Maternal morbidity in postpartum severe preeclampsia by obstetric delivery volume.

BACKGROUND: Pre-eclampsia is a leading cause of maternal morbidity and mortality in the United States. Emerging data suggests that postpartum pre-eclampsia may be associated with a higher incidence of maternal morbidity compared to hypertensive disorders of pregnancy (HDP) diagnosed antenatally. Understanding postpartum maternal risk across facilities with a spectrum of obstetric services is critical with the rising rates of pre-eclampsia in all healthcare settings. OBJECTIVES: We investigated the relationship between facility delivery volume and rates of non-transfusion severe maternal morbidity (SMM) among patients readmitted postpartum for pre-eclampsia with severe features. STUDY DESIGN: This is a retrospective cohort study using the Nationwide Readmissions Database (2015-2019) of postpartum patients readmitted for pre-eclampsia with severe features. Our primary outcome was non-transfusion SMM during readmission, defined per U.S. Centers for Disease Control and Prevention criteria. We also evaluated SMM, cardiac SMM, and individual morbidities. The exposure variable was the number of annual deliveries at the readmitting facility. Restricted cubic splines with 4 knots were used to assess the functional form of the relationship between obstetric delivery volume and non-transfusion SMM; a linear relationship was identified as optimal. Logistic regression was used to estimate adjusted odds ratios (aOR) which controlled for maternal age, non-transfusion SMM at delivery, expanded obstetric comorbidity index, and HDP during delivery. RESULTS: The cohort included 29,472 patients readmitted with postpartum pre-eclampsia with severe features. The primary payer was 55% private and 42% governmental. Median age was 31.4 years. Most patients did not have prior HDP (65%) or chronic hypertension (86%) diagnosis antenatally. The median interval from delivery hospitalization to readmission was 3.9 days (25th percentile-75th percentile: 2.2-6.5). Non-transfusion SMM occurred in 7% of patients readmitted to facilities with >2,000 deliveries compared to 9% with 1-2,000 deliveries, and 52% without any delivery hospitalizations. The most common SMM was pulmonary edema and heart failure, observed in 4% of readmissions. We observed that for every increase in 1,000 deliveries, the odds of a non-transfusion SMM at readmission decreased by 3.5% (aOR: 0.965; 95% confidence interval: 0.94, 0.99) CONCLUSIONS: Non-transfusion SMM for postpartum readmissions with pre-eclampsia with severe features was inversely associated with readmitting hospital delivery volume. This information may guide risk-reducing initiatives for identifying strategies to optimize postpartum care at facilities with lower or no delivery volume.

Immune Cells and Infectious Diseases in Pre-eclampsia Susceptibility.

Pre-eclampsia is a severe pregnancy disorder affecting approximately 10% of pregnancies worldwide, characterized by hypertension and proteinuria after the 20th week of gestation. The condition poses significant risks to both maternal and fetal health, including cardiovascular complications and impaired fetal development. Recent trends indicate a rising incidence of pre-eclampsia, correlating with factors such as advanced maternal age and cardiovascular comorbidities. Emerging evidence also highlights a notable increase in the association between autoimmune and infectious diseases with pre-eclampsia. Autoimmune conditions, such as type 1 diabetes and systemic lupus erythematosus, and infections triggered by global health challenges and climate change, including Leptospirosis, Zika, Toxoplasmosis, and Chagas' disease, are now recognized as significant contributors to pre-eclampsia susceptibility by affecting placental formation and function. This review focuses on the immunological mechanisms underpinning pre-eclampsia, exploring how immune system dysregulation and infectious triggers exacerbate the condition. It also discusses the shared pathological mechanisms, including galectins, between autoimmune and infectious diseases with pre-eclampsia and their significant risk for adverse pregnancy outcomes. We emphasize the necessity for accurate diagnosis and vigilant monitoring of immune and infectious diseases during pregnancy to optimize management and reduce risks. By raising awareness about these evolving risks and their impact on pregnancy, we aim to enhance diagnostic practices and preventive strategies, ultimately improving outcomes for pregnant women, especially in regions affected by climatic changes and endemic diseases.

Three transposable elements exhibiting differential expression in pre-eclampsia overlap with enhancer regions.

