Human trophoblast invasion and migration are mediated by the YAP1-CCN1 pathway: defective signaling in trophoblasts during early-onset severe preeclampsia.

The transcription coactivator YAP1 mediates the major effects of the Hippo signaling pathway. The CCN family is a small group of glycoproteins known to be downstream effectors of YAP1 in diverse tissues. However, whether CCN family members mediate the effects of YAP1 in human trophoblasts is unknown. In this study, placental expression of both YAP1 and CCN1 was found to be impaired in pregnancies complicated by early-onset severe preeclampsia (sPE). CCN1 was expressed not only in cytotrophoblasts, trophoblast columns and mesenchymal cells, similar to active YAP1, but also in syncytiotrophoblasts of normal first-trimester placental villi; moreover, decidual staining of active YAP1 and CCN1 was found in both interstitial and endovascular extravillous trophoblasts. In cultured immortalized human trophoblastic HTR-8/SVneo cells, knockdown of YAP1 decreased CCN1 mRNA and protein expression and led to impaired cell invasion and migration. Also, CCN1 knockdown negatively affected HTR-8/SVneo cell invasion and migration but not viability. YAP1 knockdown was further found to impair HTR-8/SVneo cell viability via G0/G1 cell cycle arrest and apoptosis, while CCN1 knockdown had minimal effect on cell cycle arrest and no effect on apoptosis. Accordingly, treatment with recombinant CCN1 partially reversed the YAP1 knockdown-induced impairment in trophoblast invasion and migration but not in viability. Thus, CCN1 mediates the effects of YAP1 on human trophoblast invasion and migration but not apoptosis, and decreased placental expression of YAP1 and CCN1 in pregnancies complicated by early-onset sPE might contribute to the pathogenesis of this disease.

Enoxaparin sodium combined with magnesium sulfate in the treatment of severe preeclampsia.

Objective: To observe the treatment of severe preeclampsia in newborns with enoxaparin sodium combined with magnesium sulfate. Methods: A retrospective analysis was conducted on the clinical data of 80 patients with severe preeclampsia admitted to Hefei Second People's Hospital, China from January 2019 to December 2020. Treatment records showed that 40 cases received magnesium sulfate treatment (single group), and 40 cases received enoxaparin sodium combined with magnesium sulfate treatment (combination group). Levels of D-dimer, soluble fms-like tyrosine kinase 1 (sFlt-1), placental growth factor (PLGF), Apgar scores of newborns delivered before and after treatment were compared. Gestation weeks and incidence of adverse reactions were analyzed. Results: After treatment, levels of D-dimer, sfit-1 and adverse reactions in the combination group were significantly lower than those in the single group (P<0.05), and the level of PLGF, newborn Apgar score and length of gestation were significantly higher than those in the single group (P<0.05). Conclusion: Compared to magnesium sulfate alone, the combination of enoxaparin sodium and magnesium sulfate in the treatment of pregnant women with severe preeclampsia can more effectively regulate the cytokine level of patients, improve pregnancy outcome, and improve neonatal Apgar score. The incidence of adverse reactions is low, making it a safe and efficient treatment modality.

Effect of low-molecular-weight heparin calcium combined with magnesium sulfate and labetalol on coagulation, vascular endothelial function and pregnancy outcome in early-onset severe preeclampsia.

