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.

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.

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.

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.

Prediction of adverse neonatal outcome at admission for early-onset preeclampsia with severe features.

BACKGROUND: Preeclampsia remains the leading cause of maternal morbidity and mortality. Consequently, research has focused on validating tools to predict maternal outcomes regarding clinical and biochemical features from the maternal compartment. However, preeclampsia also leads to neonatal complications due to placental insufficiency and prematurity, being the early-onset type associated with the poorest outcome. Hence, it is imperative to study whether these existing tools can predict adverse neonatal outcome. OBJECTIVE: To assess the predictive value for adverse neonatal outcome of Doppler ultrasound, angiogenic factors and multi-parametric risk-score models in women with early-onset severe preeclampsia. STUDY DESIGN: This is a prospective cohort study of consecutive singleton pregnancies complicated by early-onset (developed before 34 week's gestation) severe preeclampsia. RESULTS: 63 women with early-onset severe preeclampsia, 18 (28.6%) presented an adverse neonatal outcome. Placental growth factor (PlGF) showed the best discrimination between neonatal outcomes among angiogenic factors. PREP-L score is a multi-parametric risk-score for the prediction of complications in early-onset preeclampsia which includes maternal characteristics and clinical and analytical data obtained at admission. Good predictive values for the prediction of neonatal complications were found with the combination of PREP-L score with advanced Doppler (AUC ROC 0.9 95% CI 0.82-0.98]) and with PlGF levels (AUC ROC 0.91 [95% CI 0.84-0.98]). CONCLUSIONS: The combination of maternal risk scoring (PREP-L score) with angiogenic factors or fetal Doppler ultrasound at the time of diagnosis of early-onset preeclampsia with severe features performs well in predicting adverse neonatal outcome.

Conservative management of early-onset severe preeclampsia: comparison between randomized and observational studies a systematic review.

OBJECTIVE: To compare maternal and perinatal outcomes between randomized trials and observational studies in which conservative management was performed for more than 48 h in patients with early-onset severe preeclampsia. METHODOLOGY: We searched PubMed, LILACS, Cochrane and Google Scholar. The studies were divided in two groups: randomized and observational studies, from 1990 to 2018 that included patients with severe preeclampsia before 34 weeks of gestation with pregnancy prolongation ≥48 h but that did not include fetal growth restriction or HELLP syndrome at the beginning. The main variables recorded were maternal and perinatal complications. MAIN RESULTS: Forty-four studies met the inclusion criteria, and 5 of these were randomized. The average pregnancy prolongation was 9 days, with no difference between groups. Maternal complications were significantly more common in observational studies, RR = 0.71, 95% CI (0.54-0.93), p = .009. Perinatal complications were also significantly more common in observational studies (RR = 0.89, 95% CI (0.80-0.98), p = .01) at the expense of stillbirth and neonatal deaths. The percentages of cesarean sections were significantly higher in randomized studies, RR = 1.54, 95% CI (1.46-1.64). There were 2 maternal deaths, both in observational studies. CONCLUSION: Observational studies in which conservative management of early-onset preeclampsia is performed and do not include patients with fetal growth restriction or patients with HELLP syndrome and where at least 2 days of pregnancy prolongation is achieved are associated with significantly more maternal and perinatal complications.

Clinical significance of S100B protein in pregnant woman with early- onset severe preeclampsia.

OBJECTIVES: Preeclampsia is one of the most feared complications of pregnancy, which can progress rapidly to serious complications such as death of both mother and fetus. To present, the leading cause of preeclampsia is still debated. The purpose of this article was to explore the clinical significance of S100B protein, a kind of Ca2+ -sensor protein, in the early-onset severe preeclampsia. MATERIAL AND METHODS: Nine pregnant women with early-onset severe preeclampsia (the study group) and 13 healthy pregnant women (the control group) were included in this study. The level of S100B in the amniotic fluid, maternal blood, and umbilical cord blood were detected by enzyme-linked immunosorbent assay (ELISA) and surface plasmon resonance imaging (SPRi) methods. Diagnostic values of S100B for early-onset severe preeclampsia were assessed by Receiver Operating Characteristic (ROC) curve analysis. RESULTS: The levels of S100B in maternal blood and amniotic fluid in the study group were higher than those in the control group (p < 0.05). ROC curve analysis showed that S100B detected by SPRi method (SPRi-S100B) showed a cut-off level of 181 ng/mL with sensitivity of 100%, a specificity of 84.6%, and a Youden index of 0.846 in the maternal blood, which had better clinical significance and diagnostic value (at than that detected by ELISA (ELISA-S100B). CONCLUSIONS: The levels of S100B detected by SPRi in maternal blood can indicate early-onset severe preeclampsia and perinatal brain injury.