Transposable elements (TEs) play a crucial role in placental development and dysfunction. Our study examined TE expression in pre-eclampsia (PE) using RNA-seq datasets. We identified differentially expressed TEs and explored the genomic location of the most significant TEs, investigating their possible regulatory roles. Notably, three TEs overlapped with putative enhancer regions, suggesting a potential regulatory impact on gene expression. These findings highlight the regulatory potential of TEs and their importance in placental development, supporting that TE dysregulation may contribute to PE pathogenesis.

A Systematic Review of Complications Following Pre-eclampsia.

INTRODUCTION: Most pregnancies are low-risk. However, sometimes women develop pre-eclampsia. The incidence varies based on different studies (Havers-Borgersen et al., 2023, 10.1136/jech-2023-220829).Pre-eclampsia is characterized by elevated blood pressure, protein in the urine, and excessive swelling and occurs after 20 weeks of pregnancy though in the case of severe symptoms, all may not be required for diagnosis (Bajpai et al., 2023). Many strategies exist to identify women with pre-eclampsia and to treat it. There are known immediate risks to both the mother and fetus. Some of these risks extend beyond the immediate postpartum period. Much less is known regarding the long-term risks. Therefore, the purpose of our study was to conduct a systematic review of the long-term complications related to pre-eclampsia. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) were used to guide this systematic review. PubMed, CINAHL, Medline, Scopus, PschINFO, and Google Scholar were used to identify relevant articles. We focused on articles published within the last 5 years. Search terms were pre-eclampsia and complications, pregnancy-induced hypertension and complications, long-term complications of pre-eclampsia, and long-term follow-up of pre-eclampsia. RESULTS: Two hundred and fifty-eight articles were identified; further analysis identified 91 that seemed relevant. After a thorough review, 19 articles were deemed relevant to identify complications women experience following pre-eclampsia. DISCUSSION: Cardiovascular disease is a major long-term risk. Early-onset pre-eclampsia contributes the greatest risk. Health promotion interventions that target women following a diagnosis of pre-eclampsia are needed. Inadequate knowledge exists to guide efforts to prevent long-term sequelae from pre-eclampsia.

Women who experience pre-eclampsia have significant health risks following the diagnosis. Some risks are immediate (elevated blood pressure) and some risks can take longer to develop (heart disease, diabetes, kidney disease). Because of these risks, it is critical to develop treatment strategies to prevent these risks if possible. There are also risks to the fetus/newborn and these may be amendable to intervention as well.

Nutraceuticals in Pregnancy: A Special Focus on Probiotics.

The placenta is crucial to fetal development and performs vital functions such as nutrient exchange, waste removal and hormone regulation. Abnormal placental development can lead to conditions such as fetal growth restriction, pre-eclampsia and stillbirth, affecting both immediate and long-term fetal health. Placental development is a highly complex process involving interactions between maternal and fetal components, imprinted genes, signaling pathways, mitochondria, fetal sexomes and environmental factors such as diet, supplementation and exercise. Probiotics have been shown to make a significant contribution to prenatal health, placental health and fetal development, with associations with reduced risk of preterm birth and pre-eclampsia, as well as improvements in maternal health through effects on gut microbiota, lipid metabolism, vaginal infections, gestational diabetes, allergic diseases and inflammation. This review summarizes key studies on the influence of dietary supplementation on placental development, with a focus on the role of probiotics in prenatal health and fetal development.

Benefits of simulation on multidisciplinary management of severe pre-eclampsia/severe eclampsia in 15 health districts in eastern Democratic Republic of Congo: A randomized educational trial.

OBJECTIVE: The purpose of the present study was to assess the benefits of simulation for advancing knowledge and assisting healthcare staff in optimization of procedures when managing severe pre-eclampsia/eclampsia (sPE/E). METHODS: A randomized educational trial was conducted with two groups: Group I received theoretical training, while group II received the same training along with simulation scenarios based on the management of sPE/E. The study involved 199 healthcare providers, including physicians, midwives, skilled birth attendants, and nurses. The study analyzed the percentage of correct answers on both the multiple-choice questions (MCQ) and the objective structured clinical examinations (OSCE) to evaluate theoretical knowledge and clinical skills objectively. RESULTS: Statistically significant differences were found immediately after training between groups I and II, whose mean percentages were 65.0% (±11.2) versus 71.0% (±9.8) (P < 0.001). A statistically significant reduction in the percentage of correct answers was found in both groups and demonstrated a discrepancy between immediate post-training test and post-training test at 3 months scores of 11.6% (±1.3) in group I versus 7.2% (±0.6) in group II. OSCE1 and OSCE2 scores were significantly higher in group II than in group I (P < 0.001). CONCLUSION: Simulation combined with theoretical training would appear to be an interesting method of training for advancing knowledge and improving skills of healthcare providers in their management of sPE/E. Our goal is for this method to be used to reduce real-life maternal mortality in the South Kivu region of the Democratic Republic of Congo.

