Early Onset Severe Preeclampsia Patients Research Articles

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.

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). 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. 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. 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.

Hierarchical lncRNA regulatory network in early-onset severe preeclampsia

BackgroundRecent studies have shown that several long non-coding RNAs (lncRNAs) in the placenta are associated with preeclampsia (PE). However, the extent to which lncRNAs may contribute to the pathological progression of PE is unclear.ResultsHere, we report a hierarchical regulatory network involved in early-onset severe PE (EOSPE). We have carried out transcriptome sequencing on the placentae from patients and normal subjects to identify the differentially expressed genes (DEGs), including some lncRNAs (DElncRNAs). We then constructed a high-quality hierarchical regulatory network of lncRNAs, transcription factors (TFs), and target DEGs, containing 1851 lncRNA-TF interactions and 6901 TF-promoter interactions. The lncRNA-to-target regulatory interactions were further validated by the triplex structures between the DElncRNAs and the promoters of the target DEGs. The DElncRNAs in the regulatory network were clustered into 3 clusters, one containing DElncRNAs correlated with the blood pressure, including FLNB-AS1 with targeting 27.89% (869/3116) DEGs in EOSPE. We further demonstrated that FLNB-AS1 could bind the transcription factor JUNB to regulate a series members of the HIF-1 signaling pathway in trophoblast cells.ConclusionsOur results suggest that the differential expression of lncRNAs may perturb the lncRNA-TF-DEG hierarchical regulatory network, leading to the dysregulation of many genes involved in EOSPE. Our study provides a new strategy and a valuable resource for studying the mechanism underlying gene dysregulation in EOSPE patients.

Relationship between parity and history of hypertension with MEOWS score in early onset severe preeclampsia patients

Introduction: Parity and a history of hypertension are some of the highest risk factors for severe preeclampsia, especially early onset. The severity of recurrent preeclampsia will increase compared to preeclampsia in the first pregnancy. Although there is a correlation between chronic hypertension and unfavorable pregnancy outcomes, several case-control studies have consistently shown that chronic hypertension is the most often acknowledged risk factor for adverse events affecting both the mother and the fetus. Women with the risk factors above can potentially fall into bad conditions, so close monitoring must be carried out. Modified Early Obstetric Warning System (MEOWS) is used for early detection, care, treatment, and referral of changes in obstetric patient parameters that are leading to worsening. Objective: Analyze the relationship between parity and history of hypertension with MEOWS scores in early-onset severe preeclampsia patients. Methods: A cross-sectional approach was used in this study by involving 63 patients. The population was early-onset severe preeclampsia patients treated at Dr. Soetomo Regional Public Hospital Surabaya Indonesia 2022; the sampling technique used was total sampling. This data was collected using secondary data from medical records and analyzed statistically using bivariate test, specifically the chi-square test using SPSS software. Results: The majority of patients were of reproductive age (73%), the gestational age was predominantly in the very preterm (28-<32 weeks) category (49.2%), the most obstetric status was multigravida (77.8 ), and most patients had no history of hypertension (66.7%). The average MEOWS score in early-onset PEB patients was 8.11. Parity vs MEOWS score (p>0.05), while the history of hypertension vs MEOWS score (p<0.05). Conclusion: Parity and MEOWS score did not have a significant relationship, while the history of hypertension had a significant relationship with MEOWS score.

The involvement of long noncoding RNA APOA1-AS in the pathogenesis of preeclampsia.

Long noncoding RNAs (lncRNAs) are involved in preeclampsia (PE), and apolipoprotein A-1 antisense RNA (APOA1-AS) and has been found to be associated with a number of diseases. Our study aims to understand the involvement of APOA1-AS in PE. Clinically, APOA1-AS expression in early-onset severe PE (EOSPE) patients and healthy controls was detected by real-time quantitative polymerase chain reaction. In vitro experiments were divided into control [coculturing trophoblasts with human uterine microvascular endothelial cells (UtMVECs)], TNF-α [coculturing trophoblasts with UtMVECs treated with tumor necrosis factor-α (TNF-α)], and TNF-α + control siRNA/APOA1-AS siRNA groups (UtMVECs transfected with control siRNA/APOA1-AS siRNA were cocultured with trophoblasts in the presence of TNF-α). The animals were divided into normal group, PE group (PE model was established by administrating nitro-L-arginine methyl ester (L-NAME) in rats), PE + control siRNA group (PE rats were treated with control siRNA), and PE + APOA1-AS siRNA group (PE rats were treated with APOA1-AS siRNA). Increased APOA1-AS was found in the placental tissues of EOSPE patients. APOA1-AS siRNA abolished the decreased integration of trophoblasts into UtMVEC networks induced by TNF-α. Furthermore, APOA1-AS siRNA improved pregnancy outcomes in PE rats with increased expression of vascular endothelial growth factor, placental growth factor, and fms-like tyrosine kinase receptor (Flt-1) but decreased expression of E-cadherin, intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Downregulation of APOA1-AS protected against TNF-α-induced inhibition of trophoblast integration into endothelial networks, thus exerting protective effects against PE rats.

