Preeclampsia In Women Research Articles

Symposium 2-3 - Thrombomodulin as a new therapeutic target for preeclampsia

Thrombomodulin (TM) is a transmembrane glycoprotein abundantly expressed on vascular endothelial cells and have been known as molecules with anticoagulant and anti-inflammatory properties. TM binds to a danger signal, HMGB1, and suppresses the inflammatory response induced by HMGB1. This study aimed to clarify the relationship between HMGB1 and the pathological mechanisms of preeclampsia (PE). Additionally, we explored the therapeutic potential of TM for PE. We used angiotensin II (AngII)-induced PE mouse model, in which continuous administration of Ang II using subcutaneous pump developed PE symptoms in pregnant mice. AngII administration caused placental release of HMGB1, leading to enhanced production of sFlt-1 and the inflammatory cytokines in trophoblast cells. When TM was given to the PE mouse model, improvements in fetal growth, maternal hypertension and urinary protein were observed. Furthermore, in-vitro experiments suggest that antagonism of HMGB1 underlies the therapeutic effect of TM on PE. In the studies using the serum samples and placental tissues obtained from pregnant women, HMGB1 and TM levels in peripheral blood were higher in pregnant women with PE, and there was a negative correlation between the two in pregnant women with PE. Immunostaining of PE placentas showed HMGB1 release from the nucleus and defective staining of membrane-type TM on the surface of syncytiotrophoblast. These findings supported that the increased HMGB1 and TM levels in the peripheral blood of PE women originated from the placenta. In conclusion, HMGB1 released from the dysfunctional placenta is deeply involved in the pathogenesis of PE and that inhibition of HMGB1 action by TM leads to improvement of placental function. Treatment strategy aiming to inhibit HMGB1 action, including TM, is a new therapeutic approach for PE.

Evaluation of CD39, CD73, HIF-1α, and their related miRNAs expression in decidua of preeclampsia cases compared to healthy pregnant women.

The Preeclampsia (PE) molecular mechanisms are not fully revealed and different biological processes are involved in the pathogenesis of PE. We aimed to evaluate adenosine and hypoxia-related signaling molecules in PE patients in the current study. Decidua tissue and peripheral blood samples were taken from 25 healthy pregnant and 25 PE women at delivery time. CD39, CD73, and Hypoxia-inducible factor-alpha (HIF-α) were evaluated in mRNA and protein level using real-time PCR and western blotting techniques, respectively. Also, miR-30a, miR-206, and miR-18a expression were evaluated by real-time PCR. At last, secretion levels of IGF and TGF-β in the taken serum of blood samples were measured by ELISA. Our results revealed that Expression of CD39 is decreased in PE cases versus healthy controls at mRNA and protein levels (p = 0.0003 for both). CD73 and HIF-α showed an increased level of expression in PE patients at RNA and protein status (p = 0.0157 and p < 0.0001 for protein evaluation of CD73 and HIF-α, respectively). The miRNA-30a (p = 0.0037) and miR-206 (p = 0.0113) showed elevated expression in the decidua of the PE group. The concentration of secreted IGF-1 (p = 0.0002) and TGF-β (p = 0.0101) in serum samples of PE cases compared to the healthy group were decreased. In conclusion, our results showed that aberrant expression of molecules that are involved in ATP catabolism and the hypoxic conditions is observed in PE cases and involved in their hypertension and inflammation could be served as PE prognosis by more confirming in comprehensive future studies. miR-206 and miR-30a play a role by regulating CD39 and CD73 as molecules that are involved in ATP catabolism as well as regulating the production of IGF-1 in the process of hypertension, which is the main feature in patients with preeclampsia. On the other hand, decreased level of miR-18a lead to upregulation of HIF-1a, and the consequence condition of hypoxia increases hypertension and inflammation in these patients.

Mediators of inflammation resolution and vasoactive eicosanoids in gestational diabetes and preeclampsia.