Methylation alterations of imprinted genes in different placental diseases.

BACKGROUND: Imprinted genes play important functions in placentation and pregnancy; however, research on their roles in different placental diseases is limited. It is believed that epigenetic alterations, such as DNA methylation, of placental imprinting genes may contribute to the different pathological features of severe placental diseases, such as pre-eclampsia (PE) and placenta accreta spectrum disorders (PAS). RESULTS: In this study, we conducted a comparative analysis of the methylation and expression of placental imprinted genes between PE and PAS using bisulfite sequencing polymerase chain reaction (PCR) and quantitative PCR, respectively. Additionally, we assessed oxidative damage of placental DNA by determining 8-hydroxy-2'-deoxyguanosine levels and fetal growth by determining insulin-like growth factor 2 (IGF2) and cortisol levels in the umbilical cord blood using enzyme-linked immunosorbent assay. Our results indicated that methylation and expression of potassium voltage-gated channel subfamily Q member 1, GNAS complex locus, mesoderm specific transcript, and IGF2 were significantly altered in both PE and PAS placentas. Additionally, our results revealed that the maternal imprinted genes were significantly over-expressed in PE and significantly under-expressed in PAS compared with a normal pregnancy. Moreover, DNA oxidative damage was elevated and positively correlated with IGF2 DNA methylation in both PE and PAS placentas, and cortisol and IGF2 levels were significantly decreased in PE and PAS. CONCLUSIONS: This study suggested that DNA methylation and expression of imprinted genes are aberrant in both PE and PAS placentas and that PE and PAS have different methylation profiles, which may be linked to their unique pathogenesis.

[Which workup should be performed after a pregnancy complicated with vasculo-placental disorder?] / Quel bilan proposer après une grossesse compliquée de pathologie vasculo-placentaire ?

Vasculo-placental disorders include pregnancy complications resulting from placental dysfunction of vascular origin, i.e. pre-eclampsia, HELLP syndrome, intrauterine growth retardation (IUGR), placental abruption and stillbirth of vascular origin. Pre-eclampsia should be investigated for antiphospholipid syndrome (APS) in case of severe pre-eclampsia and premature delivery before 34 weeks of gestation. In addition to testing for APS, pathological report of the placenta can identify some anatomical predispositions to placental vascular malperfusion, as well as chronic placental inflammatory lesions and excess fibrin deposits. The latter two are associated with IUGR and recurrent stillbirth, reflecting a dysimmune process of maternal origin. The internal medicine and obstetrics consultation, organized two months after delivery, combines the postnatal visit with an assessment of the causes of vasculo-placental disorders, and enables to inform patients about the management of future pregnancies and their cardiovascular health.

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.

Perinatal outcomes in indian women with Antiphospholipid Antibody Syndrome (APS): Five year experience from a tertiary care centre.

Background: Antiphospholipid Syndrome (APS) is a systemic autoimmune thrombophilic condition characterized by obstetric manifestations, including pregnancy loss, preeclampsia and fetal growth restriction. Early diagnosis and management are key to improve maternal and neonatal outcomes. Objective: The aim of this study is to assess the perinatal outcomes in APS, the development of various adverse pregnancy outcomes (APO), and their association with specific antibody profiles. Material methods: This observational study was carried out on booked cases of singleton pregnancy and diagnosed cases of primary APS in our High-Risk Pregnancy (HRP) clinic from January 2018 to December 2022 after approval from institutional ethics committee. Forty-three confirmed cases of primary APS were enrolled and started on low-dose aspirin and low-molecular-weight heparin (LMWH) as per the patient's body weight after confirmation of fetal heart activity radiologically until 36 weeks of gestation as a standard of care. Results: Forty patients (93 %) had obstetric APS, and three patients (7 %) had thrombotic APS. During the course of the current pregnancy, adverse pregnancy outcomes (APO) developed in 12 (30 %) out of 40 cases of obstetric APS and in all 3 patients with thrombotic APS. Preeclampsia was seen in 11 (25.5 %), FGR in 12 (27.9 %), and preterm birth in 7 (16.2 %) cases. Patients with an antibody profile showing the presence of Anti-ß2 GP-I positivity and ACL positivity had fewer APOs (20 % and 29 %) in comparison to patients with a LA and triple positive antibody profile (55 % and 50 %). Conclusion: Treatment of pregnant women with APS causes significant improvement in the live birth rate. The late pregnancy complications like preeclampsia, FGR, and premature birth, occurring despite treatment still remains a challenge and emphasizes the need for stringent antepartum surveillance and timely delivery.