Plasma Level of Umbilical Cord Hemeoxygenase-1 (HO-1) and Neonatal Outcome in Early Onset and Late Onset Severe Preeclampsia

Background: Many studies had discovered that early onset severe preeclampsia (EO-PE) has worst maternal and neonatal outcome compared to late-onset type (LO-PE), related to its placental involvement. Severe preeclampsia was defined as newly onset severe hypertension developed after 20 weeks gestation in previously normal blood pressure women, with coexistence of proteinuria, or maternal organ or uteroplacental dysfunction. Hemeoxygenase-1 (HO-1) is an enzyme with multiple effect which is protective to pregnancy.Materials and Methods: The total study subjects were 40 pregnant women consisted of 10 EO-PE, 10 normal early onset pregnancy (EO-NP), 10 LO-PE, and 10 normal late onset pregnancy (LO-NP). As much as 5 cc of plasma from umbilical cord was taken as soon as the baby was born, and the HO-1 level was examined by enzyme-linked immunosorbent assay (ELISA). The primary outcome were umbilical cord HO-1 level and neonatal composite morbidity (low Apgar score, low birthweight, length of stay >5 day, respiratory distress syndrome, jaundice and neonatal death).Results: The plasma level of HO-1 in EO-PE subjects were lower than EO-NP (0.96±0.37 ng/mL vs. 2.43±0.58 ng/mL, p<0.001). There were no significant differences in the level of HO-1 in LO-PE and LO-NP (2.18±1.07 ng/mL vs. 3.02±0.64 ng/mL, p=0.277). Plasma level of umbilical cord HO-1 of EO-PE patients was lower compared to LO-PE (0.96±0.37 ng/mL vs. 2.18±1.07 ng/mL, p=0.034). Neonatal outcome of EO-PE was worse than EO-NP (p=0.033), and LO-PE (p=0.003), while in LO-PE did not different with LO-NP (p=0.211).Conclusion: EO-PE is associated with lower plasma umbilical cord level of HO-1 and worse neonatal outcome compared to LO-PE. This indicating abnormal placental blood vessel development, placental ischemia in EO-PE, lead to reduced uteroplacental perfusion and significantly worse neonatal outcome compared to LO-PE.Keywords: severe preeclampsia, early onset preeclampsia, late onset preeclampsia, hemeoxygenase-1

Effect of predictive nursing on pregnancy outcome of early onset severe preeclampsia patients

Objective To explore the effect of predictive nursing on pregnancy outcome of early onset severe preeclampsia. Methods A total of 100 patients of early onset severe preeclampsia treated in the hospital were selected from January 2014 to April 2017.According to the different nursing intervention patterns, they were divided into the observation group and the control group, 50 cases of each group.Patients in the control group received conventional intervention. Patients in the observation group were given predictive nursing mode.Patients in both groups were given continuous intervention for 1 month.Pregnancy outcomes and perinatal outcomes were recorded and compared between the two groups.The occurrence of complications and patients' satisfaction were compared between the two groups. Results The incidence of postpartum hemorrhage and eclampsia in the observation group was significantly lower than that in the control group, and the difference was statistically significant(P<0.05). The incidence of intrauterine death, fetal distress and neonatal asphyxia in the observation group was significantly lower than that in the control group, and the difference was statistically significant(P<0.05). The incidence of complications in the observation group was significantly lower than that in the control group, and the difference was statistically significant(P<0.05). The satisfaction of the observation group was significantly higher than that of the control group, and the difference was statistically significant(P<0.05). There was no significant difference in diastolic blood pressure, systolic blood pressure and delivery gestational age between the two groups.The SAS score of patients in the observation group was significantly lower than that in the control group, and the difference was statistically significant(P<0.01). Conclusion Predictive nursing intervention for patients with early onset severe preeclampsia can significantly improve maternal and infant outcomes and anxiety, lessen the incidence of complications, and improve the satisfaction of patients.It is worthy of clinical application. Key words: Early onset severe preeclampsia; Predictive care; Pregnancy outcome; Satisfaction degree