Women with gestational diabetes (GDM) have an increased risk of preeclampsia and postpartum diabetes. Inflammation associates with both GDM and preeclampsia. This study examined specialized proresolving mediators (SPM) that direct inflammation resolution and eicosanoids that are involved in inflammation, in relation to the development of preeclampsia and ongoing postpartum glucose intolerance in GDM. Participants were selected from a prospective study examining the development of preeclampsia in women with GDM. Four groups of age-matched women were studied: GDM ( n = 20), GDM who developed preeclampsia (GDM+PE, n = 21), GDM who remained glucose-intolerant postpartum (GDM+PPIGT, n = 20), or pregnancies with glucose tolerance within the normal range (NGT, n = 21). Measurement of SPM (E-series resolvins and D-series resolvins), SPM pathway intermediates (14-HDHA, 18-HEPE and 17-HDHA), 20-hydroxyeicosatetraenoic acid (20-HETE), and the urinary metabolite of the vasodilator prostacyclin 2,3-dinor-6-Keto-PGF 1α , were made at 28, 32 and 36 weeks gestation and at 6 months postpartum. Compared with GDM, GDM+PE had elevated levels of 20-HETE and the SPM pathway intermediates 14-HDHA, 18-HEPE, 17-HDHA, at 32 weeks, and the SPM RvE1 at 32 and 36 weeks gestation. Compared with NGT and regardless of whether they developed preeclampsia or PPIGT, GDM had lower levels of 2,3-dinor-6-Keto-PGF 1α during pregnancy. Reduced levels of the prostacyclin metabolite 2,3-dinor-6-Keto-PGF 1α may contribute to the increased risk of preeclampsia in women with GDM. The increase in 20-HETE, a vasoconstrictor and mediator of inflammation, and SPM that contribute to inflammation resolution, prior to the onset of preeclampsia require further investigation to clarify their clinical significance.

Relationship of serum lipid profiles in preeclampsia and normal pregnancy, Bangladesh.

The purpose of this present study to investigate the lipid profile levels and basal body mass index in preeclampsia and normal pregnancy in Bangladeshi women. This case-control study was conducted at Sheba Hospital Kaligonj Bangladesh with 70 participants among 35 normal pregnancy (control) and 35 preeclampsia women (case) were enrolled from August 2018 to July 2019. Blood samples were obtained for analysis of total cholesterol, triglyceride and high-density lipoprotein by enzymatic assays and low-density lipoprotein by using Fried Ewald's formula in between 22-36 weeks of gestation. This study found the mean age of preeclampsia and normal pregnancy women were 24.71±2.56 and 23.09±2.1 respectively with significant (P= 0.005). Basal body mass index, total cholesterol, triglyceride and low-density lipoprotein significantly higher (P=0.002), (P= 0.000), (P= 0.022) and (P=0.000) in preeclampsia compared to normal pregnancy respectively. While high-density lipoprotein comparatively lower in preeclampsia than normal pregnancy and consider significant as (P=0.037). Abnormal lipid profile and increased body mass index is contributed to the development of preeclampsia. The frequent antenatal monitoring of lipid profiles provides the status which helps to require management and reduces the preeclampsia which enhances maternal and fetal wellbeing and fetal outcome.

Expression of Concern: First versus second trimester mean platelet volume and uric acid for prediction of preeclampsia in women at moderate and low risk

Expression of Concern: First versus second trimester mean platelet volume and uric acid for prediction of preeclampsia in women at moderate and low risk

Increased Risk of Preeclampsia in Women With a Genetic Predisposition to Elevated Blood Pressure.

Background:Preeclampsia causes significant maternal and perinatal morbidity. Genetic factors seem to affect the onset of the disease. We aimed to investigate whether the polygenic risk score for blood pressure (BP; BP-PRS) is associated with preeclampsia, its subtypes, and BP values during pregnancy.Methods:The analyses were performed in the FINNPEC study (Finnish Genetics of Pre-Eclampsia Consortium) cohort of 1514 preeclamptic and 983 control women. In a case-control setting, the data were divided into percentiles to compare women with high BP-PRS (HBP-PRS; >95th percentile) or low BP-PRS (≤5th percentile) to others. Furthermore, to evaluate the effect of BP-PRS on BP, we studied 3 cohorts: women with preeclampsia, hypertensive controls, and normotensive controls.Results:BP values were higher in women with HBP-PRS throughout the pregnancy. Preeclampsia was more common in women with HBP-PRS compared with others (71.8% and 60.1%, respectively; P=0.009), and women with low BP-PRS presented with preeclampsia less frequently than others (44.8% and 61.5%, respectively; P<0.001). HBP-PRS was associated with an increased risk for preeclampsia (odds ratio, 1.7 [95% CI, 1.1–2.5]). Furthermore, women with HBP-PRS presented with recurrent preeclampsia and preeclampsia with severe features more often.Conclusions:Our results suggest that HBP-PRS is associated with an increased risk of preeclampsia, recurrent preeclampsia, and preeclampsia with severe features. Furthermore, women with HBP-PRS present higher BP values during pregnancy. The results strengthen the evidence pointing toward the role of genetic variants associated with BP regulation in the etiology of preeclampsia, especially its more severe forms.