Let's not abandon programmed frozen embryo transfers yet: a countercurrent perspective.

The countercurrent opinion given in this paper is that the optimal management of frozen embryo transfers (FET) is not a one-size-fits-all matter, but rather one that should be decided after considering all the various parameters and options. This choice should notably encompass patients' individual characteristics - including variable risks of obstetric complications - and weigh out the respective advantages of each FET option in each case. While there may be real advantages for natural-cycle FET in many cases, these need to be balanced against both practical and clinical issues. Contrary to several prevailing, sometimes loudly expressed suggestions, there is not a one single effective approach when it comes to choosing a mode of scheduling FET.

Risk factors and clinical features of pre-eclampsia in Iranian and Afghan mothers: A comparative study.

OBJECTIVE: To assess variations in the presentation and clinical implications of pre-eclampsia between Iranian and Afghan mothers at a maternity center in Tehran. METHODS: We conducted a cross-sectional study of Iranian and Afghan mothers diagnosed with pre-eclampsia. Data were collected from March 2021 to February 2023 at a maternity center in Tehran, Iran. Demographic information, clinical characteristics, and laboratory findings were extracted from medical records. Statistical analyses were employed to compare differences between Iranian and Afghan mothers, including Mann-Whitney U, Pearson χ2 tests, and logistic regression models. RESULTS: We included 822 pregnant women with pre-eclampsia, predominantly Iranian (75.5%) and Afghan (24.5%). Regarding the multivariate logistic regression model, Iranian mothers were older, with a higher proportion over 35 years. Although Afghan mothers showed higher gravidity counts and greater gestational ages at delivery, they had lower rates of hypothyroidism. Iranian women were more often categorized as obese than Afghan women, and the difference was statistically significant. Serum levels of alkaline phosphatase were significantly greater in Afghan women. CONCLUSION: Pre-eclampsia poses significant maternal health risks, especially among Afghan refugees in Iran. Variances in age, gravidity, and hypothyroidism prevalence highlight the need for tailored healthcare strategies. Addressing cultural barriers and implementing targeted interventions can improve maternal and fetal outcomes in these populations.

Prior pre-eclampsia does not diminish the vascular protective effect of menopausal hormone therapy.

OBJECTIVE: Women with prior pre-eclampsia are at increased risk of cardiovascular disease (CVD). Menopausal hormone therapy (MHT) may affect this risk. We evaluated the impact of MHT use on cardiovascular risk between women with and without prior pre-eclampsia. STUDY DESIGN AND MAIN OUTCOME MEASURES: We assessed the occurrence of any CVD, myocardial infarction (MI) and stroke in MHT users (n = 9700) and non-users (n = 19,914) with prior pre-eclampsia, and likewise in MHT users (n = 27,764) and non-users (n = 58,248) without prior pre-eclampsia over the period 1994-2019. Follow-up started at MHT initiation (mean age 50.4 in pre-eclamptic women and 50.3 in non-pre-eclamptic women) and lasted for a mean of 13.3 years. RESULTS: The use of MHT in prior pre-eclamptic women was associated with significant risk reductions for any CVD (HR 0.85, 95 % CI 0.78-0.91), MI (HR 0.66, 95 % CI 0.55-0.78) and stroke events (HR 0.71, 95 % CI 0.63-0.81) in comparison with non-users with prior pre-eclampsia. The risk reductions for cardiovascular deaths were even more pronounced (HR 0.43, 95 % CI 0.31-0.59 for any CVD death; HR 0.49, 95 % CI 0.30-0.80 for MI death; HR 0.25, 95 % CI 0.10-0.64 for stroke death). However, none of these risk reductions differed from those seen in MHT users without prior pre-eclampsia. The risk of any CVD decreased already within five years of MHT use in women with prior pre-eclampsia but not in those without prior pre-eclampsia. CONCLUSIONS: The use of MHT is associated with reduced CVD risk in women with prior pre-eclampsia. This is important to clinicians considering the initiation of MHT for recently menopausal women with prior pre-eclampsia.