OBJECTIVE: This paper was aimed at unveiling the effect of low-molecular-weight heparin calcium (LMWH) combined with magnesium sulfate and labetalol on coagulation, vascular endothelial function, and pregnancy outcome in early-onset severe preeclampsia (EOSP). METHODS: Pregnant women with EOSP were divided into the control group and the study group, each with 62 cases. Patients in the control group were treated with labetalol and magnesium sulfate, and those in the study group were treated with LMWH in combination with the control grou Blood pressure (systolic blood pressure [SBP] and diastolic blood pressure [DBP]), 24-h urine protein, coagulation indices [D-dimer (D-D), plasma fibrinogen (Fg), prothrombin time (PT), activated partial thromboplastin time (APTT), and prothrombin time (TT)], endothelial function [endothelin (ET-1) and nitric oxide (NO)], oxidative stress indices [oxidized low-density lipoproteins (ox-LDL), lipid peroxidation (LPO), superoxide dismutase (SOD), and malondialdehyde (MDA)], pregnancy outcome, and adverse effects occurred in the two groups were compared. RESULTS: After treatment, lower SBP, DBP, and 24-h urine protein levels; lower Fg and D-D levels; higher PT, APPT, and TT levels; higher NO levels; lower ET-1 levels; lower ox-LDL, MDA, and LPO levels; higher SOD levels; and lower incidence of adverse pregnancy and adverse reactions were noted in the study group in contrast to the control group. CONCLUSION: EOSP patients given with LMWH combined with magnesium sulfate and labetalol can effectively reduce the patient's blood pressure and urinary protein level; improve coagulation function, oxidative stress, and vascular endothelial function indices; reduce the adverse pregnancy outcomes; and improve the safety of treatment.

Landscapes of gut bacterial and fecal metabolic signatures and their relationship in severe preeclampsia.

BACKGROUND: Preeclampsia is a pregnancy-specific disease leading to maternal and perinatal morbidity. Hypertension and inflammation are the main characteristics of preeclampsia. Many factors can lead to hypertension and inflammation, including gut microbiota which plays an important role in hypertension and inflammation in humans. However, alterations to the gut microbiome and fecal metabolome, and their relationships in severe preeclampsia are not well known. This study aims to identify biomarkers significantly associated with severe preeclampsia and provide a knowledge base for treatments regulating the gut microbiome. METHODS: In this study, fecal samples were collected from individuals with severe preeclampsia and healthy controls for shotgun metagenomic sequencing to evaluate changes in gut microbiota composition. Quantitative polymerase chain reaction analysis was used to validate the reliability of our shotgun metagenomic sequencing results. Additionally, untargeted metabolomics analysis was performed to measure fecal metabolome concentrations. RESULTS: We identified several Lactobacillaceae that were significantly enriched in the gut of healthy controls, including Limosilactobacillus fermentum, the key biomarker distinguishing severe preeclampsia from healthy controls. Limosilactobacillus fermentum was significantly associated with shifts in KEGG Orthology (KO) genes and KEGG pathways of the gut microbiome in severe preeclampsia, such as flagellar assembly. Untargeted fecal metabolome analysis found that severe preeclampsia had higher concentrations of Phenylpropanoate and Agmatine. Increased concentrations of Phenylpropanoate and Agmatine were associated with the abundance of Limosilactobacillus fermentum. Furthermore, all metabolites with higher abundances in healthy controls were enriched in the arginine and proline metabolism pathway. CONCLUSION: Our research indicates that changes in metabolites, possibly due to the gut microbe Limosilactobacillus fermentum, can contribute to the development of severe preeclampsia. This study provides insights into the interaction between gut microbiome and fecal metabolites and offers a basis for improving severe preeclampsia by modulating the gut microbiome.

Hepatic Rupture Associated With HELLP (Hemolysis, Elevated Liver Enzymes, and Low Platelets) Syndrome: A Report of Two Cases and Literature Review.

Hepatic rupture is a rare complication of severe preeclampsia. A high index of suspicion is required in the presence of abdominal pain accompanied by hemodynamic decompensation in a pregnant woman. Hepatic rupture constitutes a medical emergency that demands immediate intervention, often with the support of other medical disciplines, in a highly specialized hospital setting. Unruptured hepatic hematomas can be managed conservatively. Immediate delivery and surgical repair of the liver are necessary for maternal survival. Spontaneous liver rupture in pregnancy is often unrecognized, highly lethal, and not completely understood with few cases having been reported in the literature. Therefore, we present two cases of HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome with hepatic rupture, emphasizing their clinical presentation and therapeutic approaches.

Analysis of changes in high-mobility group box 1, receptor for advanced glycation endproducts, and T helper 17/regulatory T balance in severe preeclampsia with acute heart failure.