Association of placental fatty acid desaturase 2 (FADS2) methylation with maternal fatty acid levels in women with preeclampsia

IntroductionBiosynthesis of long-chain polyunsaturated fatty acids requires sequential activities of desaturases and elongases for conversion of fatty acid precursors to products. The delta-6 desaturase enzyme, encoded by FADS2 gene, is a rate limiting enzyme in this pathway. Alterations in D6D enzyme activity can lead to altered fatty acid profiles. ObjectivesTo examine differences in placental DNA methylation (DNAm) and expression of FADS2 gene in preeclampsia women compared to normal women and their association with maternal variables (plasma fatty acids, desaturase enzyme index, blood pressure), placental weight and birth outcomes. MethodsDNAm and expression of FADS2 gene were examined in placentae of normotensive (n = 100) control and preeclampsia (n = 100) women using pyrosequencing and quantitative real-time PCR respectively. Women with preeclampsia included those delivering at term (n = 43, gestation ≥ 37 weeks; T-PE) or preterm (n = 57, gestation < 37 weeks; PT-PE). A total of 26 CpGs in FADS2 promoter and region around it, were analysed in two PCR reactions (region 1 and 2). ResultsOut of 13 CpGs in region 1, significant hypermethylation was noted at CpG3 in T-PE (p = 0.03) and of 13 CpGs in region 2, CpG2 (p = 0.008), CpG11 (p = 0.04), CpG12 (p = 0.001) were hypomethylated and CpG13 (p = 0.001) was hypermethylated in preeclampsia group, as compared to controls. FADS2 expression was lower in PT-PE as compared to controls (p = 0.04). DNAm at various CpGs in the FADS2 were associated with maternal plasma FADS2 enzyme index and also associated with maternal fatty acid levels. However, we did not observe any association of DNAm with maternal blood pressure, placental weight and birth outcomes. ConclusionsThis study for the first time reports differential methylation of FADS2 and its association with impaired maternal fatty acid metabolism in preeclampsia and provides a mechanistic basis to our earlier observations of altered maternal LCPUFA levels in women with preeclampsia.

Protein S and protein C in preeclamptic pregnant women

Background and purpose: Deficits of protein C and protein S are associated with an increased incidence of thrombotic disorders. The aim of the present study was to determine the levels of the mentioned natural coagulation inhibitors in women with preeclampsia and in a 6-months followup period after delivery.Materials and methods: This case-control clinical study included 55 pregnant women (cases) with preeclampsia and 50 healthy normotensive pregnant women (controls) in tertiary perinatal centre. Protein C levels were determined photometrically using a chromogen substrate, and protein S levels were determined using the clot method and optic detection.Results: There were no significant differences in protein C and protein S levels between women with preeclampsia and healthy pregnant women; however, six months after delivery protein S levels were significantly lower in women with preeclampsia as compared to healthy peers, whereas protein C levels did not differ significantly.Conclusion: Possible long-term cardiovascular morbidity should be assessed in preeclampsia women.

Home Blood Pressure for the Prediction of Preeclampsia in Women With Preexisting Diabetes.

Outside of pregnancy, home blood pressure (BP) has been shown to be superior to office BP for predicting cardiovascular outcomes. This work aimed to evaluate home BP as a predictor of preeclampsia in comparison with office BP in pregnant women with preexisting diabetes. A prospective cohort study was conducted of 404 pregnant women with preexisting diabetes; home BP and office BP were measured in early (9 weeks) and late pregnancy (35 weeks). Discriminative performance of home BP and office BP for prediction of preeclampsia was assessed by area under the receiver operating characteristic curves (AUC). In total 12% (n = 49/404) developed preeclampsia. Both home BP and office BP in early pregnancy were positively associated with the development of preeclampsia (adjusted odds ratio (95% CI) per 5 mm Hg, systolic/diastolic): home BP 1.43 (1.21-1.70)/1.74 (1.34-2.25) and office BP 1.22 (1.06-1.40)/1.52 (1.23-1.87). The discriminative performance for prediction of preeclampsia was similar for early-pregnancy home BP and office BP (systolic, AUC 69.3 [61.3-77.2] vs 64.1 [55.5-72.8]; P = .21 and diastolic, AUC 68.6 [60.2-77.0] vs 66.6 [58.2-75.1]; P = .64). Similar results were seen when comparing AUCs in late pregnancy (n = 304). In early and late pregnancy home BP was lower than office BP (early pregnancy P < .0001 and late pregnancy P < .01 for both systolic and diastolic BP), and the difference was greater with increasing office BP. In women with preexisting diabetes, home BP and office BP were positively associated with the development of preeclampsia, and for the prediction of preeclampsia home BP and office BP were comparable.