Prediction of Adverse Maternal Outcomes in Preeclampsia Using the FullPIERS (Preeclampsia Integrated Estimate of Risk) Model in a Tertiary Care Hospital of Eastern India.

INTRODUCTION: Preeclampsia, characterized by hypertensive disorders and systemic inflammatory response, remains a leading cause of maternal morbidity and mortality globally. Effective risk assessment tools are crucial for predicting adverse maternal outcomes. OBJECTIVE: This study evaluates the performance of the fullPIERS (Preeclampsia Integrated Estimate of Risk) model in predicting adverse maternal outcomes within 24 hours of admission for preeclampsia. METHODS: A cross-sectional study was conducted over one year, involving 100 preeclamptic patients admitted to Nil Ratan Sircar Medical College & Hospital (NRSMCH). Predictor variables were collected within 24 hours of admission and analyzed using the fullPIERS model. RESULTS: The fullPIERS model effectively stratified maternal risk. Adverse outcomes were significantly associated with systolic blood pressure (BP) ≥ 140 mmHg, diastolic BP ≥ 90 mmHg, oxygen saturation ≤ 95%, frontal headache, visual disturbances, chest pain/dyspnea, and abnormal random blood sugar, albumin, alanine aminotransferase, platelet count, and creatinine levels. A fullPIERS score ≥ 30 was strongly predictive of adverse maternal outcomes. CONCLUSION: The fullPIERS model is a valuable tool for predicting adverse maternal outcomes in preeclampsia, aiding in timely and effective clinical decision-making.

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 of the effects of PPIs during pregnancy on preeclampsia and related maternal, fetal and neonatal outcomes. DATA SOURCES: Five electronic databases (MEDLINE, Embase, CINAHL, Cochrane CENTRAL, and Global Medicus Index) were searched on 17 November 2023. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials involving pregnant women, using any class or dose of PPIs, were eligible. STUDY APPRAISAL AND SYNTHESIS METHODS: Meta-analysis was conducted for all outcomes of interest, with 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 (GRADE) assessment was completed to evaluate the certainty of the evidence. The study was registered on PROSPERO (CRD42023423673). RESULTS: Our search identified 3,879 records, which were screened by two authors independently. Nine reports (describing eight trials) met our eligibility criteria, however six trials were ultimately excluded from our analysis as women were only given PPIs immediately prior to Cesarean section for acid aspiration prevention. The two trials included in the meta-analysis evaluated the treatment of 177 women with diagnosed preeclampsia. For the primary outcomes, moderate-certainty evidence showed there is likely no effect of the use of PPIs on risk of HELLP syndrome (RR 1.21, 95% CI 0.37 - 3.99, I²â€¯= 0%) or perinatal mortality (RR 0.81, 95% CI 0.36 - 1.79, I²â€¯= 0%), while there were insufficient data to meta-analyse all other primary outcomes, including eclampsia and neonatal mortality. No trials investigated PPIs for preventing preeclampsia. CONCLUSIONS: Given the limited outcome data we are uncertain of the effect of PPIs in women with preeclampsia. Further trials are required to determine what (if any) effects PPIs might have for preeclampsia prevention or treatment.

AC092100.1 promotes angiogenesis in pre-eclampsia through YTHDC2/VEGFA signaling.

