The Relationship between the Level of Coagulative Function Hypertensive Disorder Complicating Pregnancy.

BACKGROUND AND AIM: Preeclampsia, a pregnancy complication associated with significant maternal and perinatal mortality and morbidity, has been found to be closely linked to dysfunction in the blood coagulation-fibrinolysis system. However, the relationship between hematologic data and severity and onset time of preeclampsia remains unclear. This study aimed to identify specific hematologic parameters in both preeclamptic and normotensive pregnant women and determine their potential significance in the pathogenesis of preeclampsia. MATERIALS AND METHODS: A total of 112 patients with gestational hypertension disease were divided into two groups: early-onset preeclampsia (32 cases) and late-onset preeclampsia (80 cases). A control group of 82 normotensive pregnant women matched for age and parity was also selected. Blood samples were collected from all participants to test for specific hematologic parameters. RESULTS: Mild and severe preeclampsia were associated with lower hemoglobin level (P = 0.01 and P = 0.03, respectively), higher mean platelet volume (P = 0.01 and P = 0.01, respectively) and fibrinogen (P = 0.01 and P = 0.01, respectively), and shorter prothrombin time (P = 0.02 and P = 0.01, respectively) and activated partial thromboplastin time (P = 0.01 and P = 0.02, respectively). CONCLUSION: These findings have provided evidence on the hematologic coagulative actors in the pathogenesis and severity of preeclampsia.

An in vitro study of coagulation evaluation in obstetric hemorrhage for pregnancy-induced hypertension with coagulation and platelet function analyzer.

This study aimed to establish in vitro hemodilution and resupplementation assays for obstetric hemorrhage in pregnancy-induced hypertension (PIH) and to monitor the coagulation function dynamically using a coagulation and platelet function analyzer. Forty-seven singleton pregnant women were divided into normal (n = 24) and PIH (n = 23) groups. Peripheral blood samples were used to construct the assays, and the activated clotting time (ACT), clotting rate (CR), and platelet function index (PF) were measured. The results showed that the baseline ACT was higher in the PIH group (p < 0.01). Hemodilution assays showed decreased ACT and increased CR and PF, with ACT changes significantly lower in the PIH group (p < 0.05). CR changed most in both groups at lower dilution ratios (35% to 50%), while ACT changed most at a higher dilution ratio (75%). In the resupplementation assay, ACT exhibited the most significant response. The analyzer effectively detected differences between pregnant women with and without PIH. Thus, we need to pay more attention to the changes of ACT in the actual clinical application to assess the coagulation status of parturients.

The association between serum uric acid and low birth weight in advance maternal age women with hypertension: An observational study.

In China, the implementation of 2-child policy since 2015 entitles increasing number of advanced maternal age. Recently, Chinese hypertensive disorders of pregnancy (HDP) in advanced-age women have attracted significant clinical and epidemiological research interest. Previous studies have shown an association between serum uric acid (SUA) levels and low birth weight (LBW) in children. Several studies have reported that advanced maternal age is a risk factor for many complications in pregnancy, including LBW. However, it remains unclear whether SUA affects LBW risk in advanced maternal age mothers with hypertensive diseases. The study was observational in nature. A total of 692 advanced maternal age with hypertension were enrolled in our study. A variety of demographic and vital sign data, laboratory test results, and pregnancy outcomes were collected. Children born with LBW served as the clinical endpoint. On admission, blood samples were taken, and women with advanced maternal ages were divided into 2 groups based on their SUA levels. In order to investigate the association between SUA and LBW, a logistic regression model was used. E-value analysis was used to determine the residual unmeasured confounding. The mean SUA level was increased in advanced maternal age patients with HDP. Of 692 newborns, 244 (35.26%) have LBW. With possible confounders adjusted, high SUA levels were independent risk factors for LBW (odds ratio [OR]2.88, 95% confidence intervals [CI]1.22-6.81), multivariate logistic regression analysis using SUA as a continuous variable recapitulated the pattern (OR 1.01, 95% CI 1.00-1.01). In addition, SUA levels in women with advanced maternal age and hypertension were linearly related to LBW incidence. According to this study, SUA levels in patients with advanced maternal age and HDP are associated with LBW incidence.

Pregnancy induced hypertension and umbilical cord blood DNA methylation in newborns: an epigenome-wide DNA methylation study.