Immediate weight loss before ovarian stimulation with intrauterine insemination is associated with a lower risk of preeclampsia in women with obesity and unexplained infertility

ObjectiveTo determine whether successful weight loss before ovarian stimulation with intrauterine insemination (OS-IUI) affects the risk of future pregnancy complications among women with obesity and unexplained infertility after fertility treatment.DesignSecondary analysis of the randomized controlled clinical trial Improving Reproductive Fitness Through Pretreatment With Lifestyle Modification in Obese Women With Unexplained Infertility (FIT-PLESE).SettingMultiple academic health centers in the United States.Patient(s)Three hundred seventy-nine women with obesity and unexplained infertility who underwent standard infertility treatment after a lifestyle intervention.Intervention(s)The FIT-PLESE trial evaluated whether prepregnancy lifestyle interventions (diet with weight loss medication and exercise vs. exercise alone) before OS-IUI improved the live birth rate among women with obesity and unexplained infertility. Although the primary outcome of FIT-PLESE was live birth rate, we compared the demographics and subsequent pregnancy complications of women who successfully lost some weight with those of women who did not lose any during the interventions.Main Outcome Measure(s)Obstetric complications by groups were compared using χ2 and Fisher’s exact tests, and continuous variables were compared using Student’s t-tests. Logistic regression was used to assess the odds of preeclampsia after adjustment for the randomized treatment arm in FIT-PLESE.Result(s)There was a nonsignificant trend toward a lower risk of intrauterine growth restriction (4% vs. 16%, P = .124) and preterm delivery (6% vs. 15%, P = .343) among patients who lost at least some weight. The risk of preeclampsia was significantly lower (6% vs.35%, P = .002) in the weight loss group (odds ratio, 0.09; 95% confidence interval, 0.016–0.505; P = .006) after adjustment for treatment assignment.Conclusion(s)Among women with obesity and unexplained infertility who had live births after fertility treatment, prepregnancy weight loss due to lifestyle interventions before OS-IUI was associated with a lower risk of preeclampsia.

Excessive Immune Activation and the Correlation with Decreased Expression of PD-1 at the Maternal-Fetal Interface in Preeclampsia.

The etiology of preeclampsia (PE) is still unknown, and excessive immune activation is an important component of its pathogenesis. Programmed cell death protein 1 (PD-1) is one of immune checkpoints which may prevent overactivated immune attack and lead to a tolerant immune microenvironment. Little is known about the involvement of PD-1-mediated immunoregulation at the maternal-fetal interface in PE. To investigate the inflammatory pattern and the involvement of PD-1 in the decidua of women with PE, decidual tissues were obtained from PE and control pregnant women. Quantitative RT-PCR analysis of the mRNA levels of the inflammatory cytokines was performed. PD-1 expression was detected by immunohistochemistry, western blot analysis, and flow cytometry. To prove the role of PD-1, decidual immune cells were incubated with blocking antibodies, and the inflammatory cytokines were detected by ELISA. We observed that the mRNA levels of IL-1β, IL-6, TNF-α, and IFN-γ were higher in the decidua of the PE group than in the decidua of the control group. The mRNA levels of IL-4 and IL-10 were lower in PE. The expression level of PD-1 was significantly downregulated, and the proportion (%) of PD-1 + CD45 + cells was significantly lower in PE. There was a significant linear correlation between PD-1 expression and common proinflammatory cytokines in the decidua. Anti-PD-1 blocking antibody significantly increased the secretion of proinflammatory cytokines. Our data suggested that the inflammatory pattern and decreased PD-1 expression in the decidua might play an active role in the local immunoregulatory mechanisms of PE. The PD-1 pathway in the maternal-fetal interface possibly function to break the tolerant immune microenvironment in PE via inflammatory cytokines.

