with maternal admission to the intensive care unit (ICU) (p < 0.01) and maternal near miss (p = 0.01). There was no association between ONSD and admission to the neonatal ICU (p = 0.1), neonatal near miss (p = 0.34) or neonatal death (p = 0.26). CONCLUSIONS: No association was found between ONSD and the hypertensive disorders of pregnancy in the overall analysis; however, ONSD was greater in women with eclampsia compared to controls. Greater diameters were associated with maternal admission to the ICU and maternal near miss. These findings suggest a potential use for bedside ultrasound as an additional tool for stratifying risk in patients with hypertensive disorders of pregnancy.

Exploring the Spectrum of Electrolyte Imbalances in Preeclampsia: Mechanisms, Implications, and Clinical Insights.

Preeclampsia, a complex and perplexing disorder unique to pregnancy, is widely recognized as primarily originating from placental dysfunction and can only be resolved by the delivery of the fetus in severe cases. Preeclampsia is a prevalent medical issue during pregnancy and is associated with elevated rates of maternal and infant mortality and morbidity. The exact cause of preeclampsia remains uncertain, although multiple factors have been implicated in its development based on current knowledge. Preeclampsia is characterized by maternal endothelial dysfunction due to the presence of fetal-derived circulatory substances from the placenta. The condition is associated with various risk factors, including maternal comorbidities such as chronic renal disease, hypertension (HTN), and obesity. Additionally, a family history of preeclampsia, nulliparity, multiple gestations, previous instances of preeclampsia, or intrauterine fetal growth restriction (IUGR) are considered risk factors. Electrolytes, including sodium, potassium, and chloride, play a critical role in the function of vascular smooth muscles and may potentially contribute to the pathophysiology of hypertension. In this review, we have summarized the literature on electrolytes in preeclampsia by conducting an extensive systematic search of databases such as PubMed, Excerpta Medica database (EMBASE), and Medical Literature Analysis and Retrieval System Online (MEDLINE).

Retinal Microvascular Characteristics and Outcomes in Hypertensive Disorders of Pregnancy.

Background Hypertensive disorders of pregnancy (HDP) is a continuum of chronic hypertension, gestational hypertension, preeclampsia, and eclampsia in increasing severity, associated with a higher risk of complicated pregnancies and poor neonatal outcomes. This multisystem involvement can be assessed by fundoscopy, which serves as an indicator for generalized microvascular abnormalities. Our study aims to evaluate the correlation of hypertensive retinopathy with the severity of HDP and maternal and fetal outcomes. Materials and methods The study was conducted at a tertiary care hospital in Vijayapura from October 2021 to March 2022 among admitted cases of HDP. Detailed history, blood pressure (BP) measurement, obstetric examination, and fundoscopy were performed for all cases. Patients were followed up until the 10th postnatal day. The mode of delivery, birth weight, gestational age at birth, and any other neonatal outcomes were noted. Results We included 94 preeclampsia/eclampsia patients with a median age of 23 years, 51 (54.3%) being primigravida. Patients with chronic hypertension, gestational hypertension, and chronic hypertension superimposed by preeclampsia/eclampsia were excluded. The most common symptom in mothers was headache (23.4%), followed by blurring of vision (20.2%) and epigastric pain (5.3%) with a significant association (p < 0.05). Thirty-two cases (34%) had preterm deliveries with a positive association with the severity of retinopathy (p < 0.05). The magnitude of hypertensive retinopathy was 56.3% (53 cases), the severity of which significantly correlated to the severity of HDP (p < 0.05). We report 8.5% neonatal mortality and 22.3% small for gestational age (SGA) with a positive association with HDP severity (p < 0.05). There was no correlation between serum creatinine levels and the severity of retinopathy and fetal outcome. Conclusion The occurrence and severity of hypertensive retinopathy increase with increasing severity of HDP. Complaints, such as headache, blurred vision, and epigastric pain, are reported higher in cases with retinopathy. The severity of retinopathy may be used as an indicator of fetal morbidity; however, studies with large sample sizes and advanced tools are required to quantify the cause-effect relationship. The retinopathy associated with HDP resolves naturally with BP control postnatally.

The value of fetal left ventricular global longitudinal strain in predicting neonatal complications in pregnant women with hypertensive disorders.