OBJECTIVIES: Pregnancy induced hypertension (PIH) syndrome is a disease that unique to pregnant women and is associated with elevated risk of offspring cardiovascular diseases (CVDs) and neurodevelopmental disorders in their kids. Previous research on cord blood utilizing the Human Methylation BeadChip or EPIC array revealed that PIH is associated with specific DNA methylation site. Here, we investigate the whole genome DNA methylation landscape of cord blood from newborns of PIH mother. METHODS: Whole-genome bisulfite sequencing (WGBS) was used to examine the changes in whole genome DNA methylation in the umbilical cord blood of three healthy (NC) and four PIH individuals. Using methylKit, we discovered Hypo- and hyper- differentially methylated probes (DMPs) or methylated regions (DMRs) in the PIH patients' cord blood DNA. Pathway enrichments were assessed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment assays. DMPs or DMRs relevant to the immunological, neurological, and circulatory systems were also employed for enrichment assay, Metascape analysis and PPI network analysis. RESULTS: 520 hyper- and 224 hypo-DMPs, and 374 hyper- and 186 hypo-DMRs between NC and PIH group, respectively. Both DMPs and DMRs have enhanced pathways for cardiovascular, neurological system, and immune system development. Further investigation of DMPs or DMRs related to immunological, neurological, and circulatory system development revealed that TBK1 served as a hub gene for all three developmental pathways. CONCLUSION: PIH-associated DMPs or DMRs in umbilical cord blood DNA may play a role in immunological, neurological, and circulatory system development. Abnormal DNA methylation in the immune system may also contribute to the development of CVDs and neurodevelopment disorders.

First-trimester serum biomarkers in twin pregnancies and adverse obstetric outcomes-a single center cohort study.

PURPOSE: This study aimed to determine the association of first-trimester maternal serum biomarkers with preterm birth (PTB), fetal growth restriction (FGR) and hypertensive disorders of pregnancy (HDP) in twin pregnancies. METHODS: This is a retrospective cohort study of twin pregnancies followed at Maternidade Dr. Alfredo da Costa, Lisbon, Portugal, between January 2010 and December 2022. We included women who completed first-trimester screening in our unit and had ongoing pregnancies with two live fetuses, and delivered after 24 weeks. Maternal characteristics, pregnancy-associated plasma protein-A (PAPP-A) and ß-human chorionic gonadotropin (ß-hCG) levels were analyzed for different outcomes: small for gestational age (SGA), gestational hypertension (GH), early and late-onset pre-eclampsia (PE), as well as the composite outcome of PTB associated with FGR and/or HDP. Univariable, multivariable logistic regression analyses and receiver-operating characteristic curve were used. RESULTS: 466 twin pregnancies met the inclusion criteria. Overall, 185 (39.7%) pregnancies were affected by SGA < 5th percentile and/or HDP. PAPP-A demonstrated a linear association with gestational age at birth and mean birth weight. PAPP-A proved to be an independent risk factor for SGA and PTB (< 34 and < 36 weeks) related to FGR and/or HDP. None of the women with PAPP-A MoM > 90th percentile developed early-onset PE or PTB < 34 weeks. CONCLUSION: A high serum PAPP-A (> 90th percentile) ruled out early-onset PE and PTB < 34 weeks. Unless other major risk factors for hypertensive disorders are present, these women should not be considered candidates for aspirin prophylaxis. Nevertheless, close monitoring of all TwP for adverse obstetric outcomes is still recommended.

Maternal pregnancy hypertension impairs nitric oxide formation and results in increased arterial blood pressure in first-generation offspring female rats.