Aberrant long non-coding RNA (lncRNA) expression has been shown to be involved in the pathological process of pre-eclampsia (PE), yet only a small portion of lncRNAs has been characterized concerning the function and molecular mechanisms involved in PE. This study aimed to investigate the regulatory mechanism of the lncRNA AC092100.1 (AC092100.1) in angiogenesis in PE. In our study, bioinformatics analysis was performed to screen for differentially expressed lncRNAs between normal subjects and PE patients. The levels of AC092100.1 in placental tissues of patients with or without PE were validated using qRT-PCR. The effect of AC092100.1 overexpression on the proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) was investigated. The binding of AC092100.1 and YT521-B homology domain-containing 2 (YTHDC2) was predicted and verified. The effect of AC092100.1/YTHDC2 on the expression of vascular endothelial growth factor-A (VEGFA) in HUVECs was determined. Finally, a PE mice model was conducted. Fetal mouse growth, the abundance of mesenchymal morphology markers, including hypoxia-inducible factor 1-alpha (HIF-1α), soluble fms-like tyrosine kinase-1 (sFlt-1), soluble endoglin (sEng), Slug, and Vimentin, and endothelial markers, including placental growth factor (PLGF), CD31, and vascular endothelial (VE)-cadherin, in placental tissues were assessed. Here, we found that AC092100.1 was abnormally downregulated in placental tissues from PE patients. We established that AC092100.1 overexpression promoted HUVEC proliferation, migration, and tube formation in vitro. Mechanistically, AC092100.1 induced the accumulation of YTHDC2 and VEGFA through binding to YTHDC2 in HUVECs. Inhibition of YTHDC2 or VEGFA reversed AC092100.1-promoted tube formation. AC092100.1 overexpression contributed to alleviating fetal growth disorder, decreased levels of sEng, HIF-1α, sFlt-1, Slug, and Vimentin, and increased levels of VEGFA, PLGF, CD31, and VE-cadherin in PE mice. Our findings provided evidence supporting the role of the AC092100.1/YTHDC2/VEGFA axis in regulating angiogenesis, which demonstrated a therapeutic pathway for PE targeting angiogenesis.

Roles and action mechanisms of NRIP1 in pre-eclampsia.

BACKGROUND: Pre-eclampsia (PE) is characterized by the onset of hypertension and proteinuria during pregnancy. Here, we aimed to explore the functions of nuclear receptor-interacting protein 1 (NRIP1) in PE mice and human placental JEG-3 cells. We evaluated its effects on JEG-3 cell proliferation, apoptosis, invasion, and inflammatory response and regulation of Wnt/ß-catenin pathway. METHODS: NRIP1 levels in human serum and placental tissues, JEG-3 cells, and mouse models were assessed via quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting. JEG-3 cell growth, apoptosis, migration, and invasion were evaluated via 5-ethynyl-2'-deoxyuridine, flow cytometry, and transwell assays. Levels of the inflammatory factors, matrix metalloproteinase (MMP)-2, tumor necrosis factor (TNF)-α, and interleukin (IL)-6, were determined via enzyme-linked immunosorbent assay. Wnt/ß-catenin pathway was assessed via western blotting and qRT-PCR. Systolic blood pressure and proteinuria were measured using the non-invasive tail cuff method and Coomassie brilliant blue assay, respectively. TdT-mediated dUTP nick-end labeling assay was used to assess cell apoptosis in the placental tissues of PE mice. RESULTS: NRIP1 levels were upregulated in the serum and placental tissues of patients with PE. In vitro experiments revealed that NRIP1-small interfering RNA (siRNA) increased the cell viability, migration, and invasion and reduced the cell apoptosis compared to the control siRNA. Moreover, NRIP1-siRNA activated the Wnt/ß-catenin signaling pathway, as indicated by the increased Wnt3a, ß-catenin, p-glycogen synthase kinase-3ß, c-Myc, and cyclin D1 levels. Levels of the inflammatory factors, IL-6, TNF-α, and MMP-2, were decreased in the NRIP1-siRNA-treated group. Notably, NRIP1 downregulation improved the PE-like symptoms, inhibited the inflammatory responses, and reduced apoptosis in PE mice. CONCLUSION: This study revealed the crucial roles of NRIP1 in PE. Our findings revealed that NRIP1 downregulation relieved PE symptoms by inhibiting cell proliferation, migration, and invasion via the Wnt/ß-catenin pathway, thus providing a novel candidate for PE treatment.

Impact of isolated fetal congenital heart disease on pregnancy and perinatal outcomes.

OBJECTIVE: The aim of the present study was to evaluate the obstetric complications associated with isolated fetal congenital heart disease (CHD) by comparing pregnancies with and without this condition. METHODS: In this retrospective matched comparative study at Siriraj Hospital, Thailand, we included 233 postnatally confirmed fetal CHD cases and 466 unaffected fetuses. Controls were selected at a 2:1 ratio, ensuring that they matched the cases in terms of maternal age, parity, and history of preterm deliveries. RESULTS: Fetal CHD was significantly associated with an increased risk of spontaneous preterm labor (30% vs 9.7%; adjusted odds ratio [aOR] 2.42; 95% confidence interval [CI]: 1.35-4.36; P = 0.003), delivery before 34 gestational weeks (11.6% vs 0.6%; aOR 12.33; 95% CI: 3.32-45.78; P < 0.001), and pre-eclampsia (11.6% vs 2.8%; aOR 2.19; 95% CI: 1.01-4.76; P = 0.047). Newborns with CHD were significantly more likely to be small for gestational age (10.7% vs 5.2%; aOR 2.09; 95% CI: 1.11-3.94; P = 0.022). Intriguingly, a prenatal diagnosis of CHD was associated with a reduced risk of preterm delivery in affected pregnancies (P = 0.002). CONCLUSION: Pregnancies affected by isolated fetal CHD demonstrated a higher propensity for several adverse outcomes. These findings underscore the importance of prenatal CHD detection and tailored perinatal care to potentially improve both pregnancy outcomes and neonatal health.