Changes of platelet parameters in early severe preeclampsia

The pregnant women with SP or normal conditions were selected for the study, the platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW). and plateletcrit (PCT) were tested every four weeks, starting from 12(+1) to 16 gestational weeks, to compare the difference in platelet parameters between SP and normal pregnant women. PLT, MPV, and PDW of the early onset group exhibited statistically significant differences than the normal group from 20(+1) gestational weeks, and PCT of the early onset group exhibited statistically significant differences than the normal group from 28(+1) gestational weeks (p < 0.05); PLT, MPV, and PDW of the late onset group exhibited statistically significant differences than the normal group (p < 0.05), while PCT of the late onset group exhibited no statistically significant difference than the normal group from 12(+1) gestational weeks until childbirth (p > 0.05). The comparison between the early onset group and the late onset group revealed that there existed statistically significant differences in PLT, MPV, and PDW (p < 0.05), but PCT showed no statistically significant difference throughout the pregnancy period (p < 0.05). The changes of platelet parameters in early onset SP patients were earlier than the late onset group, and the difference was statistically significant (p < 0.05). Measuring the platelet parameters could better reveal early-stage SP, thus guiding more personalized clinical treatments to better protect maternal and child safety.

Differential Proteomic Analysis of Syncytiotrophoblast Extracellular Vesicles from Early-Onset Severe Preeclampsia, using 8-Plex iTRAQ Labeling Coupled with 2D Nano LC-MS/MS

Aims: Previous studies have revealed that the increased shedding of syncytiotrophoblast extracellular vesicles (STBM) may lead to preeclampsia (PE). We aimed to identify the proteins carried by STBM and their potential pathological roles in early-onset severe PE. Methods: In this study, we performed a differential proteomic analysis of STBM from early-onset severe PE patients, using iTRAQ isobaric tags and 2D nano LC-MS/MS. STBM were generated by the in vitro explant culture method, and then verified by electron microscopy and western blot analysis. Results: A total of 18 533 unique peptides and 3 317 proteins were identified, 3 292 proteins were quantified. We identified 194 differentially expressed proteins in STBM from early-onset severe PE patients, 122 proteins were up-regulated and 72 proteins were down-regulated. Further bioinformatics analysis revealed that mitochondrion, transmembrane transport and transmembrane transporter activity were the most abundant categories in gene ontology (GO) annotation. Glycolysis/ gluconeogenesis, citrate cycle, fatty acid elongation, steroid hormone biosynthesis and oxidative phosphorylation were the five significantly represented pathways. Four differentially expressed proteins (siglec-6, calnexin, CD63 and S100-A8) related to inflammation, coagulation or immunoregulation were independently verified using western blot. Conclusions: The identification of key proteins carried by STBM may serve not only as a basis for better understanding and further exploring the etiology and pathogenesis of PE, but also as potential biomarkers and in providing targets for future therapy in PE, especially in early-onset severe PE(sPE).

2-Methoxyestradiol deficiency is strongly related to hypertension in early onset severe pre-eclampsia

2-Methoxyestradiol (2ME) deficiency leading to placental insufficiency has been related to pre-eclampsia (PE). Here we investigate whether 2ME is related to clinical profiles and vasoactive factors in early onset severe PE patients. 28 severe PE patients and 20 uncomplicated normal pregnant women, with gestational weeks between 24 and 32weeks, were recruited. All cases and controls had singleton pregnancies and were matched for maternal age, parity, body mass index, and gestational weeks. Plasma levels of 2ME, estradiol (E2), soluble Fms-like tyrosine kinase-1 (sFLT-1), endothelin-1 (ET-1), nitric oxide (NO) were determined. PE patients had significant lower 2ME [906(422-1768) vs. 2032(1400-2910)pg/mL, P=0.002], higher sFLT-1 [5.55(3.24-11.22) vs. 3.13(2.17-5.36)ng/mL, P=0.015] and higher NO [122.40(72.92-168.23) vs. 45.83(25.52-61.46)μmol/L, P=0.0008] levels in their plasma than the controls. In the PE group, plasma 2ME level correlated negatively with systolic pressure (r=-0.48, P=0.012), diastolic pressure (r=-0.52, P=0.007) and mean arterial pressure (r=-0.54, P=0.005) even after controlling for maternal age; 2ME level did not correlate with proteinuria, plasma levels of E2, sFLT-1, ET-1 or NO. In the control group, plasma 2ME level did not correlate with any of the above clinical profiles or laboratory measurements. 2ME levels were markedly lower in early onset severe PE and they correlated inversely with blood pressure only in women with PE. Although we cannot tell whether lower 2ME level is the causation or the result of PE, our study provides clinical evidences that 2ME deficiency is strongly related to hypertension in early onset severe PE patients.