OBJECTIVES: Maternal endothelial dysfunction in pregnancy hypertension is related to impairment of nitric oxide (NO) formation. However, NO levels and hemodynamic repercussions on the female offspring remain unclear. Therefore, this study hypothesized that maternal pregnancy hypertension reduces circulating NO metabolites and increases arterial blood pressure in first-generation offspring female rats. STUDY DESIGN: Descendant female rats were distributed in four groups as follows: virgin offspring of normotensive (VN) and hypertensive (VH) mothers and pregnant offspring of normotensive (PN) and hypertensive (PH) mothers. Hemodynamic and biochemical analyses were performed. MAIN OUTCOME MEASURES: The systolic (SBP) and diastolic (DBP) blood pressure, heart rate (HR), and body weight were measured. NO metabolites in plasma, NO formation in human umbilical vein endothelial cells (HUVECs) incubated with plasma, and endothelial NO synthase (eNOS) expression in aortas were determined. RESULTS: Increased SBP, DBP, and reduced HR were found on the 60 days of life in the VH group, whereas the PH group showed increased SBP and HR on pregnancy day 7. All groups showed no differences in body weight gain and eNOS expression. Plasma levels of NO metabolites were increased in the PN compared to the other groups. Increases in the NO formation were greater in HUVECs incubated with plasma from VN and PN groups compared to the VH and PH groups. CONCLUSIONS: Female virgin and pregnant first-generation offspring rats from hypertensive pregnant mothers may have negative cardiovascular repercussions featured by increases in SBP, and possibly impaired NO formation is involved.

Early-pregnancy N-terminal pro-brain natriuretic peptide level is inversely associated with hypertensive disorders of pregnancy diagnosed after 35 weeks of gestation.

Hypertensive disorders of pregnancy (HDP) are among the major causes of high maternal and fetal/neonatal morbidity and mortality rates. Patients with HDP have significantly elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) levels at diagnosis; however, the NT-proBNP levels during early pregnancy are largely unknown. This study aimed to validate the association between HDP and NT-proBNP levels. This retrospective study evaluated 103 pregnant women who developed HDP diagnosed after 35 weeks of gestation and 667 who did not. The HDP group had significantly lower early-pregnancy NT-proBNP levels than the without HDP group. However, the two groups did not significantly differ in terms of the late-pregnancy NT-proBNP levels. After adjusting for confounding factors such as age, body mass index, parity, and blood pressure levels, high early-pregnancy NT-proBNP levels were associated with a lower HDP risk. Early-pregnancy NT-proBNP levels ≥ 60.5 pg/mL had a negative predictive value of 97.0% for ruling out HDP, with a sensitivity of 87.4% and specificity of 62.5%. In conclusion, elevated early-pregnancy NT-proBNP levels were associated with a lower HDP risk. Moreover, a cutoff point of ≥ 60.5 pg/mL for early-pregnancy NT-proBNP levels had a high negative predictive value and sensitivity for ruling out HDP. These findings can provide new clinical implications.

Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) and associations with hypertensive disorders of pregnancy in the Atlanta African American Maternal-Child cohort.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are man-made chemicals that are slow to break down in the environment and widely detected in humans. Epidemiological evidence suggests that prenatal exposure to perfluorooctanoic acid (PFOA), a legacy PFAS, is linked to gestational hypertension and preeclampsia. However, the relationship between other PFAS, which are structurally similar, and these outcomes remains largely understudied, despite biologic plausibility. Here, we examined associations between serum PFAS mixtures in relation to hypertensive disorders of pregnancy within a birth cohort of African Americans. METHODS: Participants in the present study were enrolled in the Atlanta African American Maternal-Child cohort between 2014 and 2020 (n = 513). Serum samples collected between 8 and 14 weeks gestation were analyzed for four PFAS. Logistic regression was used to assess associations between individual natural log transformed PFAS and specific hypertensive disorders of pregnancy (preeclampsia, gestational hypertension), while quantile g-computation was used to estimate mixture effects. Preeclampsia and gestational hypertension were treated as separate outcomes in individual models. All models were adjusted for maternal education, maternal age, early pregnancy body mass index, parity, and any alcohol, tobacco, or marijuana use. RESULTS: The geometric mean of PFOS and PFHxS was slightly lower among those with preeclampsia relative to those without a hypertensive disorder (e.g., geometric mean for PFOS was 1.89 and 1.94, respectively). Serum concentrations of PFAS were not strongly associated with gestational hypertension or preeclampsia in single pollutant or mixture models. For example, using quantile g-computation, a simultaneous one quartile increase in all PFAS was not associated with odds of gestational hypertension (odds ratio = 0.86, 95% CI = 0.60, 1.23), relative to those without a hypertensive disorder of pregnancy. CONCLUSIONS: In this birth cohort of African Americans, there was no association between serum PFAS measured in early pregnancy and hypertensive disorders of pregnancy, which may be reflective of the fairly low PFAS levels in our study population.

