ResearchPad - preeclampsia https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Temperature and preeclampsia: Epidemiological evidence that perturbation in maternal heat homeostasis affects pregnancy outcome]]> https://www.researchpad.co/article/elastic_article_15767 This study aims to determine the association between temperature and preeclampsia and whether it is affected by seasonality and rural/urban lifestyle.MethodsThis cohort study included women who delivered at our medical center from 2004 to 2013 (31,101 women, 64,566 deliveries). Temperature values were obtained from a spatiotemporally resolved estimation model performing predictions at a 1×1km spatial resolution. In “Warm” pregnancies >50% of gestation occurred during the spring-summer period. In cold pregnancies >50% of gestation occurred during the fall and winter. Generalized estimating equation multivariable models were used to estimate the association between temperature and incidence of preeclampsia.Results1) The incidence of preeclampsia in at least one pregnancy was 7% (2173/64,566); 2) during “warm” pregnancies, an elevation of one IQR of the average temperature in the 1st or the 3rd trimesters was associated with an increased risk to develop preeclampsia [patients with Jewish ethnicity: 1st trimester: relative risk (RR) of 2.38(95%CI 1.50; 3.80), 3rd trimester 1.94(95%CI 1.34;2.81); Bedouins: 1st trimester: RR = 2.91(95%CI 1.98;4.28), 3rd trimester: RR = 2.37(95%CI 1.75;3.20)]; 3) In “cold” pregnancies, an elevation of one IQR of average temperature was associated with a lower risk to develop preeclampsia among patients with Bedouin-Arab ethnicity RR = 0.68 (95% CI 0.49–0.94) for 1st trimester and RR = 0.62 (95% CI 0.44–0.87) for 3rd trimester.Conclusions1) Elevated averaged temperature during the 1st or 3rd trimesters in “warm” pregnancies confer an increased risk for the development of preeclampsia, especially in nomadic patients; 2) Of interest, during cold pregnancies, elevated averaged temperature was associated with a lower risk to develop preeclampsia for nomadic patients. 3) These findings suggest temperature might be associated with perturbations in maternal heat homeostasis resulting in reallocation of energy resources and their availability to the fetus that may increase the risk for preeclampsia. This observation is especially relevant in the context of global warming and its effects on maternal/fetal reproductive health. ]]> <![CDATA[The role of the erythrocyte in the outcome of pregnancy with preeclampsia]]> https://www.researchpad.co/article/5c897713d5eed0c4847d23cc

The objective of this study was to analyze the relationships of osmotic and mechanical stability of erythrocytes with anthropometric, biochemical, hematologic and hemodynamic variables in pregnant women with preeclampsia (PE). The studied population consisted of 20 normotensive patients and 16 patients with PE. Patients with PE presented worse gestational outcome, greater hematologic impairment, erythrocytes osmotically more stable in vitro, but in conditions of isotonicity with the in vivo medium, in addition to hyperflow in orbital territory, when compared to normotensive patients. The correlation analysis between anthropometric, hematologic and hemodynamic variables in patients with PE indicated that erythrocytes with lower volumes and lower levels of hemoglobin favor the occurrence of a better gestational outcome, because they are more stable and because they are associated with a decrease in the hemodynamic changes present in the disease. This should mean that the tendency to microcytosis, probably due to a mechanism of compensatory mechanical selection, is a desirable characteristic in the disease.

]]>
<![CDATA[Usefulness of uterine artery Doppler velocimetry as a predictor for hypertensive disorders in pregnancy in women with prehypertension before 20 weeks gestation]]> https://www.researchpad.co/article/5c5b52d4d5eed0c4842bd0ce

