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.
CONCLUSIONS: 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.

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.

OBJECTIVE: 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.
METHODS: 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.
CONCLUSIONS: 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.

UNASSIGNED: To determine whether maternal pre-pregnancy body mass index is associated with preeclampsia with severe features, categorized as early- or late-onset.
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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.

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.
METHODS: 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.

OBJECTIVE: 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.
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.

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.
METHODS: 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.
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.
CONCLUSIONS: 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.

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.

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.

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.
METHODS: 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.
CONCLUSIONS: 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.