Serum levels of sirtuins, leptin and adiponectin in women with pregnancy-induced hypertension.

INTRODUCTION: Pregnancy-induced hypertension (PIH) and preeclampsia (PE) are associated with disturbed maternal inflammatory response, oxidative stress and vascular endothelial cell dysfunction. Obesity is one of risk factors of PE. Leptin is elevated in obesity and its level correlates positively with the amount of adipose tissue. In contrast, adiponectin levels are decreased in obesity. Sirtuins are expressed in the placenta, however their role in pregnancy-related pathology in humans is not known. AIM OF THE STUDY: The aim of our study was to measure serum concentrations of selected sirtuins, adiponectin and leptin in healthy pregnancy and in women with PIH. MATERIALS AND METHODS: The study included 70 women: 38 healthy pregnant women and 32 women with PIH. Blood samples were obtained between the 20th and 40th week of gestation. Serum levels of sirtuins 1, 3, 6, leptin and adiponectin were measured with ELISA. RESULTS: Leptin levels were significantly higher in PIH group as compared to the controls and correlated positively with BMI. Highest leptin levels were observed in women who needed a cesarean section. Levels of sirtuins 1, 3 and 6 were similar in both groups and did not correlate with BMI. CONCLUSIONS: High leptin levels in PIH women during 3rd trimester might be helpful to predict the necessity for a caesarian section. Blood levels of sirtuins 1, 3 and 6 measured after the 20th week of gestation cannot be regarded as a single diagnostic test for PIH or preeclampsia. More studies to clarify significance of sirtuins in PIH and PE development and diagnosis are needed.

N-terminal prohormone of brain natriuretic peptide in gestational hypertension and preeclampsia - State of the art.

N-terminal prohormone of brain natriuretic peptide (NT-proBNP) is a non-active prohormone secreted by ventricular cardiomyocytes into the circulation in response to ventricle overload, mainly due to increased blood volume. The changes in NT-proBNP levels during pregnancy have been investigated in multiple studies. In the case of hypertensive disorders of pregnancy, increased vasoconstriction leads to increased blood pressure and afterload. Together with the volume overload of pregnancy, it leads to higher NT-proBNP secretion. As hypertensive disorders of pregnancy are among the leading causes of prematurity and perinatal mortality, early prediction and diagnosis of gestational hypertension, and preeclampsia are essential for improving maternal and infant prognosis. NT-proBNP has been regarded as a potential biomarker of hypertensive disorders of pregnancy. In this review, we have thoroughly summarized the current data on the prognostic and diagnostic utility of NT-proBNP in patients with gestational hypertension and preeclampsia. NT-proBNP values may help distinguish between non-preeclamptic and preeclamptic patients, even if there are no significant differences in blood pressure. Moreover, in pregnancies complicated by preeclampsia, the value of increased NT-proBNP level is related to the stage and the severity of the disease. Further improvement of our knowledge about NT-proBNP as a diagnostic biomarker and a putative predictor of adverse cardiac events in women with hypertensive disorders of pregnancy should lead to better management of these patients.

Expression of long non-coding RNA GAS5 by first trimester screening predicts the occurrence of gestational hypertension and pre-eclampsia.

AIMS: Hypertensive disorders of pregnancy (HDP) is a unique disease during gestational period, which is detrimental to pregnancy outcome. This study examined the clinical significance of long non-coding RNA GAS5 in gestational hypertension (GH) and preeclampsia (PE), aiming to explore potential biomarkers for the disease detection. METHODS: 180 pregnant women with HPD including 90 cases with GH and 90 cases with PE, and another 100 healthy pregnant women were enrolled. Serum GAS5 levels were measured by RT-qPCR method. The diagnostic performance of GAS5 was assessed in GH and PE through plotting receiver operating characteristic (ROC) curve. Logistic regression was applied for the identification of independent factors. RESULTS: Elevated serum GAS5 was identified in GH patients, and its diagnostic performance in discriminating GH cases from healthy people was determined by ROC curve. Serum GAS5 was positively associated with SBP, DBP, LDL-C and CRP values. Cases with PE had an increased serum GAS5 level relative to those with GH. Serum GAS5 was identified to be an independent predictor for PE, and can differentiate PE cases from GH ones. with a good diagnositc performance. Cases with high levels of serum GAS5 had a high risk of poor pregnancy outcomes. CONCLUSION: Elevated serum GAS5 could serve as an effective diagnostic biomarker in discriminating GH patients from healthy people by first trimester screening. Detection of serum GAS5 level has a certain predictive value for PE.