Hypertensive disorders of pregnancy (HDP) is major complication of maternal-fetal outcomes in obstetric field. Although HDP is mainly defined by high blood pressure, the information about the relationship between prehypertension (preHTN, 120-139mmHg and 80-89mmHg) and HDP development is limited. The objective of this study is to determine the usefulness of preHTN before 20 weeks gestation and uterine artery (UtA) Doppler velocimetry as a predictor of HDP. A total of 2039 singleton pregnant women who had received continuous prenatal care were included in this study. The participants were classified into 2 groups based on the highest blood pressure (BP) under 20 gestational weeks as defined by the Joint National Committee 7: Normotensive (n = 1816) and preHTN pregnant women (n = 223). All preHTN pregnant women were assessed using UtA Doppler velocimetry, and the numbers of preHTN assessments were recorded. The risk of HDP was assessed in the PreHTN groups through patient history and Doppler velocimetry. Compared to normotensive patients, a total of 223 preHTN patients had a higher risk of preeclampsia (OR: 2.3; CI: 1.2–4.3), gestational hypertension (OR: 3.3; CI: 2.0–5.4) and any HDP (OR: 3.0; CI: 2.0–4.5). In the preHTN group, 134 (60.1%) patients had preHTN measured at least twice and 89 (39.9%) patients had preHTN. The results showed that two or more preHTN measurements have high sensitivity for predicting HDP (OR: 1.9; CI: 1.0–3.1; sensitivity: 83.8%; specificity: 47.2%). Additionally, the combination of abnormal UtA Doppler velocimetry results and at least two preHTN measurements showed a high accuracy in predicting HDP (OR: 2.9; CI: 1.1–4.1; sensitivity: 67.6%; specificity: 98.4%). In conclusion, close BP monitoring and recording of every preHTN event are important for pregnant women with preHTN history, and UtA Doppler examination in those women during the 2nd trimester can be a further aid in determining the risk of HDP.

]]>
<![CDATA[RNA-sequencing analysis of umbilical cord plasma microRNAs from healthy newborns]]> https://www.researchpad.co/article/5c0ed761d5eed0c484f14028

MicroRNAs are a class of small non-coding RNA that regulate gene expression at a post-transcriptional level. MicroRNAs have been identified in various body fluids under normal conditions and their stability as well as their dysregulation in disease has led to ongoing interest in their diagnostic and prognostic potential. Circulating microRNAs may be valuable predictors of early-life complications such as birth asphyxia or neonatal seizures but there are relatively few data on microRNA content in plasma from healthy babies. Here we performed small RNA-sequencing analysis of plasma processed from umbilical cord blood in a set of healthy newborns. MicroRNA levels in umbilical cord plasma of four male and four female healthy babies, from two different centres were profiled. A total of 1,004 individual microRNAs were identified, which ranged from 426 to 659 per sample, of which 269 microRNAs were common to all eight samples. Many of these microRNAs are highly expressed and consistent with previous studies using other high throughput platforms. While overall microRNA expression did not differ between male and female cord blood plasma, we did detect differentially edited microRNAs in female plasma compared to male. Of note, and consistent with other studies of this type, adenylation and uridylation were the two most prominent forms of editing. Six microRNAs, miR-128-3p, miR-29a-3p, miR-9-5p, miR-218-5p, 204-5p and miR-132-3p were consistently both uridylated and adenylated in female cord blood plasma. These results provide a benchmark for microRNA profiling and biomarker discovery using umbilical cord plasma and can be used as comparative data for future biomarker profiles from complicated births or those with early-life developmental disorders.

]]>
<![CDATA[Association of pre-eclampsia risk with maternal levels of folate, homocysteine and vitamin B12 in Colombia: A case-control study]]> https://www.researchpad.co/article/5c12cf01d5eed0c484913cf4

Background

Maternal serum concentrations of folate, homocysteine, and vitamin B12 have been associated with pre-eclampsia. Nevertheless, reported studies involve limited number of cases to reliably assess the nature of these associations. Our aim was to examine the relation of these three biomarkers with pre-eclampsia risk in a large Colombian population.

Materials and methods

Design: A case-control study.

Setting: Cases of pre-eclampsia and healthy pregnant controls were recruited at the time of delivery from eight different Colombian cities between 2000 and 2012.

Population or Sample: 2978 cases and 4096 controls were studied. Maternal serum concentrations of folate, homocysteine, and vitamin B12 were determined in 1148 (43.6%) cases and 1300 (31.7%) controls. Also, self-reported folic acid supplementation was recorded for 2563 (84%) cases and 3155 (84%) controls.

Analysis: Adjusted odds ratios (OR) for pre-eclampsia were estimated for one standard deviation (1SD) increase in log-transformed biomarkers. Furthermore, we conducted analyses to compare women that reported taking folic acid supplementation for different periods during pregnancy.

Main Outcomes Measures: Odds ratio for pre-eclampsia.

Results

After adjusting for potential confounders in logistic regression models, the OR for pre-eclampsia was 0.80 (95% CI: 0.72, 0.90) for 1SD increase in log-folate, 1.16 (95%CI: 1.05, 1.27) for 1SD increase in log-homocysteine, and 1.10 (95%CI: 0.99, 1.22) for 1SD increase in log-vitamin B12. No interactions among the biomarkers were identified. Women who self-reported consumption of folic acid (1 mg/day) throughout their pregnancy had an adjusted OR for pre-eclampsia of 0.86 (95%CI: 0.67, 1.09) compared to women that reported no consumption of folic acid at any point during pregnancy.