617: The association of VDR and angiogenic potential in early onset severe preeclampsia (EOSPE)

early onset severe preeclampsia (EOSPE) Angela Hawk, Satomi Kohno, Donna Johnson, Christopher Robinson Medical University of South Carolina, Obstetrics and Gynecology, Charleston, SC, Medical University of South Carolina, Hollings Marine Laboratory, Charleston, SC OBJECTIVE: Both pro and antiangiogenic factors are essential for normal placentation. Recent cardiovascular literature has revealed the important role of vitamin D in angiogenesis. Vitamin D deficiency has been linked with both increased risk for preeclampsia and intrauterine growth restriction (IUGR) in patients with EOSPE. Our goals were to identify the association between vitamin D signal, angiogenesis, IUGR and EOSPE. mRNA expression in EOSPE placenta was compared by race and IUGR. Vitamin D receptor(VDR), vascular endothelial growth factor (VEGF), placental growth factor(PlGF), retinoid X receptor(RXR), and soluble fms-like tyrosine kinase(sFlt-1) mRNA were quantified by real-time PCR(Q-PCR). STUDY DESIGN: RNA was extracted from placental samples (n 32) and quality/quantity verified via gel electrophoresis; non-contamination of genomic DNA was validated by Q-PCR. Primers were chosen via a literature/database search for genes of interest and housekeeping genes. RNA samples were reverse-transcribed, and expression levels quantified by comparison with serially diluted standard samples with known concentrations of target cDNA. Statistical analysis was performed with Wilcoxon Rank Sum tests and simple linear regression. RESULTS: African Americans (AA) showed significantly lower expression levels of sFlt-1 than Caucasians(C). VEGF expression level was lower in AA than in C, although it was not statistically significant (p 0.09). Presence of IUGR did not show any effects on mRNA expression. VDR expression was positively correlated with PlGF, sFlt-1, RXR-A and RXR-B, but not with VEGF. CONCLUSION: These associations suggest that Vitamin D signal could be responsible for an increase in both proand antiangiogenic factors. mRNA expression levels do not simply equate to amount of translated protein, indicating that the relationship of VDR to race and IUGR in EOSPE patients represents a more complex pathway. More investigation on vitamin D and angiogenesis in placenta is required to better understand its relationship with EOSPE. 618 Persistent urinary podocyte loss after preeclamptic pregnancies may be a possible mechanism of chronic renal injury Angelica Garrett, Iasmina Craici, Wendy White, Carl Rose, Brian Brost, Steven Wagner, Joseph Grande, Vesna Garovic Mayo Clinic College of Medicine, Maternal Fetal Medicine, Rochester, MN, Mayo Clinic College of Medicine, Hypertension and Nephrology, Rochester, MN OBJECTIVE: Studies show that proteinuria in preeclampsia is associated with podocyturia. Epidemiological studies have shown that preeclampsia is associated with future proteinuria and renal disease. Little is known about the resolution of podocyturia from time of delivery to 6wks postpartum. We postulate that persistent urinary podocyte loss after preeclamptic pregnancies may lead to proteinuria and chronic renal injury. STUDY DESIGN: The diagnoses of preeclampsia and HELLP were confirmed using standard clinical criteria. Random urine samples were obtained within 24hrs prior to delivery and 5-8wks postpartum (on average, 44 7d and 43 4d after delivery for cases and controls, respectively). Urine sediments were cultured for 24hrs to select for viable cells. Podocin staining was used to identify podocytes and podocyturia was expressed as a ratio of the number of podocytes to the creatinine (Cr) content of the respective urine sample. RESULTS: Delivery samples were obtained from 15 patients in the PE/ HELLP group and 23 normotensive controls. Postpartum samples were available for 10 of 15 cases and 18 of 23 controls. At delivery, patients with PE/HELLP had significantly higher proteinuria, (median 0.78g/24hrs; IQR 0.16-1.21) than normotensive controls (median 0.09g/24hrs; IQR 0.07-0.2). Podocyturia was present in all patients with PE/HELLP (median 0.77 podocytes/mg Cr; IQR 0.28-1.78) and in one patient (0.06 podocytes/mg Cr) from the control group. Postpartum proteinuria was similar between women with PE/HELLP (median 0.03g/24hrs; IQR 0.02-0.04) and those with normotensive pregnancies (median 0.03g/24hrs; IQR 0.02-0.05). Podocyturia was present in 3 of 10 women with PE/HELLP (median 0.63 podocytes/mg Cr; IQR 0.43-1.14) and in none of the normotensive controls. CONCLUSION: Persistent urinary podocyte loss after preeclamptic pregnancies may constitute a marker of ongoing renal injury. Longitudinal studies of the time course alteration of urinary podocyte loss after the affected pregnancies are needed. VDR and angiogenic factors