We measured the levels of High-Mobility Group Box 1 (HMGB1), Receptor for Advanced Glycation Endproducts (RAGE), T Helper 17 cells (Th17), Regulatory T cells (Treg), and related cytokines in the peripheral blood of patients with severe preeclampsia (SPE) complicated with acute heart failure (AHF) to explore the expression changes in these indicators. In total, 96 patients with SPE admitted to Gansu Provincial Maternity and Child-care Hospital between June 2020 and June 2022 were included in the study. The patients were divided into SPE+AHF (40 patients) and SPE (56 patients) groups based on whether they suffered from AHF. Additionally, 56 healthy pregnant women who either received prenatal examinations or were admitted to our hospital for delivery during the same period were selected as the healthy control group. An enzyme-linked immunosorbent assay was performed to detect the expression levels of HMGB1, RAGE, interleukin (IL)-17, IL-6, transforming growth factor ß (TGF-ß), IL-10, and NT-proBNP in plasma. Flow cytometry was employed to determine the percentages of Th17 and Treg cells. Compared to the healthy control group, the SPE+AHF and SPE groups had higher plasma levels of HMGB1 and RAGE expression, higher Th17 percentage and Th17/Treg ratio, and lower Treg percentage. Compared to the SPE group, the SPE+AHF group had higher plasma levels of HMGB1 and RAGE expression, higher Th17 percentage and Th17/Treg ratio, and lower Treg percentage (P < .05). In patients with SPE with AHF, plasma HMGB1 was positively correlated with RAGE, Th17, Th17/Treg, IL-17, and IL-6 and was negatively correlated with TGF-ß and IL-10 (P < .05). Our findings revealed that patients with SPE with AHF had elevated levels of HMGB1 and RAGE while exhibiting Th17/Treg immune imbalance, suggesting that the abnormal expression of these indicators may be involved in the pathogenesis of SPE with AHF.

Longitudinal changes of angiogenic factors as a potential predictive tool in women with suspected preeclampsia.

OBJECTIVES: To investigate whether longitudinal changes of angiogenic factors (AF) sFlt-1, PlGF, and the sFlt-1/PlGF ratio, measured following identification of symptoms of preeclampsia (PE), could provide complementary information to the isolated measurements used in current clinical practice. STUDY DESIGN: Retrospective observational study. Sixty women with suspected PE and two AF results measured before gestational week (GW) 34 were included. Daily variation (DV) of AF was calculated from delta values and days elapsed between measurements. Through ROC analysis, the predictive performance of DV for PE-related events was estimated. Kaplan-Meier survival curves resulting from applying cutoff values were assessed. RESULTS: The sFlt-1, PlGF, and sFlt-1/PlGF ratio baseline levels showed significant differences between women without PE and women who developed early-onset PE (P < 0.001). DV of sFlt-1 and sFlt-1/PlGF ratio increased according to the severity of PE, showing significant differences in both pairs of groups compared (p < 0.001), so they were selected as potential predictors. Higher AUC values resulting from ROC analysis were 0.78 for early-onset PE, 0.88 for early-onset severe PE, 0.79 for occurrence of adverse maternal outcomes, and 0.89 for delivery before 37 GW, with sensitivity and specificity values higher than 0.71 and 0.80, respectively. The Kaplan-Meier analysis yielded significantly different curves (log-rank < 0.05), with shorter time-to-delivery as DV increased. CONCLUSION: Our results support the existence of a correlation between a progressive PlGF and sFlt-1 imbalance and a more aggressive clinical course of PE, detectable from the finding of PE symptoms. Its monitoring could be a useful predictive tool in women with suspected PE.

Subphenotypes of severe early-onset pre-eclampsia at hospital admission. A Latin American single-center exploratory latent class analysis.