Conclusions

Maternal serum concentrations of folate were associated as a protective factor for pre-eclampsia while concentrations of homocysteine were associated as a risk factor. No association between maternal vitamin B12 concentrations and preeclampsia was found.

]]>
<![CDATA[Long-Term Outcomes of Systemic Lupus Erythematous Patients after Pregnancy: A Nationwide Population-Based Cohort Study]]> https://www.researchpad.co/article/5989da44ab0ee8fa60b8b247

Background

Data on long-term maternal outcomes in patients with systemic lupus erythematosus (SLE) are lacking. The study aimed to explore the relationships among SLE, pregnancy, outcomes of end-stage renal disease (ESRD), and overall mortality.

Methods

We established a retrospective cohort study consisting of four cohorts: pregnant (case cohort) and nonpregnant SLE patients, as well as pregnant and nonpregnant non-SLE patients. One case cohort and three comparison cohorts were matched by age at first pregnancy and index date of pregnancy by using the Taiwan National Health Insurance Research Dataset. All study subjects were selected based on the index date to the occurrence of ESRD or overall death. Cox proportional hazard regression models and Kaplan–Meier curves were used in the analysis.

Results

SLE pregnant patients exhibited significantly increased risk of ESRD after adjusting for other important confounders, including immunosuppressant and parity (HR = 3.19, 95% CI: 1.35–7.52 for pregnant non-SLE; and HR = 2.77, 95% CI: 1.24–6.15 for nonpregnant non-SLE patients). No significant differences in ESRD incidence were observed in pregnant and nonpregnant SLE patients. Pregnant SLE patients exhibited better clinical condition at the baseline and a significantly lower risk of overall mortality than nonpregnant SLE patients.

Conclusions

Our data support current recommendations for SLE patients to avoid pregnancy until disease activity is quiescent. Multicenter recruitment and clinical information can be used to further examine the association of SLE and ESRD (or mortality) after pregnancy.

]]>
<![CDATA[The Pre-Eclampsia Ontology: A Disease Ontology Representing the Domain Knowledge Specific to Pre-Eclampsia]]> https://www.researchpad.co/article/5989da54ab0ee8fa60b8e924

Pre-eclampsia (PE) is a clinical syndrome characterized by new-onset hypertension and proteinuria at ≥20 weeks of gestation, and is a leading cause of maternal and perinatal morbidity and mortality. Previous studies have gathered abundant data about PE such as risk factors and pathological findings. However, most of these data are not semantically structured. Clinical data on PE patients are often generated with semantic heterogeneity such as using disparate terminology to describe the same phenomena. In clinical studies, interoperability of heterogenic clinical data is required in various situations. In such a situation, it is necessary to develop an interoperable and standardized semantic framework to research the pathology of PE more comprehensively and to achieve interoperability of heterogenic clinical data of PE patients. In this study, we developed an ontology representing clinical features, treatments, genetic factors, environmental factors, and other aspects of the current knowledge in the domain of PE. We call this pre-eclampsia ontology “PEO”. To achieve interoperability with other ontologies, the core structure of PEO was compliant with the hierarchy of the Basic Formal Ontology (BFO). The PEO incorporates a wide range of key concepts and terms of PE from clinical and biomedical research in structuring the knowledge base that is specific to PE; therefore, PEO is expected to enhance PE-specific information retrieval and knowledge discovery in both clinical and biomedical research fields.

]]>
<![CDATA[Preeclampsia: A risk factor for gestational diabetes mellitus in subsequent pregnancy]]> https://www.researchpad.co/article/5989db5cab0ee8fa60bdff70

Preeclampsia and gestational diabetes (GDM) have several mechanisms in common. The aim of this study was to determine whether women with preeclampsia have an increased risk of GDM in a subsequent pregnancy. Study data were collected from the Korea National Health Insurance Claims Database of the Health Insurance Review and Assessment Service for 2007–2012. Patients who had their first delivery in 2007 and a subsequent delivery between 2008 and 2012 in Korea were enrolled. A model of multivariate logistic regression analysis was performed with GDM as the final outcome to evaluate the risk of GDM in the second pregnancy. Among the 252,276 women who had their first delivery in 2007, 150,794 women had their second delivery between 2008 and 2012. On the multivariate regression analysis, women with preeclampsia alone in the first pregnancy had an increased risk of GDM in the second pregnancy when compared with women who had neither of these conditions in their first pregnancy (OR 1.2, 95% CI, 1.1–1.3). Women with GDM alone in the first pregnancy were at an increased risk for GDM in the second pregnancy (OR 3.3, 95% CI 3.1–3.4). The co-presence of preeclampsia and GDM in the first pregnancy further increased the risk of GDM in the second pregnancy (OR 5.9, 95% CI, 4.0–8.6). Our study showed that a history of preeclampsia may serve as an additional risk factor for GDM in a subsequent pregnancy.