BACKGROUND: Pregnancy-induced hypertension remains one of the important types of diseases that affect maternal and infant outcomes; prenatal and perinatal ultrasound examination is an important tool for evaluating fetal development. So, this study aimed to explore the clinical value of applying fetal heart quantification (fetal HQ) measuring left ventricular global longitudinal strain (LVGLS) and left ventricular ejection fraction (LVEF) in mid-to-late fetuses to predict neonatal complications in patients with gestational hypertension. METHODS: A retrospective summary of 146 pregnant women with gestational hypertension diagnosed from August 2020 to October 2023 into JinHua Maternal and Child Health Care Hospital was performed. Fetal HQ measured the fetal global spherical index (GSI), left and right ventricular spherical index (SI), left and right ventricular fractional shortening (FS), LVGLS and RVGLS, LVEF, and fractional area change (FAC) of the left and right ventricles. They were divided into complication group and non-complication group based on whether fetal complications occurred 28 days after birth. Multivariate logistic regression was used to screen risk factors to neonatal complications. RESULTS: The 146 neonates were divided into 39 of the complication group and 107 of the non-complication group. Compared with the latter group, pregnant women in the former group had a higher incidence of preeclampsia and eclampsia, increased mean systolic and diastolic blood pressure, significantly lower estimated fetal weight (EFW), left ventricular 24-segment SI, LVGLS, LVEF, and left ventricular FAC values (p < .05). Logistic regression showed higher of LVGLS (adjusted OR = 2.281, p < .001) was risk factors for neonatal complications, while higher LVEF (adjusted OR = 0.600, p < .001) and left ventricular FAC (adjusted OR = 0.784, p = .035) were protective factors. Spearman's correlation analysis showed a significant negative correlation between LVGLS and LVEF (r = -0.368, p < .001). Receiver operating curves (ROCs) showed the area under the curve (AUC) for predicting overall neonatal complications was 0.880 for LVGLS and 0.878 for LVEF (p < .001). CONCLUSIONS: Fetal HQ for fetal LVGLS and LVEF in mid-to-late pregnancy with gestational hypertension helps to assess the overall neonatal complications risk.

GDF-15 Alleviates Hypoxia-Reoxygenation-Induced Damage to Human Placental Vascular Endothelial Cells by Regulating SIRT1.

OBJECTIVE: Pregnancy-induced hypertension (PIH) is a common disease during pregnancy, which arises from maternal placental vascular endothelial cell dysfunction. Growth differentiation factor 15 (GDF-15) has a protective effect on the cardiovascular system. The purpose of this study is to explore the protective effect of GDF-15 against hypoxia-reoxygenation (H/R)-induced damage to human placental vascular endothelial cells (HPVECs) and the regulatory mechanism of SIRT1 in this effect. METHODS: Serum samples from healthy pregnant women and those with PIH were collected, and their GDF-15 and SIRT1 levels were examined. HPVECs were cultured in vitro and induced with H/R and GDF-15 at varying concentrations. The optimal concentration of GDF-15 in protecting HPVECs was determined by measuring cell viability via the CCK-8 assay. In H/R-induced HPVECs treated with GDF-15 and compound C (the AMPK inhibitor), expression levels of SIRT1, p-AMPK, and t-AMPK were detected. Cell apoptosis was examined by flow cytometry. RESULTS: Serum SIRT1 and GDF-15 were significantly higher in healthy pregnant women than in PIH patients. Suppressed viability and activated apoptosis in H/R-induced HPVECs were partially reversed by the treatment of GDF-15 at a concentration of 100 ng/mL. H/R induction significantly downregulated SIRT1 and p-AMPK in HPVECs, which were then upregulated by GDF-15. Moreover, the protective effect of GDF-15 on H/R-induced HPVECs was blocked by inhibiting the AMPK signaling pathway. CONCLUSION: GDF-15 protects against H/R-inhibited cell viability and H/R-stimulated apoptosis in HPVECs by activating the AMPK signaling pathway to upregulate SIRT1.

Comparison of isometric handgrip test among pregnant offspring of hypertensive parents and pregnant offspring of non-hypertensive parents.

Context: A family history of hypertension is one of the important risk factors for the development of pregnancy-induced hypertension (PIH). Offspring of hypertensive parents should be screened for PIH. The isometric handgrip (IHG) test is used to assess autonomic function among them. Autonomic function dysregulation can indicate their predisposition to develop PIH later in the course of pregnancy. Aim and Objectives: To compare the IHG among pregnant offspring of hypertensive parents (Group 1) and non-hypertensive parents (Group 2). Methods and Materials: This is a cross-sectional study done among 100 pregnant women in the second trimester (50 participants in each group). Blood pressure responses to sustained hand grip for 2 minutes of maximum voluntary contraction (MVC) were recorded, immediately at the end of the IHG test and after 5 minutes of the IHG test. Statistical Analysis: Independent t-test and Mann-Whitney U test were used to compare the responses in two groups. Results: There is no statistical difference in basal blood pressure and heart rate between the two groups. Group 1 exhibited a significant increase in systolic blood pressure (SBP) and diastolic blood pressure (DBP) compared to Group 2 immediately after 2 minutes of the IHG test. There is a significant increase in SBP after 5 minutes of the IHG in Group 2. Conclusions: Offspring of hypertensive parents have increased sympathetic reactivity and restoration of the blood pressure is significantly less compared to offspring of normotensive parents, which may predispose them for PIH. IHG can be applied as a convenient tool to screen the population who are at risk of PIH in places like primary health centres or field screenings where IHG is one possible option.