AQUAPORIN-3 AND HEPARANASE GENETIC POLYMORPHISMS MAY MODULATE ANGIOGENESIS INFLUENCING THE RISK OF HYPERTENSIVE DISORDERS IN WOMEN

Objective: Preeclampsia (PE), a pregnancy complication triggered by oxidative stress and hypoxia, compromises mother and baby health and changes mother’s blood vessels increasing the risk for hypertension(HT). Aquaporin-3 (AQP3) is a water/H2O2/glycerol channel with implications in redox signaling. Heparanase (HPSE) has a role in extracellular matrix remodeling during angiogenesis. So far, no relation between AQP3 and HPSE genetic polymorphisms in PE subjects has been addressed. Thus, we aimed to investigate the association of AQP3(rs2231231) and HPSE(rs4693608) polymorphisms with the development of hypertensive disorders in women. Design and method: We investigated the distribution of AQP3 and HPSE genetic variations in a cohort of 150 normotensive (NT) or PE women, along with intermediate phenotype and anthropometric parameters. In a prospective study, women were reclassified 2–16 years after being PE or NT during pregnancy as NT or HT and genetic associations were reevaluated. Data was analyzed using SPSS software, P-values &lt; 0.05 were statistically significant. Results: No differences were found in the distribution of the studied polymorphisms in PE. Allele A of AQP3 was more prevalent in HT after pregnancy(P = 0.014) and correlated with subjects with increased systolic(P = 0.017) and diastolic(P = 0.008) blood pressures. Moreover, allele A was considered the allele of risk, associated with a 3.53-fold higher risk(P = 0.018) to develop HT after pregnancy. In this cohort, serum myeloperoxidase (MPO) higher levels correlated with PE (P = 0.000) and HT (P = 0.024) and were associated with HT after a NT pregnancy(P = 0.000). Although HPSE did not correlate with PE or HT, Allele A carriers were associated with increased Apolipoprotein A(ApoA;P = 0.027), uric acid(P = 0.027) and MPO(P = 0.005) in PE. In HPSE, PE subjects with allele G correlated with increased number of leucocytes(P = 0.048) while the presence of allele A was associated with decreased serum uric acid(P = 0.028). When the 4 groups were reevaluated, allele A of HPSE was associated with decreased blood glucose levels(P = 0.05) and increased pulse pressure(P = 0.003) and uric acid(P = 0.05) in women that had PE. Allele G was more frequent with lower levels of leucocytes(P = 0.024) in women that had PE and later HT. Conclusions: The AQP3 polymorphism is a promising biomarker for HT. HPSE polymorphism predicts PE-associated variations in the intermediate phenotype.

No association in maternal serum levels of TMAO and its precursors in pre-eclampsia and in non-complicated pregnancies.

Only a few studies have explored the role of microbiota-dependent metabolite trimethylamine N-oxide (TMAO) in non-complicated pregnancy and in pre-eclampsia (PE). We enrolled 139 PE and 29 healthy pregnant women in a nested case control study. We hypothesized that elevated levels of circulating TMAO and its precursors choline and glycine betaine in the late second or in third trimester might contribute to the PE and are associated with the onset of the disease and clinical features such as elevated blood pressure. The association with a few available lifestyle factors (use of fish and physical activity) was also evaluated. In contrast with the previous findings, there was no difference in TMAO concentration between PE and healthy women. In addition, TMAO concentration was not associated with any of the PE related clinical features, angiogenic or inflammatory markers. In future, it is crucial to obtain longitudinal data on TMAO in both non-complicated and in PE pregnancies before we could have more detailed understanding of TMAO.

SERUM IRON, COPPER and ZINC LEVELS IN PREECLAMPSIA AND NORMOTENSIVE PRIMIGRAVIDA FEMALES

Hypertensive ailments of pregnancy are major health problems for women and their babies around the world. Among the hypertensive disorders, preeclampsia and eclampsia are the major risk factors for maternal and neonatal morbidity and mortality. Now preeclampsia is considered a state of oxidative stress, in which over utilization of antioxidants may proceed into worst form of this disease. So, this study was planned to assess the role of serum iron, copper and zinc as co factors for antioxidant system, and compare their levels within primigravida normotensive pregnant women and preeclampsia women. Methods: It was a cross-sectional comparative study conducted in Biochemistry department, University of health Sciences, Lahore. The study was carried out on 90 women which were divided into two equal groups of 45 each, preeclampsia and controls respectively. Serum levels of iron, copper and zinc were estimated by atomic absorption spectrometer. Data analyses were performed by utilizing SPSS version 20.0. Results: Serum levels of Fe and Cu were raised in preeclampsia patients, 151.85±61.22 (μg/dl), 130.83±48.29 (μg/dl) and serum Zn levels were decreased 77.94±23.55 (μg/dl) when compared with normotensive controls 104.39±55.36 (μg/dl), 116.64±26.56 (μg/dl), and 92.77±22.91 (μg/dl) respectively. A positive correlation between copper and systolic blood pressure (r= 0.440), BMI and weight (r = 0.543), while negative correlation of iron with zinc (r = -0.285) was observed in preeclamptic women. A negative correlation between copper and zinc (r = -0.440) was also observed in normal pregnant women but no such correlation was observed within Preeclampsia group. Conclusion: It is apparent from this study that increased levels of iron and copper and decreased levels of zinc during pregnancy is associated with the pathogenesis of preeclampsia.