Dysregulated Mitochondrial Calcium Causes Spiral Artery Remodeling Failure in Preeclampsia.

BACKGROUND: Calcium deficiency in women is strongly linked to an increased risk of developing preeclampsia. Mitochondrial calcium ([Ca2+]m) homeostasis is essential to regulate vascular smooth muscle cell (VSMC) function. However, the role of [Ca2+]m in preeclampsia development remains largely unknown. METHODS: To investigate this, human spiral arteries obtained from normotensive and preeclamptic women were collected for vascular function, RNA sequencing, and VSMC studies. N(ω)-nitro-L-arginine methyl ester-induced preeclampsia animal experiments were established to investigate the effects of intervening in [Ca2+]m to improve the outcome for preeclamptic mothers or their infants. RESULTS: Our initial findings revealed compromised vessel function in spiral arteries derived from patients with preeclampsia, as evidenced by diminished vasoconstriction and vasodilation responses to angiotensin II and sodium nitroprusside, respectively. Moreover, the spiral artery VSMCs from patients with preeclampsia exhibited phenotypic transformation and proliferation associated with the disrupted regulatory mechanisms of [Ca2+]m uptake. Subsequent in vitro experiments employing gain- and loss-of-function approaches demonstrated that the mitochondrial Na+/Ca2+ exchanger played a role in promoting phenotypic switching and impaired mitochondrial functions in VSMCs. Furthermore, mtNCLX (mitochondrial Na+/Ca2+ exchanger) inhibitor CGP37157 significantly improved VSMC phenotypic changes and restored mitochondrial function in both patients with preeclampsia-derived VSMCs and the preeclampsia rat model. CONCLUSIONS: This study provides comprehensive evidence supporting the disrupted regulatory mechanisms of [Ca2+]m uptake in VSMCs of spiral arteries of patients with preeclampsia and further elucidates its correlation with VSMC phenotypic switching and defective spiral artery remodeling. The findings suggest that targeting mtNCLX holds promise as a novel therapeutic approach for managing preeclampsia.

Causal association of sex hormone-binding globulin on gestational hypertension and pre-eclampsia: a two-sample Mendelian randomization study.

OBJECTIVES: Pre-eclampsia (PE) and gestational hypertension (GH) are two different categories of hypertensive disorders of pregnancy. Given earlier observational research, the relationship between sex hormone-binding globulin (SHBG) and a higher risk of GH/PE is still up for dispute. Hence, the present investigation aimed to examine the possible link between SHBG and the likelihood of GH/PE. METHODS: As a first stage, single nucleotide polymorphisms from summary-level genome-wide association studies were tightly screened using quality-control techniques. Afterward, we utilized a two-sample Mendelian randomization (MR) study to examine the causal impact of SHBG on the likelihood of GH/PE. There was no indication of a relationship between blood SHBG level (n = 214,989) and GH/PE (1864 cases and 461,069 controls) in the initial study. Consensus results were obtained from the replicated analysis, which utilized MR estimates based on serum SHBG level(n = 214,989) for GH (4255 cases and 114,735 controls). RESULTS: The findings did not indicate any proof of a cause-and-effect connection between SHBG and the likelihood of GH/PE (odds ratio [OR] = 0.99, 95% confidence interval [CI] = 0.999 - 1.00, p = .34). Replicate analysis also revealed similar patterns (OR = 0.92, 95%CI = 0.82-1.05, p = .21). The above findings were demonstrated to have a strong level of robustness. CONCLUSIONS: The findings of this research did not offer definitive proof to endorse the idea that SHBG has a direct causal impact on the likelihood of GH/PE, which goes against numerous widely accepted observational studies. To ascertain the potential processes behind the relationships seen in observational studies, more investigation is needed.