]]>
<![CDATA[Plasma cross-gestational sphingolipidomic analyses reveal potential first trimester biomarkers of preeclampsia]]> https://www.researchpad.co/article/5989db52ab0ee8fa60bdc502

Introduction

Preeclampsia (PE) is a gestational disorder, manifested in the second half of pregnancy by maternal hypertension, proteinuria and generalized edema. PE is a major cause of maternal and fetal morbidity and mortality, accounting for nearly 40% of all premature births worldwide. Bioactive sphingolipids are emerging as key molecules involved in etiopathogenesis of PE, characterized by maternal angiogenic imbalance and symptoms of metabolic syndrome. The aim of this study was to compare the cross-gestational profile of circulating bioactive sphingolipids in maternal plasma from preeclamptic (PE) versus normotensive control (CTL) subjects with the goal of identifying sphingolipids as candidate first trimester biomarkers of PE for early prediction of the disease.

Methods

A prospective cohort of patients was sampled at the first, second and third trimester of pregnancy for each patient (11–14, 22–24, and 32–36 weeks´ gestation). A retrospective stratified study design was used to quantify different classes of sphingolipids in maternal plasma. We used a reverse-phase high-performance liquid chromatography-tandem mass spectrometry (HPLC-ESI-MS/MS) approach for determining different sphingolipid molecular species (sphingosine-1-phosphate (S1P), dihydro-sphingosine-1-phosphate (DH-S1P), sphingomyelins (SM) and ceramides (Cer)) in cross-gestational samples of human plasma from PE (n = 7, 21 plasma samples across pregnancy) and CTL (n = 7, 21 plasma samples across pregnancy) patients.

Results

Plasma levels of angiogenic S1P did not change significantly in control and in preeclamptic patients´ group across gestation. DH-S1P was significantly decreased in second trimester plasma of PE patients in comparison to their first trimester, which could contribute to reduced endothelial barrier observed in PE. The major ceramide species (Cer 16:0 and Cer 24:0) tended to be up-regulated in plasma of control and PE subjects across gestation. The levels of a less abundant plasma ceramide species (Cer 14:0) were significantly lower in first trimester plasma of PE patients when compared with their gestational-matched control samples (p = 0.009). Major plasma sphingomyelin species (SM 16:0, SM 18:1 and SM 24:0) tended to be higher in control pregnancies across gestation. However, in PE patients, SM 16:0, SM 18:0 and SM 18:1 showed significant up-regulation across gestation, pointing to atherogenic properties of the sphingomyelins and particularly the potential contribution of SM 18:0 to the disease development. In addition, two major sphingomyelins, SM 16:0 and SM 18:0, were significantly lower in first trimester plasma of PE patients versus first trimester samples of respective controls (p = 0.007 and p = 0.002, respectively).

Conclusions

Cross-gestational analysis of maternal plasma of preeclamptic and normotensive women identifies differences in the biochemical profile of major sphingolipids (DH-S1P, sphingomyelins and ceramides) between these two groups. In addition, first trimester maternal plasma sphingolipids (Cer 14:0, SM 16:0 and SM 18:0) may serve in the future as early biomarkers of PE occurrence and development.

]]>
<![CDATA[Genome-Wide Identification of Epigenetic Hotspots Potentially Related to Cardiovascular Risk in Adult Women after a Complicated Pregnancy]]> https://www.researchpad.co/article/5989d9e2ab0ee8fa60b6a02f

Background

The physiological demands of pregnancy on the maternal cardiovascular system can catapult women into a metabolic syndrome that predisposes to atherosclerosis in later life. We sought to identify the nature of the epigenomic changes associated with the increased cardiovascular disease (CVD) risk in adult women following pre-eclampsia.

Findings

We assessed the genome wide epigenetic profile by methyl-C sequencing of monozygotic parous twin sister pairs discordant for a severe variant of pre-eclampsia. In the adult twin sisters at risk for CVD as a consequence of a complicated pregnancy, a set of 12 differentially methylated regions with at least 50% difference in methylation percentage and the same directional change was found to be shared between the affected twin sisters and significantly different compared to their unaffected monozygous sisters.

Conclusion

The current epigenetic marker set will permit targeted analysis of differentially methylated regions potentially related to CVD risk in large cohorts of adult women following complicated pregnancies.