Added prognostic value of longitudinal changes of angiogenic factors in early-onset severe pre-eclampsia: a prospective cohort study.

OBJECTIVE: To assess in women with early-onset severe pre-eclampsia whether longitudinal changes in angiogenic factors improve the prediction of adverse outcome. DESIGN: Prospective cohort study. SETTING: Maternity units in two Spanish hospitals. POPULATION: Women with diagnosis of early-onset severe pre-eclampsia. METHODS: Levels of placental growth factor (PlGF), soluble fms-like tyrosine kinase (sFlt-) and sFlt-1/PlGF ratio were measured at admission and before delivery, and average daily change calculated. The association of longitudinal changes of angiogenic factors with the time interval to delivery and with complications was evaluated by logistic and Cox regression. MAIN OUTCOME MEASURES: Interval to delivery and composite of adverse outcomes. RESULTS: We included 63 women, of which 26 (41.3%) had a complication. Longitudinal changes of sFlt-1 were more pronounced in complicated pregnancies (median: 1047 versus 342 pg/ml/day; P = 0.04). On the multivariate analysis, the clinical risk score and sFlt-1 at admission explained 6.2% of the uncertainty for complication; the addition of sFlt-1 longitudinal changes improved this to 25.3% (P = 0.002). The median time from admission to delivery was 4 days (95% CI 1.6-6.04) in those in the highest quartile of sFlt-1 longitudinal changes versus 16 days (95% CI 12.4-19.6) in the remaining women (Log-rank test P < 0.001). CONCLUSIONS: Longitudinal changes in sFlt-1 maternal levels from admission for confirmed early-onset severe pre-eclampsia add to baseline characteristics in the prediction of adverse outcome and interval to delivery. TWEETABLE ABSTRACT: In early-onset severe pre-eclampsia, longitudinal changes in sFlt-1 levels improve the prediction of complications and interval to delivery.

Effect of magnesium sulfate combined with labetalol on serum sFlt-1/PlGF ratio in patients with early-onset severe pre-eclampsia.

The aim of the present study was to investigate the therapeutic effect of magnesium sulfate combined with labetalol on the early-onset severe pre-eclampsia (ES-PE) and explore the role of soluble fms-like tyrosine kinase-1 (sFlT-1), placental growth factor (PlGF), and sFlt-1/PlGF ratio in the treatment. A total of 164 ES-PE patients admitted to the Maternity and Child Health Care Hospital of Hubei (Wuhan, China) were assigned to this observational study. Among them, 83 patients were enrolled in group A and treated with magnesium sulfate combined with labetalol hydrochloride, and 81 patients were enrolled in group B and treated with magnesium sulfate. The therapeutic effect, adverse reactions and pregnancy outcomes in the two groups were analyzed. Serum sFlt-1 and PlGF concentrations, before and after treatment, were measured by enzyme-linked immunosorbent assay (ELISA). Receiver operating characteristic (ROC) curve analysis was performed to assess the predictive value of pre-treatment serum sFlt-1/PlGF ratio for the clinical outcome. The effective rate was significantly higher in group A than that in group B. Group A presented superior pregnancy outcomes over group B. The serum sFlt-1 concentration and sFlt-1/PlGF ratio after treatment were significantly lower than those before treatment in groups A and B, whereas PlGF concentration was significantly higher after treatment in both groups. After treatment, group A had markedly lower serum sFlt-1 concentration and sFlt-1/PlGF ratio than group B, and markedly higher PlGF concentration than group B. The area under curve (AUC) of serum sFlt-1/PlGF ratio before treatment for the prediction of the clinical efficacy was 0.737. In conclusion, magnesium sulfate combined with labetalol could be effectively used for the treatment of ES-PE. The results of ELISA revealed that the balance of sFlT-1 and PlGF was improved after treatment and the sFlT-1/PlGF ratio was decreased. The assessment of sFlt-1/PlGF ratio before treatment was shown to have a certain predictive value for the efficacy of ES-PE treatment.

Early onset severe preeclampsia and eclampsia in a low-resource setting, Mpilo Central Hospital, Bulawayo, Zimbabwe.