First-Trimester Serum Cytokine Profile in Pregnancies Conceived After Assisted Reproductive Technology (ART) With Subsequent Pregnancy-Induced Hypertension.

Pregnancy-induced hypertension (PIH) is one of the most common pregnancy complications that seriously affects the mother and fetus. The incidence of PIH is higher in pregnancies conceived after assisted reproductive technology (ART) than in spontaneous pregnancies; thus, exploring potential serum biomarkers before PIH onset is of great significance for effective early prediction and prevention of PIH in the ART population. Cytokines are involved in the inflammatory response and immune regulation, which play an essential role in the pathogenesis of PIH. A description of the cytokine profile in the first trimester of pregnancy could help identify new diagnostic tools and develop targeted therapies for PIH in the ART population. The concentrations of classical predictive markers for PIH and another 48 cytokines were measured in the first-trimester pregnancy serum samples from 33 PIH patients and 33 matched normotensive controls (NC), both of whom conceived after ART treatment. The measured values were compared and analyzed between NC and PIH, followed by comprehensive bioinformatic analysis and logistic regression analysis. There was no significant difference in classical predictive markers, including Activin A, PlGF, sFLT1 (VEGFR), and sFLT1/PlGF, between the PIH and NC groups (P > 0.05), while 29 cytokines were significantly lower in the PIH group than in the NC group (P < 0.05). Logistic regression analysis revealed that 17 cytokines (IL-2Rα, M-CSF, IL-6, IL-2, ß-NGF, IL-7, IL-12 (p70), SCF, IL-10, IL-9, MIG, GM-CSF, LIF, IL-1α, MCP-3, IL-4, and HGF) in the first-trimester pregnancy serum were significantly negatively correlated with the subsequent onset of PIH. With the top 3 cytokines (IL-7, MIG, and SCF) of receiver operating characteristic (ROC) analysis, we constructed an efficient multifactor combined detection and prediction model for PIH in ART pregnancy. Classical early predictors for hypertensive disorder complicating pregnancy cannot distinguish PIH from their normal peers in ART pregnancy. In comparison, the description of the cytokine profile in the first trimester of pregnancy enables us to distinguish high-risk ART pregnancy for PIH, permitting enough time for PIH prevention therapy. The cytokine profile we described also provides immunological insight into the further mechanistic exploration of PIH.

Expression and clinical significance of miR-204 in patients with hypertensive disorder complicating pregnancy.

OBJECTIVE: Hypertensive disorder complicating pregnancy (HDCP) is a unique and common obstetrical complication in pregnancy. The current study sought to investigate the diagnostic value of serum miR-204 in HDCP patients. METHODS: A total of 196 HDCP patients were enrolled, with 54 healthy pregnant women as controls. The expression levels of miR-204 and inflammatory factors in the serum were determined. Receiver operating characteristic (ROC) curve was used to assess the diagnostic value of miR-204 in HDCP patients. Person coefficient was introduced to analyze the correlation between miR-204 and inflammatory indexes. Kaplan-Meier method was employed to analyze the effect of miR-204 expression on the incidence of adverse pregnancy outcomes. Logistic regression was adopted to assess the risk factors for adverse pregnancy outcomes. RESULTS: miR-204 expression was upregulated in the serum of HDCP patients. The serum miR-204 level > 1.432 could assist the diagnosis of HDCP. miR-204 level in the serum was positively correlated with TNF-α, IL-6, and hs-CRP concentrations in HDCP patients. The risk of adverse outcomes was higher in pregnant women with high miR-204 expression. High miR-204 expression was associated with an increased risk of adverse pregnancy outcomes after adjusting the family history of HDCP, systolic pressure, diastolic pressure, AST, ALT, LDH, 24-h urinary protein, TNF-α, IL-6, and hs-CRP. CONCLUSION: The high expression of miR-204 assists the diagnosis of HDCP and is an independent risk factor for adverse pregnancy outcomes in HDCP patients.