]]>
<![CDATA[Longitudinal changes of ocular blood flow using laser speckle flowgraphy during normal pregnancy]]> https://www.researchpad.co/article/5989db50ab0ee8fa60bdbd21

Purpose

Innovative laser speckle flowgraphy (LSFG) enables noninvasive evaluation of retinal microcirculation and the usefulness has been reported in the field of ophthalmology. LSFG has allowed us to measure the real time changes of retinal blood flow without pupillary dilatations and contrast media. Herein, we investigated the change of retinal blood flow in normal pregnant women during gestation using LSFG.

Methods

A prospective cohort study was conducted in 53 pregnant women who visited our institution between January, 2013 and July, 2014. Finally, a total of 41 participants without any obstetric complications were available for evaluation. Retinal blood flow was measured with LSFG in a total of 4 times during pregnancy (T1. 11–13 weeks, T2. 19–21 weeks, T3. 28–30 weeks, T4. 34–36 weeks) and mean blur rate (MBR), blowout score (BOS), flow acceleration index (FAI), and resistive index (RI) are analyzed from these measurements. Relations between LSFG parameters and mean arterial blood pressure (MAP) are determined throughout pregnancy.

Results

MBR showed no significant changes throughout pregnancy. BOS showed a tendency to increase in the 3rd trimester. FAI values showed a slight increase from the 1st to 2nd trimester while a significant decrease was noted in the 3rd trimester. RI exhibited no changes between the 1st and 2nd trimesters, values decreased significantly after the 3rd trimester. MAP was positively correlated with BOS, and negatively correlated with FAI and RI.

Conclusion

The present study clearly demonstrated that profiles of LSFG parameters demonstrated a decrease of resistance in retinal blood vessels. These changes in indices provide a highly sensitive reflection of physiological changes in vascular resistance due to pregnancy. Thus, LSFG may be useful, as a non-invasive, diagnostic tool to detect pregnancy related disorders such as preeclampsia.

]]>
<![CDATA[Plasma Level of Placenta-Derived Macrophage-Stimulating Protein -Chain in Preeclampsia before 20 Weeks of Pregnancy]]> https://www.researchpad.co/article/5989db13ab0ee8fa60bccb03

Object

This study aimed to investigate the diagnostic value of placenta-derived macrophage-stimulating protein α-chain (MSP-α) before the 20th week of gestation for the early diagnosis of preeclampsia (PE).

Methods and Materials

Two parts of this nested case-control study were simultaneously executed, and 1500 pregnant women were recruited. A total of 124 pregnant women were included in the plasma analysis part of this study. The MSP-α plasma level was measured before the 20th week of gestation, and the participants were followed until delivery. A case group of 62 women with PE and a control group of 62 women matched by gestational age, maternal age, and pre-pregnancy BMI (with normotensive pregnancies) were evaluated. In the placenta analysis part of this nested case-control study, the placentas of 34 pregnant women were randomly obtained. The placental levels of MSP were measured in 17 individuals with PE (case group) and in 17 women with a normotensive pregnancy matched by gestational age and maternal age (control group).

Results

The plasma level of MSP-α was higher in the PE group than in the control group before the 20th week of gestation (p < 0.001). In addition, compared to the women with severe features in the PE group, those without severe features had a significantly higher plasma MSP-α level before the 20th week of gestation (p < 0.001). The area under the receiver operating characteristic curve (AUC) of MSP-α before the 20th week of gestation was 0.905 (95% CI, 0.811–0.962) for the women with early-onset PE without severe features. With regard to the placenta, the PE group (accumulated optical density, IOD [SUM] = 8862.37 ± 2064.42) exhibited increased MSP staining (more intense MSP staining or more extensive staining) compared with the control group (normal pregnancies (IOD [SUM] = 447.92 ± 114.72, P < 0.001). Furthermore, increased MSP staining was detected among the women without severe features compared with those with severe features in the PE group (IOD [SUM]: 12192.65 ± 5325.56 vs. 4104.83 ± 2383.06, P = 0.021).

Conclusion

According to the findings of this study, the plasma level of MSP-α may be associated with PE, and MSP-α may be considered a candidate protein for further analysis in studies of PE. Multicenter studies with larger sample sizes must be performed in the future to obtain accurate results regarding the predictive value of MSP-α in combination with other protein factors for the early diagnosis of PE.