OBJECTIVES: Early-onset severe preeclampsia is associated with significant maternal and perinatal morbidity and mortality especially in low-resource settings, where women have limited access to antenatal care. This dataset was generated from a retrospective cross-sectional study carried out at Mpilo Central Hospital, covering the period February 1, 2016 to July 30, 2018. The aim of the study was to determine the incidence of early-onset severe preeclampsia and eclampsia, and associated risk factors in a low-resource setting. The reason for examining the incidence of preeclampsia specifically in a low-resource setting; was to document it as women in these settings appear to suffer from poor outcomes. DATA DESCRIPTION: The dataset contains data of 238 pregnant women who had a diagnosis of early onset severe preeclampsia/eclampsia. There were 243 babies from singleton and twin gestations. There were five sets of twins. There were 21,505 live births during the study period giving an incidence of 1.1%. The dataset contains data on maternal socio-demographic, signs and symptoms, therapeutic interventions and mode of delivery, adverse outcomes characteristics, and fetal characteristics. This large dataset can be used to calculate the incidence and risk factors for adverse maternal and fetal outcomes or develop predictive models in severe preeclampsia/eclampsia.

Expectant management of early-onset severe preeclampsia: a principal component analysis.

BACKGROUND: Preeclampsia is a multisystem disorder that is characterized by hypertension with either proteinuria or end-organ dysfunction in both previously normotensive women and chronically hypertensive women. To identify the important influencing factors for early-onset severe preeclampsia, this study undertook to explore the associations between preeclampsia characteristics, along with the decreased latency and poor neonatal outcomes during expectant management of severe preeclampsia before 34 weeks of gestation. METHODS: A total of 213 patients were retrospectively studied. Pregnancy outcomes in terms of maternal complications and neonatal outcomes were determined. Statistical analysis was performed by principal component analysis, Student's t-test, and Pearson correlation analysis. RESULTS: Neonatal mortality was influenced by gestational age at delivery and birth weight. The main factors that influenced pregnancy outcome were gestational age at diagnosis, the 24-h urine protein level, the plasma albumin level, and hydrothorax plus ascites. When the gestational age at diagnosis was 25 weeks, and 4/7 days, the probability that the pregnancy would be classified into group 2 with 79.3% neonatal survival was almost 50%. Only the plasma albumin level and hydrothorax plus ascites affected prolongation. CONCLUSIONS: Plasma albumin level and hydrothorax plus ascites should be considered seriously, as they may be a reason to terminate the expectant management of early-onset severe preeclampsia. Given its unsatisfactory pregnancy outcomes, expectant management should be reconsidered before 25 weeks and 4/7 days.

Expression and significance of TNF?α and M?CSF in placenta tissue of early severe preeclampsia / 中国综合临床

Objective To investigate the expression and clinical significance of macrophage colony stimulating factor ( M?CSF ) and tumor necrosis factor α ( TNF?α ) in placenta of early onset severe preeclampsia (PE)??Methods Immunohistochemical SP method was used to detect the expression of M?CSF and TNF?α in 77 cases paraffin specimens from Department of Pathology,First Affiliated Hospital of Henan University of Science and Technology from September 2015 to September 2017,including 35 cases of early?onset severe PE,42 cases of late?onset severe PE and 30 cases of normal pregnant women??Results (1)The positive expression rates of M?CSF in control group,late?onset severe PE group and early?onset severe PE group were 30%(9／30),61??90%(26／42),82??86%(29／35),respectively??The difference was statistically significant ( χ2 ＝ 18??90, P＜0??05)??The positive expression rates of early?onset severe PE group were significantly higher than those in control group (χ2＝18??59,P＜0??05),and the difference was statistically significant????The positive expression of early?onset severe PE group was higher than that of late?onset severe PE group,and the difference was statistically significant (χ2＝4??017,P＜0??05)??(2) The positive expression rates of TNF?α in control group,late?onset severe PE group and early?onset severe PE group were 33??33%(10／30),69??05%(29／42),91??43%(32／35),respectively??The difference was statistically significant (χ2＝30??21,P＜0??05)??The positive expression of TNF?α in early?onset severe PE group was significantly higher than that in control group (χ2＝21??37,P＜0??05),and the difference was statistically significant??The positive expression of M?CSF and TNF?a in early?onset severe PE group was higher than that in late?onset severe PE group,and the difference was statistically significant (χ2＝4??529,P＜0??05); (3) The expression of M?CSF and TNF?α was positively correlated in PE (r＝0??441,P＝0??000)??Conclusion Placental damage is higher in early?onset severe PE,and is related to the severity of the disease??The levels of M?CSF and TNF?alpha in placenta of PE patients may play a synergistic role in the occurrence and development of PE??