Hubungan Derajat Preeklampsia terhadap Kadar Ldh di RSUD Abdul Moeloek Provinsi Lampung Periode Januari-Desember 2018

In preeclampsia, there is a proof that endothelial cells and changes in endothelial cell function hold an important role in the pathogenesis of preeclampsia. LDH serum is an important part of the evaluation of tissue damage associated with endothelial damage. Endothelial dysfunction contributes to inappropriate vasoconstriction and platelet aggregation which is an early sign of hypertension. LDH serum was found to be increased in mild and severe preeclampsia women compared to normal pregnant women in the third trimester but LDH serum values were significantly increased in women with severe preeclampsia. This study was aimed to find the relation between LDH levels and the degree of preeclampsia in RSUD Dr. H. Abdul Moeloek Lampung Province. This study used the data that is collected from medical records of patients with mild preeclampsia and severe preeclampsia who were treated in RSUD Dr. H. Abdul Moeloek on January to December, 2018. The sampling method used was Simple Random Sampling. The results showed that the average LDH level in pregnant women who had mild preeclampsia was 518.88 IU / L, whereas in pregnant women who had severe preeclampsia was 695.02 IU / L. The relation of the degree of preeclampsia to LDH levels using Mann-Withney test with the p value obtained was 0.032, which means p &lt;0.05.

Performance of sFlt-1/PIGF Ratio for the Prediction of Perinatal Outcome in Obese Pre-Eclamptic Women.

Obese women are at high risk of developing pre-eclampsia (PE). As an altered angiogenic profile is characteristic for PE, measurement of soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PIGF) ratio in the maternal serum can be helpful for PE diagnosis, as well as for adverse perinatal outcome (APO) prediction. There is growing evidence that obesity might influence the level of sFlt-1/PIGF and, therefore, the aim of the study was the evaluation of sFlt-1/PIGF as an APO predictor in obese women with PE. Pre-eclamptic women who had an sFlt-1/PIGF measurement at the time of diagnosis were retrospectively included. Women were classified according to their pre-pregnancy body mass index (BMI) as normal weight (BMI < 25 kg/m2), overweight (BMI > 25–29.9 kg/m2) or obese (BMI ≥ 30 kg/m2). APO was defined as the occurrence of one of the following outcomes: Small for gestational age, defined as a birthweight < 3rd centile, neonatal mortality, neonatal seizures, admission to neonatal unit required (NICU) or respiratory support. A total of 141 women were included. Of them, 28 (20%) patients were obese. ROC (receiver operating characteristic) analysis revealed a high predictive value for sFlt-1/PIGF and APO across the whole study cohort (AUC = 0.880, 95% CI: 0.826–0.936; p < 0.001). However, the subgroup of obese women showed a significantly lower level of sFlt-1 and, therefore, the performance of sFlt-1/PIGF as APO predictor was poorer compared to normal or overweight PE women (AUC = 0.754, 95% CI: 0.552–0.956, p = 0.025). In contrast to normal or overweight women, a ratio of sFlt-1/PIGF < 38 could not rule out APO in women with obesity.

Evaluation of Platelet Parameters in Patients with Preeclampsia in Comparison with Healthy Pregnant Women Referring to Ganjavian Hospital in Dezful City in 2019