]]>
<![CDATA[The Role of the Carbohydrate Recognition Domain of Placental Protein 13 (PP13) in Pregnancy Evaluated with Recombinant PP13 and the DelT221 PP13 Variant]]> https://www.researchpad.co/article/5989daacab0ee8fa60ba9a5b

Introduction

Placental protein 13 (PP13), a placenta specific protein, is reduced in the first trimester of pregnancy in women who subsequently develop preeclampsia. A naturally occurring PP13 deletion of thymidine at position 221 (DelT221 or truncated variant) is associated with increased frequency of severe preeclampsia. In this study we compared the full length (wildtype) PP13 and the truncated variant.

Methods

Full length PP13 or its DelT221 variant were cloned, expressed and purified from E-Coli. Both variants were administrated into pregnant rats at day 8 of pregnancy for slow release (>5 days) through osmotic pumps and rat blood pressure was measured. Animals were sacrificed at day 15 or day 21 and their utero-placental vasculature was examined.

Results

The DelT221 variant (11 kDA) lacked exon 4 and a part of exon 3, and is short of 2 amino acids involved in the carbohydrate (CRD) binding of the wildtype (18 kDA). Unlike the wildtype PP13, purification of DelT221 variant required special refolding. PP13 specific poly- clonal antibodies recognized both PP13 and DelT221 but PP13 specific monoclonal antibodies recognized only the wildtype, indicating the loss of major epitopes. Wildtype PP13 mRNA and its respective proteins were both lower in PE patients compared to normal pregnancies. The DelT221 mutant was not found in a large Caucasian cohort. Pregnant rats exposed to wildtype or DelT221 PP13 variants had significantly lower blood pressure compared to control. The wildtype but not the DelT221 mutant caused extensive vein expansion.

Conclusion

This study revealed the importance of PP13 in regulating blood pressure and expanding the utero-placental vasculature in pregnant rats. PP13 mutant lacking amino acids of the PP13 CRD domain fails to cause vein expansion but did reduce blood pressure. The study provides a basis for replenishing patients at risk for preeclampsia by the full length but not the truncated PP13.

]]>
<![CDATA[Lipidomic Assessment of Plasma and Placenta of Women with Early-Onset Preeclampsia]]> https://www.researchpad.co/article/5989da59ab0ee8fa60b8f89b

Introduction

Adipose tissue is responsible for triggering chronic systemic inflammatory response and these changes may be involved in the pathophysiology of preeclampsia.

Objective

To characterize the lipid profile in the placenta and plasma of patients with preeclampsia.

Methodology

Samples were collected from placenta and plasma of 10 pregnant women with preeclampsia and 10 controls. Lipids were extracted using the Bligh–Dyer protocol and were analysed by MALDI TOF-TOF mass spectrometry.

Results

Approximately 200 lipid signals were quantified. The most prevalent lipid present in plasma of patients with preeclampsia was the main class Glycerophosphoserines-GP03 (PS) representing 52.30% of the total lipid composition, followed by the main classes Glycerophosphoethanolamines-GP02 (PEt), Glycerophosphocholines-GP01 (PC) and Flavanoids-PK12 (FLV), with 24.03%, 9.47% and 8.39% respectively. When compared to the control group, plasma samples of patients with preeclampsia showed an increase of PS (p<0.0001), PC (p<0.0001) and FLV (p<0.0001). Placental analysis of patients with preeclampsia, revealed the PS as the most prevalent lipid representing 56.28%, followed by the main class Macrolides/polyketides-PK04 with 32.77%, both with increased levels when compared with patients control group, PS (p<0.0001) and PK04 (p<0.0001).

Conclusion

Lipids found in placenta and plasma from patients with preeclampsia differ from those of pregnant women in the control group. Further studies are needed to clarify if these changes are specific and a cause or consequence of preeclampsia.

]]>
<![CDATA[Semaphorin 3F expression is reduced in pregnancy complicated by preeclampsia. An observational clinical study]]> https://www.researchpad.co/article/5989db50ab0ee8fa60bdc177

Background and objective

Preeclampsia is a systemic disorder, affecting 2–10% of pregnancies, characterized by a deregulated pro- and anti-angiogenic balance. Semaphorin 3F is an angiogenesis inhibitor. We aimed to investigate whether semaphorin 3F expression is modulated in preeclampsia.

Design, setting, participants, and measurements

We performed two observational single center cohort studies between March 2013 and August 2014. In the first we enrolled 110 consecutive women, undergoing an elective cesarean section; in the second we included 150 consecutive women undergoing amniocentesis for routine clinical indications at 16–18 week of gestation. Semaphorin 3F concentration was evaluated in maternal peripheral blood, venous umbilical blood and amniotic fluid, along with its placenta protein expression at the time of delivery in the first study group and in the amniotic fluid at 16–18 weeks of gestation in the second study group.