OBJECTIVES: To identify distinct subphenotypes of severe early-onset pre-eclampsia in Latin America and analyze biomarker and hemodynamic trends between subphenotypes after hospital admission. METHODS: A single-center prospective cohort study was conducted in Colombia. The latent class analysis identified subphenotypes using clinical variables, biomarkers, laboratory tests, and maternal hemodynamics. Class-defining variables were restricted to measurements at and 24 h after admission. Primary and secondary outcomes were severe maternal and perinatal complications. RESULTS: Among 49 patients, two subphenotypes were identified: Subphenotype 1 (34.7%) had a higher likelihood of an sFlt-1/PlGF ratio ≤ 38, maternal age > 35, and low probability of TPR > 1400, CO <8, and IUGR; Subphenotype 2 (65.3%) had a low likelihood of an sFlt-1/PlGF ratio < 38, maternal age > 35, and high probability of TPR > 1400, CO <8, and IUGR. At 24 h postadmission, 64.7% of subphenotype 1 patients changed to subphenotype 2, while 25% of subphenotype 2 patients were reclassified as subphenotype 1. Subphenotype 1 displayed significant changes in CO and TPR, while subphenotype 2 did not. Maternal complications were more prevalent in subphenotype 2, with an odds ratio of 5.3 (95% CI: 1.3-22.0; P = 0.02), but no significant differences in severe neonatal complications were observed. CONCLUSIONS: We identified two distinct subphenotypes in a Latin American cohort of patients with severe early-onset pre-eclampsia. Subphenotype 2, characterized by higher TPR, sFlt-1, and serum creatinine and lower CO and PlGF at admission, was associated with worse maternal outcomes and appeared less modifiable after in-hospital treatment.

Effect of Third Interstitial Fluid on Adverse Outcomes in Patients with Severe Pre-eclampsia and Twin Pregnancy: A 5-year Single-center Retrospective Study.

OBJECTIVE: This study aims to identify the effect of third interstitial fluid on adverse outcomes in twin pregnancies with severe pre-eclampsia, and explore the differences in bad ending between twins and singletons. METHODS: The present retrospective cohort study was conducted on patients with severe pre-eclampsia, who delivered in Tongji Hospital, Wuhan, China, between 2017 and 2022. The adverse outcomes in singleton and twin pregnancies with severe pre-eclampsia were initially investigated. Then, the diverse maternal and fetal consequences between singleton and twin pregnancies in patients with severe pre-eclampsia were compared after merging with the third interstitial fluid. RESULTS: A total of 709 patients were included for the present study. Among these patients, 68 patients had twin pregnancies, and 641 patients had singleton pregnancies. The rate of postpartum hemorrhage (2.81% vs. 13.24%, P<0.001), and admission rate to the Neonatal Intensive Care Unit (NICU) after birth (30.73% vs. 63.24%, P=0.011) were significantly higher in twin pregnancies. The neonatal weight of twins was statistically lower than singletons (1964.73±510.61 g vs. 2142.92±731.25 g, P=0.008). For the groups with the third interstitial fluid, the delivery week (P=0.001) and rate of admission to the NICU after birth were significantly advanced in twin pregnancy group, when compared to singleton pregnancy group (P=0.032), and the length of hospital stay was shorter (P=0.044). Furthermore, there was no statistically significant difference between the twin pregnancy group and the singletony pregnancy group without the third interstitial fluid. CONCLUSION: The maternal and fetal adverse outcomes of patients with severe pre-eclampsia increased in twin pregnancies, when compared to singleton pregnancies. Thus, when patients develop the third interstitial fluid, twin pregnancies would more likely lead to adverse fetal outcomes, when compared to singleton pregnancies, and there would be no significant difference in maternal adverse outcomes. More attention should be given to patients who merge with the third interstitial fluid.

Perinatal outcomes and their determinants among women with eclampsia and severe preeclampsia in selected tertiary hospitals, Eastern Ethiopia.