Correlation of miRNA and VEGF expression with the outcome of early-onset severe preeclampsia in patients receiving expectant treatment.

The present study was planned to explore the relationship between miRNA and VEGF expression in serum as well as placenta tissue with the outcome of early-onset severe preeclampsia (EOSP) in patients receiving expectant treatment. Sixty EOSP patients who had expectant treatment indications were divided into the success group (n = 46) and the failure group (n = 14) according to the pregnancy outcomes. miR-210 and miR-155 expression levels were studied in serum, ante partum, and in placenta tissue. The vascular endothelial growth factor (VEGF) and soluble VEGF receptor 1 (sFlt-1) expression levels were also explored. miR-210 and miR-155 expression levels in serum and placenta tissue before treatment, ante partum, and after accouchement of the success group were significantly lower than those of the failure group. Further, VEGF expression levels in serum and placenta tissue before treatment, ante partum, and after accouchement of the success group were significantly higher than those of the failure group. However, sFlt-1 expression levels in the success group showed a decrease in comparison to the failure group. The increase of miR-210, miR-155 levels, sFlt-1 levels, and the decrease of VEGF levels in EOSP patients might be correlated with the failure of expectant treatment.

Risk factors for cardiopulmonary dysfunction in early-onset severe pre-eclampsia.

OBJECTIVE: To explore associations between patient characteristics and cardiopulmonary function among patients with early-onset severe pre-eclampsia being treated with expectant management. METHOD: The present retrospective study included patients who received expectant management for early-onset pre-eclampsia between January 1 and December 31, 2014 at Shanghai Jiao Tong University School of Medicine, China. Patients were divided into two groups based on cardiopulmonary function, a decompensatory group and a normal group. The clinical characteristics of patients in the two groups were compared by binary logistic regression analysis and using the Student t test. RESULTS: Data from 93 patients were included in the analysis. Serum creatinine levels (P=0.017), ascites (P=0.001), and increased proteinuria (P=0.015) were associated with decompensation of cardiopulmonary function during early-onset severe pre-eclampsia. Hypoproteinemia was associated with significantly increased odds of ascites occurring (odds ratio 3.16; 95% confidence interval 1.34-7.44) and the mean serum albumin level was higher in patients without ascites (P<0.001). CONCLUSIONS: Renal insufficiency and ascites were associated with cardiopulmonary dysfunction. Ascites should receive greater medical attention during the expectant management of early-onset severe pre-eclampsia.

Glicanos de la vellosidad trofoblástica en la anemia ferropénica y la preeclampsia grave / Glycans in villus trophoblast in iron deficiency anemia and early-onset severe preeclampsia

Glycoproteins attached to cell membrane of syncytiotrophoblast are in close contact with maternal blood, thus these molecules could participate in cell-to-cell communication and biological functions involving ligand-receptors in the maternal-fetal interphase. The attached glycans are involved in the stability, folding and exportation of the protein towards the cell membrane. The objective of this study was to characterize the glycan profile of third trimester placental villi obtained from pregnant women with early-onset severe preeclampsia and gestational anemia compared with normal pregnant women. Protein extracts from placental villi were used in lectin blot assays. -2,3 N- and O-linked sialic acid was over-expressed in villous of severe preeclamptic placentas measured by MAA lectin staining. High mannose glycans and Gal-GlcNAc patterns were also increased in severe preeclampsia compared with the other groups. These findings can explain changes in the cell membrane expression of glycoproteins.

Introducción: Las glicoproteínas de la membrana del sincitiotrofoblasto (STB) se encuentran en contacto con la sangre materna, por lo que pueden participar en la comunicación en la interface materno-fetal. Objetivo: caracterizar patrones de glicanos de la vellosidad trofoblástica de mujeres sanas, anémicas por deficiencia de hierro y preeclámpticas graves de inicio temprano. Materiales y métodos: se obtuvieron extractos proteínicos de vellosidad placentaria de tercer trimestre y se determinó la expresión de patrones de glicanos, usando lectinas. Para la comparación de los grupos se utilizó la prueba de Kruskal-Wallis. Resultados: Se encontró una sobreexpresión en los patrones de glicosilación Gal-GlcNAc, manosa y ácido siálico α2-3 en el grupo con preeclampsia. Conclusiones: El aumento en los patrones Gal-GlcNAc, alta manosilación y ácido siálico α2-3, en proteínas de vellosidad placentaria en los pesos moleculares encontrados, pudiera explicar cambios en la expresión de proteínas de membrana del STB.