Modified multiple marker aneuploidy screening as a primary screening test for preeclampsia.

BACKGROUND: Abnormal levels of maternal biochemical markers used in multiple marker aneuploidy screening have been associated with adverse pregnancy outcomes. This study aims to assess if a combination of maternal characteristics and biochemical markers in the first and second trimesters can be used to screen for preeclampsia (PE). The secondary aim was to assess this combination in identifying pregnancies at risk for gestational hypertension and preterm birth. METHODS: This case-control study used information on maternal characteristics and residual blood samples from pregnant women who have undergone multiple marker aneuploidy screening. The median multiple of the median (MoM) of first and second trimester biochemical markers in cases (women with PE, gestational hypertension and preterm birth) and controls were compared. Biochemical markers included pregnancy-associated plasma protein A (PAPP-A), placental growth factor (PlGF), human chorionic gonadotropin (hCG), alpha feto-protein (AFP), unconjugated estriol (uE3) and Inhibin A. Logistic regression analysis was used to estimate screening performance using different marker combinations. Screening performance was defined as detection rate (DR) and false positive rate (FPR). Preterm and early-onset preeclampsia PE were defined as women with PE who delivered at < 37 and < 34 weeks of gestation, respectively. RESULTS: There were 147 pregnancies with PE (81 term, 49 preterm and 17 early-onset), 295 with gestational hypertension, and 166 preterm birth. Compared to controls, PE cases had significantly lower median MoM of PAPP-A (0.77 vs 1.10, p < 0.0001), PlGF (0.76 vs 1.01, p < 0.0001) and free-ß hCG (0.81 vs. 0.98, p < 0.001) in the first trimester along with PAPP-A (0.82 vs 0.99, p < 0.01) and PlGF (0.75 vs 1.02, p < 0.0001) in the second trimester. The lowest first trimester PAPP-A, PlGF and free ß-hCG were seen in those with preterm and early-onset PE. At a 20% FPR, 67% of preterm and 76% of early-onset PE cases can be predicted using a combination of maternal characteristics with PAPP-A and PlGF in the first trimester. The corresponding DR was 58% for gestational hypertension and 36% for preterm birth cases. CONCLUSIONS: Maternal characteristics with first trimester PAPP-A and PlGF measured for aneuploidy screening provided reasonable accuracy in identifying women at risk of developing early onset PE, allowing triage of high-risk women for further investigation and risk-reducing therapy. This combination was less accurate in predicting women who have gestational hypertension or preterm birth.

Serum Levels of N-Terminal Pro-Brain Natriuretic Peptide in Gestational Hypertension, Mild Preeclampsia, and Severe Preeclampsia: A Study from a Center in Zhejiang Province, China.

BACKGROUND Pre-eclampsia is one of the primary causes of maternal and newborn mortality. The pathogenesis of pre-eclampsia is still unclear. We aimed to investigate the link between serum N-terminal pro-brain natriuretic peptide (NT-proBNP) levels and pre-eclampsia. MATERIAL AND METHODS A total of 102 pregnant women with hypertensive disorders of pregnancy who were hospitalized and delivered in Wenzhou People's Hospital from January 2019 to December 2019 were selected, including 43 patients with gestational hypertension, 32 patients with mild pre-eclampsia, and 27 patients with severe pre-eclampsia. Enzyme-linked fluorescence analysis was used to detect the serum NT-proBNP levels of the patients before delivery. We used the t test and ANOVA to compare differences between groups. Receiver operating curve (ROC) and the Youden index were used to evaluate the detection efficiency. RESULTS The average level of serum NT-proBNP in patients with mild pre-eclampsia was 197.12±105.80 pg/mL, which was significantly higher than that of patients with gestational hypertension (48.98±32.45 pg/mL) (P<0.05). Serum NT-proBNP in patients with severe pre-eclampsia (851.04±879.85 pg/mL) was higher than that in patients with moderate pre-eclampsia (P<0.05). The area under the ROC curve for diagnosing pre-eclampsia using NT-proBNP was 0.973, with NT-proBNP of 129.5 pg/mL as the cut-off value. The Youden index was 0.824, with a sensitivity for predicting pre-eclampsia of 84.7% and a specificity of 97.7%. CONCLUSIONS The level of serum NT-proBNP was as an effective indicator for predicting pre-eclampsia and judging the risk of pre-eclampsia.