BACKGROUND: Neonatal complications and deaths are still increasing worldwide. Therefore, this study aimed to assess perinatal outcomes and their determinants among women with eclampsia and severe preeclampsia admitted to selected tertiary hospitals Eastern Ethiopia. METHODS: The prospective observational study was conducted among 245 foetal born to women with eclampsia and severe preeclampsia admitted to selected Hospitals. Data were collected from patients' charts and maternal interviews using questionnaires and telephone follow-ups from April 01 to September 30, 2022. Then, Cox regression were used to determine the predictors of perinatal clinical outcomes by SPSS (version 21.0®). Hazard ratios with a two-sided P-value < 0.05 were considered statistically significant. RESULT: Of 245 deliveries, perinatal mortality was 26.1 % and about 57.4 % of newborns developed neonatal complications. Fifth-minute Apgar score (AHR: 10.3; 95 % C.I: 3.8-28.1; P: 0.0001) was statistically a determinant to perinatal mortality whereas maternal parity (AHR: 1.7; 95 % CI: 1.0-2.86; P: 0.05), maternal diagnosis (AHR: 2.1; 95 % C.I:1.17-3.66; P: 0.012), maternal complications (AHR: 1.96; 95 % C.I: 1.13-3.41; P: 0.018) and fifth-minute Apgar score (AHR: 2.0; 95 % C.I: 1.29-3.19; P: 0.002) were found to be determinants for neonatal complications. CONCLUSION: Despite the inclusion of magnesium sulphate into the national drug list of Ethiopia to reduce maternal and perinatal morbidity and mortality, the perinatal condition remained a severe concern and worse among patients with eclampsia. Interventions to reduce the incidence of eclampsia, better antenatal care, early recognition, prompt treatment of severe preeclampsia, and enhanced neonatal care have to be initiated for patients.

Continuous non-invasive hemodynamic monitoring in early onset severe preeclampsia.

OBJECTIVES: Continuous hemodynamic monitoring offers the opportunity to individualize management in severe preeclampsia (PEC). We compared cardiac output (CO) and total peripheral resistance (TPR) measured by bioreactance (NICOM), Clearsite™ Fingercuff [CS), and 3D-echocardiography (3DE). STUDY DESIGN: This prospective observational study included 12 pregnant patients with early PEC. CO and TPR were measured simultaneously by NICOM, CS, and 3DE antepartum and 1-2 days postpartum. Using 3DE as the standard, CS and NICOM interchangeability, precision, accuracy, and correlation were assessed. RESULTS: Compared to 3DE-CO, CS-CO was highly correlated (R2 = 0.70, p = <0.0001) with low percentage error (PE 29%) which met criteria for interchangeablity. CS-TPR had strong correlation (R2 = 0.81, p = <0.0001) and low PE (29%). While CS tended to slightly overestimate CO (bias + 2.05 ±1.18 L/min, limit of agreement (LOA) -0.20 to 4.31) and underestimate TPR (bias -279 ±156 dyes/sec/cm5; LOA -580 to 18.4) these differences were unlikely to be clinically significant. Thus CS could be interchangeable with 3DE for CO and TPR. NICOM-CO had only moderate correlation with 3DE-CO (R2 = 0.29, p = 0.01) with high PE (52%) above threshold for interchangeability. NICOM-CO had low mean bias (-1.2 ±1.68 L/min) but wide 95% LOA (-4.41 to 2.14) suggesting adequate accuracy but low precision in relation to 3DE-CO. NICOM-TPR had poor correlation with 3DE-TPR (R2 = 0.32, p = 0.001) with high PE (67%), relatively low mean bias (238 ±256), and wide 95% LOA (-655 to 1131). NICOM did not meet the criteria for interchangeable with 3DE for CO and TPR. CONCLUSIONS: Clearsite Fingercuff, but not NICOM, has potential to be clinically useful for CO and TPR monitoring in severe preeclampsia.

Association of plasma Decorin levels and markers of glycocalyx disruption with adverse events in women with severe preeclampsia.

Identifying preeclamptic women with an increased risk of severe maternal complications can aid in timely interventions to optimize pregnancy outcomes. Newer biomarkers such as Decorin and markers of endo glycocalyx disruption were assessed in earlier studies for its role in predicting preeclampsia, but their role in identifying those with adverse maternal outcomes is limited. This study aimed to evaluate the association of these biomarkers with adverse maternal outcomes in women with severe pre-eclampsia. Markers of glycocalyx disruption may be further explored for their role along with clinical features and other biomarkers in identifying women at higher risk of maternal complications.

Labor Induction After Severe Preeclampsia With Maternal Posterior Reversible Encephalopathy Syndrome Complications Leading to Intrauterine Fetal Death: A Case Report.