Background: Preeclampsia is one of the complications of pregnancy that endangers the life of the mother and the fetus. This complication accounts for 18% of maternal mortality and is the second leading cause of maternal mortality in Iran. Various studies have shown the important role of platelets in the pathogenesis of preeclampsia. Objectives: This study was conducted to evaluate platelet parameters in patients with preeclampsia compared to healthy pregnant women who were referred to Ganjavian hospital in Dezful city in 2019. Methods: In this study, which is a retrospective case-control study, the files of women who gave birth in Ganjavian hospital in 2019 were examined. The files of the case group, which included people with preeclampsia, were selected as available samples (104 people), and the control group, which included pregnant women without preeclampsia, were randomly selected using a table of random numbers (104 cases). Criteria for entering the study in the group with preeclampsia included BP ≥ 140/90 mmHg, proteinuria of more than 300 mg in 24-hour urine or 30 mg consistently in random urine samples, and gestational age over 20 weeks. Also, people with any underlying disease, such as diabetes, chronic hypertension, known platelet disorders, multiple birth, and drug use (heparin, aspirin) in the group with preeclampsia were excluded from the study. The data of this study were analyzed using SPSS software version 20, and independent t-test, and Mann-Whitney U test at a significant level lower than 0.05. Results: There was no statistically significant difference in demographic factors between the two case and control groups. There was a statistically significant difference between the mean hemoglobin in healthy women 11.91 ± 1.30 and preeclampsia 10.89 ± 1.09 (P &lt; 0.0001). Also, according to the findings, the individuals of the two groups had a significant difference in terms of mean platelet volume (MPV): Healthy women: 10.79 ± 1.24 and preeclampsia women: 12.98 ± 1.16 (P &lt; 0.0001). Also, the results of the Mann-Whitney U test showed that there was a statistically significant difference between the number of platelets in healthy women (284.52 ± 60.58 mm3) and preeclampsia women (149.30 ± 30.38 mm3) (P &lt; 0.0001). Conclusions: Considering the importance of reducing the complications and mortality of pregnant mothers, early detection of changes in platelet factors during pregnancy can be a predictive factor in identifying people at risk for preeclampsia.

Histomorphometric study of placental blood vessels of chorion and chorionic villi vascular area among women with preeclampsia

IntroductionThe direction of blood movement in normal and abnormal placenta is curious from a morphometric point of view. Once pregnancy is compromised by an illness like hypertension, maternal and foetal distress can lead to negative outcomes. The quantitative variations in the blood vessels within the chorion and the chorionic villi in placentas from pregnancies are complicated by preeclampsia (PE) and are poorly defined. The purpose of this study was to calculate and explore the morphometric measurement of blood vessels involved in the progress of hypertension through pregnancy within the chorion and the chorionic villi among normotensive women (n = 39) versus a preeclamptic group (n = 35). MethodsMeasurements used a computerized morphometry system and a Vascular Medicine Institute (VMI) calculator. ResultsOur data showed a significant decrease in vessel area (VA), wall area (WA), lumen area (LA), mean wall thickness-boundary (MWTB), mean wall thickness-rosette (MWTR), mean diameter-rosette (MDR), mean wall thickness-skeleton (MWTS), and external diameter-skeleton (EDS) in preeclampsia women compared to normotensive women. There were no significant differences between preeclampsia and control group in lumen area. DiscussionWe concluded that preeclamptic chorion and chorionic villi vessels are linked with significant structural discrepancies; future studies should address morphological events that occur throughout pregnancy including associations between arterial elastic properties—mainly collagen and structural proteins in hypertensive patients. A more integrated approach involving parallel analysis of the effects of potential vasoactive factors on the morphology of foetal vessel alteration is also needed.

Progesterone prolongs time to delivery and attenuates blood pressure possibly by improving inflammation and endothelial function in response to preeclampsia