Higher hemoglobin levels are an independent risk factor for gestational diabetes.

Incidence of gestational diabetes (GDM) has increased rapidly. It poses significant risks for both mother and fetus affecting also negatively their longer-term metabolic heath. We asked whether early pregnancy maternal hemoglobin (Hb) levels, indicative for tissue oxygenation, would affect mother's metabolic health and fetal outcome. We assessed in FinnGeDi, a Finnish multicenter case-control study for GDM (n = 1828), association of maternal 1st trimester Hb levels with metabolic parameters and perinatal outcome. Our data show that mothers with GDM had higher Hb levels compared to controls (mean difference 1.746 g/L). Hb levels associated positively with pre-pregnancy body mass index (BMI), fasting glucose levels and glucose levels in a glucose tolerance test and systolic and diastolic blood pressure (bp) levels. When assessed in quartiles the highest Hb quartile had more chronic and gestational hypertension and the most adverse outcome of the metabolic parameters, dose-dependency seen in bp, BMI and glucose levels. In a multivariable regression analysis Hb levels remained an independently associated parameter for GDM after adjusting for key covariates (OR 1.019, 95% CI [1.007; 1.031]). In conclusion, higher maternal Hb levels within the normal variation are an independent risk factor for GDM in this population but have little effect on perinatal outcome.

sFlt-1/PlGF ratio in hypertensive disorders of pregnancy in patients affected by COVID-19.

OBJECTIVES: To analyze soluble Fms-like tyrosine Kinase 1 (sFlt-1) and Placental Growth Factor (PlGF) ratio concentrations in COVID-19 pregnant patients with and without Hypertensive Disorders of Pregnancy (HDP), compared with non COVID-19 pregnant patients with HDP and a control group. STUDY DESIGN: We recruited and obtained a complete follow-up of 19 COVID-19 pregnant patients with HDP and of 24 COVID-19 normotensive pregnant patients. Demographic, clinical and sFlt-1/PlGF ratio findings were compared with a group of 185 non COVID-19 pregnant patients with HDP and 41 non COVID normotensive patients. Findings were based on univariate analysis and on a multivariate adjusted model, and a case by case analysis of COVID-19 pregnant patients with an abnormal sFlt-1/PlGF ratio > 38 at recruitment. MAIN OUTCOME MEASURES: sFlt-1/PlGF ratio. RESULTS: We confirmed a significant higher prevalence of HDP in women affected by COVID-19 compared to control population. sFlt-1/PlGF ratio was found high in HDP patients, with and without of Sars-Cov2 infection. COVID-19 patients with worse evolution of the disease showed greater rates of obesity and other comorbidities. sFlt/PlGF ratio proved not to be helpful in the differential diagnosis of the severity of this infection. CONCLUSIONS: COVID-19 pregnant patients showed a higher prevalence of HDP compared to non COVID-19 controls, as well as higher comorbidity rates. In spite of the possible common endothelial target and damage, between Sars-Cov-2 infection and HDP, the sFlt1/PlGF ratio did not correlate with the severity of this syndrome.

A wide range of triglyceride levels is sufficient for fetal growth at gestational weeks 12-16, but higher triglyceride levels are associated with gestational hypertension.

OBJECTIVES: To learn whether and how lipid levels are associated with gestational hypertension and fetal growth in normal pregnancy. STUDY DESIGN: In a case-control study course, 464 patients with gestational hypertension were pooled into a case group; a total of 1077 women with full-term pregnancies and no pregnancy complications were selected as controls. In a cross-sectional study, whether maternal lipid levels were associated with fetal growth were evaluated in 1077 healthy controls. MAIN OUTCOME MEASURES: Maternal lipids and glucose levels and fetal measurements. RESULTS: Maternal levels of triglyceride (TG) were significantly higher in the case group than in controls at gestational weeks 12-16. Levels of TG, total cholesterol (TC) and low-densitylipoprotein (LDL-C) in control mothers increased gradually and significantly with increasing gestational week, however, these lipid concentrations lost these steady elevating trends with gestational week increases in the cases. Binary logistic regression showed that TG is a risk factor associated with hypertension at gestational weeks 12-16 and independent to maternal blood levels of LDL-C and glucose. Of the healthy mothers at gestational weeks 12-16, quantile regression showed that TG levels were not associated with real-time fetal growth measurements or final birthweight. The reference standards for maternal TG levels were estimated via the 10th, 25th, 50th, 75th, and 90th percentiles by gestational week. CONCLUSIONS: Maternal TG levels are associated with gestational hypertension, and a wide range of TG levels is sufficient for fetal growth within a given gestational week.