Posterior reversible encephalopathy syndrome (PRES) is a clinical imaging syndrome characterized by vasogenic edema in the posterior cerebral circulation, with severe preeclampsia (PE) and eclampsia as major etiologies. Posterior reversible encephalopathy syndrome lesions are often reversible, but they can be potentially fatal in obstetric crises, causing serious complications such as cerebral hemorrhage, confusion, headache, visual symptoms, and stroke if not treated immediately. Neurological sequelae and even death may occur in a minority of these cases. In this paper, we report the case of a 26-year-old primigravida at 25 weeks of gestation who was irregular with obstetric visits. The patient presented with edema, nausea and vomiting, dizziness, blurry vision, falling down, and a maximum blood pressure of 190/85 mmHg. A brain MRI revealed PRES. Approximately 10 hours after admission, intrauterine fetal death occurred. After treatment, the patient was in stable condition and successfully induced for delivery.

Association of pre-pregnancy body mass index with early- and late-onset severe preeclampsia.

Objective: To determine whether maternal pre-pregnancy body mass index is associated with preeclampsia with severe features, categorized as early- or late-onset. Study design: This retrospective cohort study was conducted at the Department of Obstetrics and Gynecology, Rajavithi Hospital. The inclusion criteria were singleton pregnant women who gave birth at Rajavithi Hospital between January 1, 2015 and October 31, 2019. The study group was pregnant women diagnosed with preeclampsia with severe features while the control group was those without preeclampsia. Body mass index was classified based on The Regional Office for the Western Pacific Region of the World Health Organization criteria. The primary outcome was association of pre-pregnancy body mass index and risk of preeclampsia with severe features, classified by gestational age into early- (< 34 weeks) and late- (≥ 34 weeks) onset preeclampsia. Comparisons were made using the Student's t-test, Chi-square, or Fisher's exact tests, as appropriate. Logistic regression was used to assess associations. Results: There were 589 pregnant women in the control group and 519 women with preeclampsia in the study group. The study group was subdivided into early-onset (32.4 %, 168/519) and late-onset (67.6 %, 351/519) preeclampsia. Women who had preeclampsia with severe features had higher mean pre-pregnancy BMI than those without preeclampsia. Women with class I (63.6 %, 136/214) and II (81.0 %, 111/137) obesity (body mass index, 25.0-29.9 and ≥ 30.0 kg/m2, respectively) had significantly increased risk of preeclampsia with severe features (adjusted odds ratio 2.71, 95 % confidence interval 1.85-4.00 and adjusted odds ratio 3.84, 95 % confidence interval 2.22-6.64, respectively). In preeclampsia subgroup analysis, class I obesity was significantly associated with late-onset severe preeclampsia (adjusted odds ratio 2.02, 95 % confidence interval 1.40-2.93), while class II obesity was significantly associated with both early- and late-onset severe preeclampsia (adjusted odds ratio 1.69, 95 % confidence interval 1.01-2.84 and adjusted odds ratio 2.13, 95 % confidence interval 1.36-3.33, respectively). Conclusions: Class I and II obesity are significantly associated with preeclampsia with severe features. Class I obesity is significantly related to late-onset severe preeclampsia with, whereas class II obesity is associated with both early- and late-onset severe preeclampsia.

Matrix metalloproteinase-3 in preeclamptic and normotensive pregnancies complicated by foetal growth restriction.