Preeclampsia (PE), new onset hypertension during pregnancy, affects 5‐7% of all pregnancies in the U.S. and is associated with reduced fetal weight, increased inflammation, vascular endothelial dysfunction (increased endothelin‐1 (ET‐1) and decreased nitric oxide (NO)) and hypertension. To date the best treatment remains early delivery of the feto‐placental unit. Activated lymphocytes during normal pregnancy (NP) express progesterone receptors, which stimulate a protein called Progesterone Induced Blocking Factor (PIBF) that is reduces during hypertensive pregnancy disorders. Therefore, this study was designed to test the hypothesis that progesterone, in the form of 17‐hydroxyprogesterone caproate (17‐OHPC), reduces inflammation, markers of endothelial dysfunction while reducing blood pressure and prolong time to delivery in PE women. In our ongoing clinical trial, PE participants received 17‐OHPC (250 mg, I.M.) with blood draws before and after injection. Placentas were collected at delivery. PIBF was 18.6 +/‐1.0 pg/mL in NT (n=4), 14.53 +/‐ 1.0 pg/mL in PE (n=10, p&lt;0.05), and 15.78 +/‐0.85 in PE+17‐OHPC (n=6). Placental CD4+ T cells were 6.5+/‐ 2.7 in PE (n=3), 4.6+/‐ 2.0 in PE +17‐OHPC (n=4). Circulating CD4+ T cells were 18.23 +/‐4.8 in PE (n=4), 14.4+/‐1.2 % gate in PE+17‐OHPC (n=5). Placental TH2 cells were 81.7+/‐10.6% gate in PE and 84.7+/‐11.0 in PE+17‐OHPC. Placental and circulating NK cells were 20.84 +/‐ 6.8 % gate, 7.2 +/‐ 2.0 in PE which reduced to 4.7+/‐1.03, 5.3 +/‐ 1.5 % gate in PE+17‐OHPC. Circulating TNF‐alpha was 32.0 +/‐ 3.4 pg/mL in PE (n=8), which decreased to 21.1+/‐5.5 in PE+17OHPC (n=4). Circulating ET‐1 was 2.53+/‐ 0.4 pg/mL in healthy normal pregnant (NP, n=5), 6.7 +/‐ 1.4 in PE (n=18, p&lt;0.05) and 4.9 +/‐ 1.3 in PE+17‐OHPC. Placenta preproendothelin ‐1 (PPET‐1) increased 1.5 fold change in PE (n=4) compared to NP, which was reduced to 0.96 in PE+17‐OHPC (n=4). Importantly, endotheling‐1 measured in HUVECS media treated with PE sera was 68 +/‐ 22 pg/mg of protein in PE which reduced to 57 +/‐19 in PE+17OHPC (n=6). Moreover, circulation nitrate‐nitrite was 50 +/‐ 9 uM in PE and significantly increased to 94 +/‐14 in PE+17‐OHPC. 17‐OHPC prolonged time of delivery beyond 72h on average and average systolic blood pressure was 151 +/‐ 5 mmHg in PE (n=18) and 137+/‐4 in PE+17‐OHPC (n=13). Our results suggest that 17‐OHPC reduced inflammation, markers of endothelial dysfunction, lowered blood pressure and prolonged time do delivery in PE women.

MATERNAL CHARACTERISTICS, FETO-MATERNAL OUTCOME AND SEASONAL VARIATION IN PRE-ECLAMPSIA WITH SEVERE FEATURES AND ECLAMPSIA

Aims&amp;objectives:- To study prevalence of pre-eclampsia, co-relation of severe pre-eclampsia and eclampsia with maternal characteristics,feto-maternal outcome,seasonal variation and sex of the fetus, if any. Materials&amp;Methoods- It was prospective observational study, carried out in obstetrics and gynecology department, MMIMSR, Mullana, Ambala, a tertiary care rural hospital in North India, from 1st June,2020 to 31st December,2020. Maternal characteristics, risk factors, sex of fetus, adverse maternal and fetal outcomes were recorded and data analyzed. Retrospective analysis of patients with severe pre-eclampsia and eclampsia, for a period of 3 years from January,2018 to December,2020 was done to see seasonal variation. Results:- A total of 1275 births were recorded from 1st June,2020 to 31st Dec,2020. 114 women were diagnosed with Hypertensive disorders of pregnancy with a prevalence of 8.94%. An increased incidence(75%) of severe pre-eclampsia/eclampsia in unbooked patients was seen. 87.5% patients were less than 30 years. 55% patients were primigravida. Severe preeclampsia-eclampsia was more in rural population(80%) with low literacy level(45%) and low socio-economic status(70%). Signicantly increased incidence(72.5%) of pre-eclampsia in women with dark complexion. 52.5% cases were seen in BMI range of 30.0-34.9. 42.5% patients presented before 34 weeks, 47.5% beyond 34 weeks and 10% within 48 hours post-partum. Singleton pregnancy was seen in 92.5% cases. Anemia was contributing factor in 42.5% and. 12.5% had APS. Caesarean rate was very high. Increased risk of severe pre-eclampsia has been observed while carrying a male fetus(67.5%). Patients with severe pre-eclampsia had increased risk of eclampsia(27.5%) and placental abruption(17.5%). FGR seen in 20%, with oligohydramnios in 15% cases. ICU admission with ventilator support needed by 10% while 5% had maternal deaths. Fetal complications, like pre-maturity seen in 50%, NICU admission required in 57.5% and intra-uterine death in 27.5%. Peak incidence recorded in summers(June-July). Conclusion-Unbooked/referred-in pregnancy, illiteracy, low socio-economic status, undiagnosed maternal risk factors, anemia pose a challenge for early diagnosis and management of severe pre-eclampsia&amp;eclampsia. Severe disease is usually early onset, more in dark complexion with male fetus in-utero with peak incidence in summer. Regular antenatal check-up with diagnosis of high-risk factors in rst trimester, to implement preventive measures should be universal guideline.