HSPA8 Is Identified as a Novel Regulator of Hypertensive Disorders in Pregnancy by Modulating the ß-Arrestin1/A1AR Axis.

Heat shock protein alpha 8 (HSPA8) was found to be downregulated in the placentas of patients with hypertensive disorders in pregnancy (HDP). We aim to explore the underlying role and mechanism of HSPA8 in HDP progression. Herein, HSPA8 mRNA expression in placentas and peripheral blood of patients with HDP and normal pregnant controls was measured with RT-qPCR. We found that HSPA8 expression was downregulated in placentas and peripheral blood of patients with HDP. HTR8/SVneo human trophoblast cells were transfected with pcDNA-HSPA8 or si-HSPA8. HSPA8 overexpression promoted cell proliferation, migration, and MMP-2 and MMP-9 protein levels, and inhibited apoptosis, while HSPA8 silencing showed the opposite results. Co-immunoprecipitation assay validated the binding between HSPA8 and ß-arrestin1, as well as ß-arrestin1 and A1AR proteins. HSPA8 bound with ß-arrestin1 protein and promoted ß-arrestin1 expression. ß-arrestin1 bound with A1AR protein and inhibited A1AR expression. Then, HTR8/SVneo cells were transfected with pcDNA-HSPA8 alone or together with si-ß-arrestin1, as well as transfected with pcDNA-ß-arrestin1 alone or together with pcDNA-A1AR. ß-arrestin1 silencing reversed the effects of HSPA8 overexpression on HTR8/SVneo cell functions. ß-arrestin1 overexpression promoted cell proliferation migration, and MMP-2 and MMP-9 protein levels, and inhibited apoptosis, while these effects were reversed by A1AR overexpression. Lentivirus HSPA8 overexpression vector (Lv-HSPA8) was injected into a preeclampsia (PE) rat model, which attenuated blood pressure and fetal detrimental changes in PE rats. In conclusion, HSPA8 promoted proliferation and migration and inhibited apoptosis in trophoblast cells, and attenuated the symptoms of PE rats by modulating the ß-arrestin1/A1AR axis. Our study provided a novel theoretical evidence and potential strategy for HDP treatment.

Serum Expression of ESM-1, HMWA, and AGEs and Its Relationship with Disease Severity in Patients with Gestational Hypertension.

OBJECTIVE: The research is to investigate the expression and the relationship between serum endothelial cell-specific molecular molecule-1 (ESM-1), high molecular weight adiponectin (HMWA), and late glycosylation terminal product (AGEs) in patients with gestational hypertension. METHODS: 75 patients with pregnant hypertension who were treated in our hospital from June 2019 to June 2020 were selected as the case group, and 70 healthy pregnant women with pregnancy examination at the same period in our hospital were selected as the control group to analyze the changes in serum ESM-1, HMWA, and AGEs levels and the correlation with the degree of illness and their predictive value. RESULTS: Serum ESM-1 and AGEs were significantly higher in the case group than in the control group. Serum HMWA was significantly lower than that in the control group (P < 0.05). The gestational hypertensive serum ESM-1 and AGEs was significantly lower than in patients with mild preeclampsia and severe preeclampsia. Serum HMWA was significantly higher than in patients with mild preeclampsia and severe preeclampsia. Serum ESM-1 and AGEs of mild preeclampsia were significantly lower than in patients with severe preeclampsia. Serum HMWA was significantly higher than in patients with severe preeclampsia (P < 0.05). The result of correlation analysis shows a positive correlation between serum ESM-1 and AGEs (P < 0.05). A negative correlation was observed between HMWA and the degree of illness (P < 0.05). CONCLUSION: Serum ESM-1, HMWA, and AGEs are abnormally expressed in gestational hypertension, are closely related to the degree of condition, and have important clinical significance for condition control.