First trimester placental retinol-binding protein 4 (RBP4) and pregnancy-associated placental protein A (PAPP-A) in the prediction of early-onset severe pre-eclampsia.

OBJECTIVE: In a retrospective case-control study, we examined the levels of placental retinol-binding protein 4 (RBP4) and pregnancy-associated placental protein A (PAPP-A) in first-trimester maternal serum samples as well as maternal characteristics to predict early-onset and severe pre-eclampsia. METHODS: In this retrospective case-control study, we identified females who delivered a singleton pregnancy on or after 24 weeks' gestation from 2003 to 2010 at Oulu University Hospital and had a retrospective first trimester trisomy screening, including serum PAPP-A measurement. Within this cohort, we identified 65 females who experienced early onset pre-eclampsia (EO-PE) and 742 controls who had uncomplicated deliveries. Retrospectively, we thawed all previously collected serum samples to measure placental retinol binding protein 4 (RBP4). PAPP-A and RBP4 were measured using automatic immunoassay systems and converted to multiples of the median (MoMs). Logistic regression analysis was performed to determine whether these biomarkers separately and in combination with maternal characteristics (maternal age, weight and smoking status) can be used to predict the development of early onset pre-eclampsia. RESULTS: The expected log(10) PAPP-A concentration and the expected log(10) RBP4 concentration in the control group were both affected by maternal weight and smoking status. The expected log(10) PAPP-A concentration was also affected by gestational age (GA). RBP4 levels in first-trimester serum were significantly higher in females who subsequently developed EO-PE outcome compared to those with normal pregnancy outcome (1.14 vs. 1.01 MoMs, p<0.0001). Maternal serum PAPP-A levels from the same pregnancy period were significantly lower in the EO-PE group compared to controls (0.80 vs. 1.05 MoMs, p=0.005). The risk model including maternal characteristics with PAPP-A log(10) MoM and RBP4 log(10) MoM had the best EO-PE prediction ability. It detected 34% (23%-46%) of females with subsequent EO-PE with a 10% false positive rate. CONCLUSION: This study showed that first-trimester maternal serum RBP4 was significantly increased and that PAPP-A decreased in pregnancies that ended in EO-PE compared to normal pregnancies. Thus, these markers may be useful members in a panel of markers for the early detection of early-onset and severe pre-eclampsia.

Role of osteoprotegerin gene variants in early-onset severe pre-eclampsia.

AIM: The aim of this study was to detect the role of osteoprotegerin (OPG) gene variants in early-onset severe pre-eclampsia. MATERIAL AND METHODS: The associations of 163A/G (rs3102735) and 950T/C (rs2073617) polymorphisms of OPG with pre-eclampsia (60 cases of early-onset severe pre-eclampsia and 91 cases of late-onset pre-eclampsia), as well as with the clinical manifestations of individuals, were evaluated. RESULTS: Data showed lower frequencies of TC and TC + CC genotypes and C allele of 950T/C in the early-onset group than those of the control and late-onset groups (P = 0.003; P = 0.002; P = 0.005; P = 0.031; P = 0.021; P = 0.022). However, no significant differences were found in genotype and allele frequencies between the late-onset and control groups. Moreover, no significant differences were observed in the genotype and allele frequencies of 163A/G polymorphism among the three groups. In the early-onset group, 950T/C TC + CC genotype carriers exhibited significantly lower systolic blood pressure ([147.25 ± 11.89] mmHg) and 24-h urine protein ([2.46 ± 0.92] g) than the TT carriers ([165.88 ± 20.39] mmHg, [3.64 ± 0.81] g) (P = 0.003; P = 0.001, respectively). Serum creatinine was significantly higher in women with the 163A/G AG + GG genotypes ([82.31 ± 11.66] µmol/L) than in those with the AA genotype ([71.90 ± 16.85] µmol/L) (P = 0.003). CONCLUSION: This study implicates that OPG gene variants may be associated with early-onset severe pre-eclampsia.