Results

In the first study 19 patients presented at delivery with preeclampsia. Semaphorin 3F placenta tissue expression was significantly reduced in preeclampsia. In addition, semaphorin 3F level at delivery was significantly lower in serum, amniotic fluid and venous umbilical blood of preeclamptic patients compared with normal pregnant women. In the prospective cohort study 14 women developed preeclampsia. In this setting, semaphorin 3F amniotic level at 16–18 weeks of gestation was reduced in women who subsequently developed preeclampsia compared to women with a normal pregnancy. ROC curve analysis showed that semaphorin 3F amniotic levels could identify women at higher risk of preeclampsia.

Conclusions

Semaphorin 3F might represent a predictive biomarker of preeclampsia.

]]>
<![CDATA[Interdependence of JAK-STAT and MAPK signaling pathways during EGF-mediated HTR-8/SVneo cell invasion]]> https://www.researchpad.co/article/5989db5cab0ee8fa60be002c

Invasion of trophoblast cells is spatio-temporally regulated by various cytokines and growth factors. In pregnancy, complications like preeclampsia, shallow invasion of trophoblast cells and low amounts of epidermal growth factor (EGF) have been reported. In the present study, regulatory mechanisms associated with EGF-mediated invasion in HTR-8/SVneo trophoblastic cells have been delineated. Treatment of HTR-8/SVneo cells with EGF (10 ng/ml) led to eight fold increase (p < 0.05) in invasion. Increased invasion of HTR-8/SVneo cells by EGF was associated with an increase in phosphorylation of ERK½. In addition, significant phosphorylation of STAT1 (ser 727) and STAT3 (both tyr 705 and ser 727 residues) was also observed, accompanied by a decrease in total STAT1. Inhibition of ERK½ phosphorylation by U0126 (10 μM) led to a significant decrease in EGF-mediated invasion with simultaneous decrease in the phosphorylated forms of STAT3 and STAT1. Decrease in total STAT1 was also reversed on inhibition of ERK½. Interestingly, inhibition of STAT3 by siRNA led to a significant decrease in EGF-mediated invasion of HTR-8/SVneo cells and phosphorylation of STAT1, but it did not have any effect on the activation of ERK½. On the other hand, inhibition of STAT1 by siRNA, also led to a significant decrease in the EGF-mediated invasion of HTR-8/SVneo cells, showed concomitant decrease in ERK½ phosphorylation and STAT3 phosphorylation at ser 727 residue. These results suggest cross-communication between ERK½ and JAK-STAT pathways during EGF-mediated increase in invasion of trophoblast cells; phosphorylation at ser 727 residue of both STAT3 and STAT1 appears to be critical.

]]>
<![CDATA[Comparison of risk factors and outcomes of gestational hypertension and pre-eclampsia]]> https://www.researchpad.co/article/5989db54ab0ee8fa60bdd155

Background

It remains an enigma whether gestational hypertension (GH) and pre-eclampsia (PE) are distinct entities or different spectrum of the same disease. We aimed to compare the risk factors and outcomes between GH and PE.

Method

A total of 7,633 pregnant women recruited between 12 and 20 weeks of gestation in the Ottawa and Kingston Birth Cohort from 2002 to 2009 were included in the analysis. Cox proportional hazards model was used to identify and compare the risk factors for GH and PE by treating gestational age at delivery as the survival time. Logistic regression model was used to compare outcome. Subgroup analysis was performed for early- and late-onset PE.

Results

GH and PE shared most risk factors including overweight and obesity, nulliparity, PE history, type 1 and 2 diabetes, and twin birth. Effect size of PE history (RR = 14.1 for GH vs. RR = 6.4 for PE) and twin birth (RR = 4.8 for GH vs. RR = 10.3 for PE) showed substantial difference. Risk factors modified gestational age at delivery in patients with GH and PE in similar pattern. Subgroup analysis showed that early- and late-onset PE shared some risk factors with different effect sizes, whereas folic acid supplementation showed protective effect for early-onset PE only. PE was strongly associated with several adverse outcomes including cesarean section, placental abruption, small for gestational age, preterm birth, and 5 min Apgar score < 7, whereas GH was associated with increased risk of preterm birth only.

Conclusions

GH and PE shared common risk factors. Differences in effect sizes of risk factors and outcomes indicate that the conditions may have different pathophysiology and mechanism.