Metformin use and preeclampsia risk in women with diabetes: a two-country cohort analysis.

BACKGROUND: Metformin is a hypoglycaemic medication that has been proposed to treat or prevent preeclampsia. Combining national birth data from Scotland and Sweden, we investigated whether metformin used during pregnancy was associated with an altered risk of developing a hypertensive disorder of pregnancy. METHODS: We utilised data from two population-based cohorts: Scotland (2012-2018) and Sweden (2007-2019). Nulliparous women with gestational diabetes or type 2 diabetes who had birth outcome data linked with medications prescribed during pregnancy were included. The association between metformin prescription and hypertensive disorders of pregnancy was characterised using inverse probability weighted regression analysis, adjusting for variables that predict metformin use and potential confounders. Adverse neonatal outcomes were included as secondary outcomes. Results from both countries were then combined in a meta-analysis using a random effects model. RESULTS: The Scottish cohort included 3859 women with gestational diabetes or type 2 diabetes. Of these women, 30.8% (n = 1187) received at least one metformin prescription during pregnancy. For Sweden, 7771 women with gestational diabetes were included where 19.3% (1498) used metformin during pregnancy. Metformin prescription was not associated with an altered risk of any hypertensive disorder of pregnancy (Scotland adjusted relative risk (aRR) 0.88 [95% confidence interval (CI) 0.66-1.19]; Sweden aRR 1.08 [95% CI 0.86-1.37]) or preeclampsia (Scotland aRR 1.02 [95% CI 0.66-1.60]; Sweden aRR 1.00 [95% CI 0.72-1.39]). Combining adjusted results in a meta-analysis produced similar findings, with a pooled RR of 0.98 (95% CI 0.79-1.18) for any hypertensive disorder and RR 1.01 ([95% CI 0.73-1.28]) for preeclampsia. For neonatal outcomes, metformin was associated with a reduced risk of birthweight > 4500 g in Scotland (aRR 0.39 [95% CI 0.21-0.71]) but not in Sweden. There was no association between metformin and preterm birth or birthweight < 3rd or < 10th percentiles. Pooling results from both countries, metformin was not associated with adverse neonatal outcomes, including preterm birth (RR 1.00 [95% CI 0.89-1.13]), and birthweight < 10th percentile (RR 0.82 [95% CI 0.60-1.13]) or < 3rd percentile (RR 0.78 [95% CI 0.41-1.48]). CONCLUSIONS: In this two-country analysis, metformin use in pregnancy among women with diabetes was not associated with an altered risk of developing any hypertensive disorder of pregnancy. In the combined meta-analysis, metformin was not associated with an altered risk of adverse neonatal outcomes.

The effects of proton pump inhibitors during pregnancy on treatment of preeclampsia and related outcomes: a systematic review and meta-analysis.

OBJECTIVE: This systematic review evaluated the available evidence on the effects of proton pump inhibitors during pregnancy on preeclampsia and related maternal, fetal, and neonatal outcomes. DATA SOURCES: Five electronic databases (MEDLINE, Embase, CINAHL, Cochrane Central Register of Controlled Trials, and Global Medicus Index) were searched on November 17, 2023. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials of pregnant women who used any class or dose of proton pump inhibitor were eligible. METHODS: A meta-analysis was conducted for all outcomes of interest using random-effects models. Results were presented as risk ratios or mean difference. Quality assessment was performed using the Risk of Bias 2 tool, and Grading of Recommendations, Assessment, Development, and Evaluations assessment was completed to evaluate the certainty of the evidence. The study was registered in the International Prospective Register of Systematic Reviews under identifier CRD42023423673. RESULTS: Our search identified 3879 records that were screened independently by 2 authors. Nine reports (describing 8 trials) met our eligibility criteria, however, 6 trials were ultimately excluded from our analysis because women were only given proton pump inhibitors immediately before cesarean delivery for acid aspiration prevention. The 2 trials that were included in the meta-analysis evaluated the treatment of 177 women with diagnosed preeclampsia. For the primary outcomes, moderate-certainty evidence showed that the use of proton pump inhibitors likely has no effect on the risk for hemolysis, elevated liver enzymes, and low platelet count syndrome (risk ratio, 1.21; 95% confidence interval, 0.37-3.99; I²=0%) or perinatal mortality (risk ratio, 0.81; 95% confidence interval, 0.36-1.79; I²=0%), and there were insufficient data to conduct a meta-analysis on all other primary outcomes, including eclampsia and neonatal mortality. No trials investigated the use of proton pump inhibitors for the prevention of preeclampsia. CONCLUSION: Given the limited outcome data, we are uncertain about the effect of proton pump inhibitors on women with preeclampsia. Further trials are required to determine what (if any) effects proton pump inhibitors might have for preeclampsia prevention or treatment.