Clinical Study on Tianma Gouteng Decoction Combined with Routine Western Therapy in the Treatment of Early Onset Severe Pre-eclampsia / 中国中医药信息杂志

Objective To observe clinical efficacy of Tianma Gouteng Decoction combined with Western medicine for early onset severe pre-eclampsia. Methods Sixty patients were randomly divided into treatment group with 30 cases and control group with 30 cases. Two groups were both given the routine Western therapy, while the treatment group was added with Tianma Gouteng Decoction. Indicators were observed and compared between two groups including blood pressure, 24 h UAE, D-dimer, fibrinogen and their effects on pregnancy. Results Compared with the control group, the blood pressure, 24 h UAE, fibrinogen, D-dimer, hypoproteinemia, and liver and kidney function were reduced obviously in the treatment group (P<0.05);fibrinogen and D-dimer of control group were not changed significantly;gestational weeks of treatment group were extended (15.2 ± 4.8)d, and neonatal asphyxia was 7 cases;gestational weeks of control group were extended (9.3 ± 2.2)d, and neonatal asphyxia was 11 cases. There was no significant difference about cesarean section rate between the two groups. Conclusion Tianma Gouteng Decoction combined with Western medicine for treatment of early onset severe pre-eclampsia have better clinical efficacy.

Sera from early-onset, severely preeclamptic women directly modulate HLA-E expression in the EA.hy296 endothelial cell line.

The expression of endothelial HLA-E in the context of the systemic inflammatory response observed in preeclampsia has not been established. An experimental study was designed to determine the effect of the sera of pregnant women on the expression of HLA-E in EA.hy296 endothelial cells. First, measurements of protein fractions were performed in sera from early-onset, severely preeclamptic women without HELLP syndrome, in which there was no significant difference in total proteins between the groups, but a reduced level of plasma albumin and an increase in α1-globulin were observed in both groups of pregnant women compared with non-pregnant women. Measurements of colloid osmotic pressure (COP) using a recalculated albumin/globulin ratio formula determined only a significant decrease in COP in all pregnant groups compared with non-pregnant women. The expression of membrane HLA-E was increased in EA.hy296 endothelial cells stimulated with sera of early-onset, severely preeclamptic women, while recombinant interferon-γ (IFN-γ) significantly reduced the expression of membrane HLA-E. Pro-inflammatory cytokines were measured by Luminex in the serum samples, and increased levels of tumor necrosis factor (TNF) and decreased levels of IFN-γ were observed in early-onset, severe preeclampsia compared with normal pregnancy. Moreover, soluble HLA-E was detected in these serum samples by Western blot and ELISA, but no significant difference was found. This raises the possibility that a systemic inflammatory response promotes a compensatory mechanism of COP balance in severe preeclampsia by release of inflammation-induced factors, including endothelial HLA-E. Evidence is now provided regarding HLA-E expression by EA.hy296 cells.

Population-based biomarker screening and the development of severe preeclampsia in California.

OBJECTIVE: The purpose of this study was to examine the relationship between second-trimester maternal serum biomarkers and the development of early- and late-onset severe preeclampsia in euploid pregnancies. STUDY DESIGN: Included were 136,139 pregnancies that obtained second-trimester prenatal screening through the California Prenatal Screening Program with live births in 2006-2008. We identified severe preeclampsia diagnoses from hospital discharge records. We used log binomial regression to examine the association between abnormal second-trimester maternal serum biomarkers and the development of severe preeclampsia. RESULTS: Approximately 0.9% of all women (n = 1208) in our sample experienced severe preeclampsia; 329 women at <34 weeks' gestation and 879 women ≥34 weeks' gestation. High levels of alpha fetoprotein (AFP), human chorionic gonadotropin, inhibin (multiple of the median, ≥95th percentile), and low unconjugated estriol (multiple of the median, ≤5th percentile), were associated with severe preeclampsia (relative risk, 2.5-11.7). Biomarkers were more predictive of early-onset severe preeclampsia (relative risk, 3.8-11.7). One in 9.5 pregnancies with combined high AFP, inhibin, and low unconjugated estriol levels experienced severe early-onset preeclampsia compared with 1 in 680.5 pregnancies without any abnormal biomarkers. CONCLUSION: The risk of the development of severe preeclampsia increases for women with high second-trimester AFP, human chorionic gonadotropin, inhibin, and/or low unconjugated estriol; this is especially true for early-onset severe preeclampsia. When abnormal biomarkers co-occur, risk dramatically increases. Although the screening value of second-trimester biomarkers is low, abnormal biomarkers, especially when occurring in combination, appear to indicate placental dysfunction that is associated with the development of severe preeclampsia.