]]>
<![CDATA[miR-125b Enhances IL-8 Production in Early-Onset Severe Preeclampsia by Targeting Sphingosine-1-Phosphate Lyase 1]]> https://www.researchpad.co/article/5989dad5ab0ee8fa60bb7abf

Preeclampsia (PE) is one of the leading causes of maternal and perinatal mortality and morbidity. One of the main hallmarks observed in PE is impaired inflammation state. In the current study, we found that miR-125b was deregulated in placental tissues and plasma derived from PE patients, which suggest a potential association between this miRNA and the pathogenesis of PE. Overexpression of miR-125b significantly reduced SGPL1 expression, and luciferase assays confirmed that SGPL1 is a direct target of miR-125b. We also found that miR-125b enhanced IL-8 production by directly targeting sphingosine-1-phosphate lyase 1 (SGPL1), and this effect could be reversed by SGPL1 overexpression. In placentas derived from PE patients, a negative correlation of miR-125b and SGPL1 was observed, and IL-8 was validated to be increased in the circulation of PE patients. Our data demonstrated a critical role of miR-125b in IL-8 production and the development of PE.

]]>
<![CDATA[Fatty Acid Oxidation Changes and the Correlation with Oxidative Stress in Different Preeclampsia-Like Mouse Models]]> https://www.researchpad.co/article/5989da8eab0ee8fa60b9ef12

Background

Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) expression is decreased in placenta of some cases of preeclampsia (PE) which may result in free fatty acid (FFA) increased. High FFA level will induce oxidative stress, so abnormal long-chain fatty acid-oxidation may participate in the pathogenesis of PE through oxidative stress pathway.

Methods

PE-like groups were ApoC3 transgenic mice with abnormal fatty acid metabolism, classical PE-like models with injection of Nw-nitro-L-arginine-methyl ester (L-NA) or lipopolysaccharide (LPS) and the antiphospholipid syndrome (APS) mouse model with β2GPI injection (ApoC3+NS, ApoC3+L-NA, L-NA, LPS and β2GPI groups). The control group was wild-type mice with normal saline injection. Except for β2GPI mice, the other mice were subdivided into pre-implantation (Pre) and mid-pregnancy (Mid) subgroups by injection time.

Results

All PE-like groups showed hypertension and proteinuria except ApoC3+NS mice only showed hypertension. Serum FFA levels increased significantly except in LPS group compared to controls (P<0.05). LCHAD mRNA and protein expression in the liver and placenta was significantly higher for ApoC3+NS, ApoC3+L-NA and β2GPI mice and lower for L-NA mice than controls (P<0.05) but did not differ between LPS mice and controls. P47phox mRNA and protein expression in the liver significantly increased in all PE-like groups except LPS group, while P47phox expression in the placenta only significantly increased in L-NA and β2GPI groups.

Conclusions

Abnormal long-chain fatty acid-oxidation may play a different role in different PE-like models and in some cases participate in the pathogenesis of PE through oxidative stress pathway.

]]>
<![CDATA[Serum Calcium, Magnesium, Zinc and Copper Levels in Sudanese Women with Preeclampsia]]> https://www.researchpad.co/article/5989d9feab0ee8fa60b7314e

Background

Although the exact pathophysiology of preeclampsia is not fully understood, several elemental micronutrient abnormalities have been suggested to play a contributory role in preeclampsia.

Aims

To investigate the levels of calcium, magnesium, zinc and copper in women with preeclampsia.

Subjects and Methods

A case—control study was conducted in Omdurman Maternity Hospital, Sudan, during the period of September through December 2014. The cases were women with preeclampsia while healthy pregnant women were the controls. The medical and obstetrics history was gathered using questionnaires. The serum levels of calcium, magnesium, zinc and copper were measured using atomic absorption spectrophotometer.

Results

There was no significant difference between the two groups in their age, gestational age, parity and body mass index. Zinc and copper levels were not significantly different between the two groups. In comparison with the controls, women with preeclampsia had a significantly lower median (inter-quartile) serum calcium [7.6 (4.0─9.6) vs. 8.1 (10.6─14.2), mg/dl, P = 0.032] and higher levels of magnesium [1.9 (1.4─2.5) vs. 1.4 (1.0─1.9) mg/dl; P = 0.003]. In binary logistic regression, lower calcium (OR = 0.73, 95% CI = 0.56 ─ 0.95, P = 0.021) and higher magnesium (OR = 5.724, 95% CI = 1.23 ─ 26.50, P = 0.026) levels were associated with preeclampsia. There were no significant correlations between levels of hemoglobin and these trace elements.

Conclusion

The current study showed significant associations between preeclampsia and serum levels of calcium and magnesium.

]]>