Correlation between Interleukin-10 Effects on Th1/Th2 Immune Balance and Pregnancy Induced Hypertension.

OBJECTIVE: Pregnancy induced hypertension (PIH) is a common disease in obstetrics. CD4+ T cells can be divided into Th1 and Th2 sub-populations. Imbalance between Th1 and Th2 directly affects body immune status and participates in PIH occurrence and progression. Whether IL-10 affects Th1/Th2 immune balance as a negative regulator of immune response in PIH remains unknown. The aim of the present study was to investigate the role of IL-10 in PIH. METHODS: A total of 52 PIH patients were recruited and divided into mild-moderate and severe PIH groups in parallel with 25 normal pregnant women as a control group. Real-time PCR was used to test mRNA levels of Th1 cytokines IL-2, tumor necrosis factor-α (TNF-α), and Th2 cytokines IL-4, IL-6, and IL-10. Enzyme linked immunosorbent assay (ELISA) tested serum levels of cytokines to analyze their correlation with disease progression. RESULTS: Our results showed PIH patients had significantly elevated IL-2 and TNF-α levels and decreased IL-4, IL-6, or IL-10 expressions compared with the control group (p<0.05). With disease progression, IL-4, IL-6, and IL-10 expressions were further decreased while IL-2 and TNF-α were increased (p<0.05). Moreover, IL-10 was negatively correlated with Th1 cytokines IL-2 and TNF-α while being positively correlated with Th2 cytokines IL-4 and IL-6. In addition, IL-10 was negatively correlated with PIH severity (p<0.05). CONCLUSION: IL-10 can affect Th1/Th2 immune balance and is associated with PIH severity, suggesting IL-10 might be a risk factor for PIH occurrence and progression.

The role of the cerebro-placental-uterine ratio in predicting composite adverse perinatal outcomes in patients with pregnancy-induced hypertension.

OBJECTIVES: To examine the role of the cerebro-placental-uterine ratio (CPUR) in predicting composite adverse perinatal outcomes (CAPO) in patients with pregnancy-induced hypertension (PIH). STUDY DESIGN: This prospective, case-control study was conducted at a tertiary hospital with 110 cases of PIH, including 70 patients with preeclampsia and 40 with gestational hypertension, and 110 healthy controls. The middle cerebral artery pulsatility index (MCA-PI), umbilical artery pulsatility index (UA-PI), and uterine artery pulsatility index (UtA-PI) were measured, and the cerebro-placental ratio (CPR=MCA-PI/UA-PI) and CPUR (CPR/UtA-PI) were calculated. MAIN OUTCOME MEASURE: The role of CPUR in predicting CAPO in preeclampsia and gestational hypertension. RESULTS: The CPR and CPUR values were lower in the PIH group compared to the control group (p < 0.001). CAPO had a negative correlation with CPR and CPUR (p < 0.001). Univariate regression analysis revealed that the likelihood of CAPO was increased four times by a low CPR value and six times by a low CPUR value. In the ROC analysis, the optimal cut-off value of CPR in predicting CAPO was 1.33 with 74 % sensitivity and 66 % specificity (area under the curve [AUC] = 0.778; p < 0.001) in PIH. For CPUR, the optimal cut-off value was 1.32, at which 82 % sensitivity and 79 % specificity in predicting CAPO (AUC=0.826; p < 0.001). CONCLUSION: CPUR was determined to be successful with high sensitivity in predicting adverse perinatal outcomes in the presence of PIH. In addition, CPUR was more effective in predicting CAPO in patients with preeclampsia compared to gestational hypertension. CPUR can be used to predict adverse outcomes in patients with PIH.