The aim of the present study was to assess the interrelationships between the level of matrix metalloproteinase-3 in the blood serum of pregnant women and the occurrence of pregnancy complications in the form of foetal growth restriction, idiopathic or in the course of preeclampsia. Methods: A total of 245 patients were included in the study. 65 of them are normotensive patients with idiopathic foetal growth restriction (FGR group). 115 women were diagnosed with severe preeclampsia. In the group of women with preeclampsia, there were 51 patients with adequate for gestational age foetal growth and 64 patients with the foetal growth restriction in the course of severe preeclampsia. The control group consisted of 65 healthy patients with normal pregnancy course, with no cardiovascular disorders at the present and in the history, normal blood pressure and normal intrauterine foetal growth. Matrix metalloproteinase-3 (MMP-3) in maternal circulation were determined by ELISA method. Results: In our studies, we observed elevated levels of matrix metalloproteinase-3 in preeclamptic women with pregnancies complicated by FGR and significantly lower in the group of normotensive women with idiopathic FGR. The mean values of MMP-3 were 33.50 ± 65.74 ng/mL [Median (min-max) 19.19 (2.05-454.53)] in the Control group, 21.22 ± 23.28 ng/mL [Median (min-max) 16.39 (3.45-156.29)] in the FGR group, 35.96 ± 46.14 ng/mL [Median (min-max) 25.21 (4.16-253.05)] in the P group and 52.81 ± 61.61 ng/mL [Median (min-max) 32.83 (5.06-314.14)] in preeclamptic women with FGR (group PI) respectively.The assessment of MMP-3 in the serum of women with pregnancies complicated by intrauterine foetal growth restriction with normal values of blood pressure and in the group of preeclamptic patients in relation to healthy pregnant women with uncomplicated pregnancies and in relation to preeclamptic patients with normal intrauterine foetal growth is the novelty of this study. Such a strict definition of each research group seems to allow for the assessment of each pregnancy complication separately. Conclusion: It seems that higher levels of MMP-3 in preeclamptic women may suggest the need for observation towards the risk of lower birth weight of newborns. This necessitates further research and a better integration in the clinical practice.

Maternal and fetal outcomes in a retrospective cohort of obstetrical patients that used an insulin pump paired with a continuous glucose monitor.

OBJECTIVE: To assess maternal and neonatal outcomes in pregnant pregestational diabetic patients using a continuous subcutaneous insulin infusion (CSII) pump paired with a continuous glucose monitor (CGM). METHODS: This retrospective cohort study included 55 patients who delivered within one healthcare system from October 2019 to October 2022 with pregestational diabetes managed using CSII pumps paired with CGM. Maternal blood glucose (BG) data were analyzed for the two-week period preceding delivery. The percentage of time spent at a BG level of less than 140 mg/dL was recorded and compared between patients with and without obstetric and neonatal morbidities. RESULTS: Patients who delivered with severe preeclampsia (S. PreE) had a significantly lower mean percentage of time spent at BG < 140 mg/dL than those who did not (S. PreE 15/55, 63.1% ± 19.0 vs. 40/55, 73.6% ± 13.8; p = 0.03). Mothers who had a preterm birth (PTB) had a significantly lower mean percentage of time spent at BG < 140 mg/dL than those who delivered at term (PTB 35/55, 66.4% ± 16.4 vs 20/55, 78.3% ± 11.9; p = 0.006). The mean percentage of time spent at a BG < 140 mg/dL among mothers of neonates with respiratory distress syndrome (RDS) was significantly lower than those without RDS (RDS present 13/55, 59.7% ± 20.4 vs 42/55, 74.1% ± 12.7; p = 0.003). There was a significant correlation between a greater neonatal birth weight percentile and worse time spent at BG < 140 mg/dL (r = - 0.31; p = 0.02). No other significant differences were observed between the groups. CONCLUSION: Improved blood glucose levels in pregestational diabetic patients using a CSII pump and CGM is associated with reduced maternal and neonatal morbidity as well as lower birth weight percentile neonates. Future studies are needed to clarify how much time each day a patient needs to spend below a given blood sugar, how long this blood glucose should be maintained, and what specific blood glucose target should be selected.

Pregnancy outcomes and disease phenotype of hypertensive disorders of pregnancy in singleton pregnancies after in vitro fertilization: a retrospective analysis of 1130 cases.

BACKGROUND: Although in vitro fertilization (IVF) can increase the incidence of hypertensive disorders of pregnancy (HDP), the pregnancy outcomes and disease phenotype of HDP in singleton pregnancies conceived via IVF remain unclear. METHODS: This retrospective cohort study enrolled 1130 singleton pregnancies with HDP from 2016 to 2020. According to the mode of conception, they were allocated into IVF (n = 102) and natural conception (NC) groups (n = 1028). All IVF pregnancies were subdivided into frozen embryo transfer (FET) group (n = 42) and fresh embryo transfer (ET) group (n = 60). Demographic data, pregnancy outcomes and disease phenotypes of HDP among the groups were compared. The risk factors for severe preeclampsia (PE) and early-onset PE were analyzed. RESULTS: The incidences of early-onset PE (P<0.001), severe PE (P = 0.016), cesarean section (P<0.001) and preterm births (P = 0.003) in the IVF-HDP group were significantly higher than those in the NC-HDP group, and gestational age at diagnosis of HDP (P = 0.027) and gestational age at delivery (P = 0.004) were earlier and birthweight of the neonates (P = 0.033) were lower in the IVF group. In singleton pregnancies with HDP, IVF was associated with increased risks for both severe PE and early-onset PE (aOR 1.945, 95% CI 1.256, 3.014; and aOR 2.373, 95% CI 1.537, 3.663, respectively), as well as FET, family history of preeclampsia, intrahepatic cholestasis of pregnancy, gestational hypothyroidism and multiparity were associated with increased risks of severe PE and early-onset PE. CONCLUSIONS: In singleton pregnancies with HDP, IVF was associated with an increased incidence of the disease phenotype (severe or early-onset PE), as well as an increased incidence of pregnancy outcomes related to severe PE and early-onset PE.

Is There a Predictable Cost-Benefit Ratio in Preeclampsia?

Background Preeclampsia (PE) is one of the highest-risk pregnancies and a complicated condition that occurs in 2% to 8% of pregnancies and is associated with markers of a systemic inflammatory response (SIR). In this study, we aimed to determine the role of these markers in predicting PE. Methodology A total of 300 women with singleton pregnancies and cephalic presentation were included in the study. Normotensive pregnant women (n = 149) who met this criterion were included as the control group Pregnant women who met the inclusion criteria for a diagnosis of preeclampsia (n = 151) were included in the study group. Results The baseline characteristics of the study groups showed no significant difference. The hypertensive group was hospitalized significantly earlier than the control group (p < 0.001). We found significantly higher systolic and diastolic blood pressure values in the PE group than in the other group (p < 0.001). The mean neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and aspartate aminotransferase-to-platelet ratio index (APRI) values at hospitalization did not differ significantly between groups (p = 0.639, p = 0.709, and p = 0.066, respectively). In the receiver operating characteristic analysis curves compared with the control group and PE, none of the parameters could predict PE. Conclusions We found that NLR, PLR, and APRI have no clinical significance in assessing developmental risk and predicting PE.

Potential mechanism of transient receptor potential cation channel subfamily V member 1 combined with an ATP­sensitive potassium channel in severe preeclampsia.

Severe preeclampsia is one of the most serious obstetric diseases. However, the pathogenesis of the disease is not fully understood. In the present study, placental artery and blood serum was collected from patients with severe preeclampsia, as well as from normal pregnant women. The results of reverse transcription-quantitative (q)PCR, western blotting, and immunohistochemical staining revealed markedly decreased transient receptor potential cation channel subfamily V member 1 (TRPV1), ATP-sensitive potassium channel (KATP) subtype Kir6.1/SUR2B and endothelial nitric oxide synthase (eNOS) expression in severe preeclampsia tissue specimens compared with those in samples from normal pregnant women. The nitrate reduction method indicated lower NO levels in the tissue specimens and serum of patients with severe preeclampsia. Moreover, hematoxylin-eosin staining showed that the endothelial cell layer in the placental artery of patients with severe preeclampsia was notably damaged. To investigate the potential role of TRPV1-KATP channels in severe preeclampsia, HUVECs were used for in vitro experiments. The samples were divided into a control group, a TRPV1 agonist group (capsaicin) and a TRPV1 inhibitor group (capsazepine). qPCR and western blotting revealed that the relative gene and protein expression levels of TRPV1, Kir6.1, SUR2B and eNOS in the control group were significantly lower than those in the capsaicin group and considerably higher than those in the capsazepine group. Based on previous studies and the results of the present study, we hypothesized that impairment of the endothelial TRPV1-KATP channels results in decreased eNOS/NO pathway activity, which may be one of the mechanisms involved in severe preeclampsia. The increase in NO generation mediated by TRPV1-KATP may be a suitable target for the management of severe preeclampsia.