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1.
OBJECTIVE: To estimate whether alterations in plasma levels of the proangiogenic proteins placental growth factor (PlGF) and vascular endothelial growth factor-A (VEGF-A), and the antiangiogenic protein soluble fms-like tyrosine kinase-1 (sFlt1) were more pronounced in early-onset than in late-onset preeclampsia. METHODS: A cross-sectional study was conducted to estimate the levels of sFlt1, PlGF, and VEGF-A in plasma in a control group of nonpregnant women, in an early control group of women at 24-32 weeks of gestation, in a late control group of women at 36-42 weeks of gestation, and in cases of women with early-onset (before 32 weeks of gestation) and late-onset (after 35 weeks of gestation) preeclampsia. RESULTS: Women with early-onset preeclampsia had a 43 times higher median plasma sFlt1 level than early controls (P<.001). Women with late-onset preeclampsia had a three times higher median plasma sFlt1 level than late controls (P<.001). Women with early-onset preeclampsia had a 21 times lower median plasma PlGF level than early controls (P<.001). Women with late-onset preeclampsia had a five times lower median plasma PlGF level than late controls (P=.01). The median level of VEGF-A in plasma was less than 15 pg/mL in all groups of pregnant women. CONCLUSION: Both early- and late-onset preeclampsia are associated with altered plasma levels of sFlt1 and PlGF. The alterations are more pronounced in early-onset rather than in late-onset disease.  相似文献   

2.
Preeclampsia (PE), a specific syndrome of pregnancy, can be classified into early and late onset, depending on whether clinical manifestations occur before or after 34 weeks’ gestation. We determined whether plasma concentrations of Hsp60 and Hsp70 were related to circulating cytokine levels, as well as kidney and liver functions, in early- and late-onset PE. Two hundred and thirty-seven preeclamptic women (95 with early- and 142 with late-onset PE) were evaluated. Plasma levels of Hsp60, Hsp70, and their specific antibodies, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1, IL-10, IL-12, and soluble TNF-α-receptor I (sTNFRI) concentrations, were determined by enzyme-linked immunosorbent assay (ELISA). Concentrations of Hsp70, TNF-α, IL-1β, IL-12, and sTNFRI were significantly elevated in patients with early-onset PE compared with women with late-onset PE; IL-10 levels were significantly lower in the early-onset PE group. Concentrations of urea, uric acid, proteinuria, glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), and lactate dehydrogenase (LDH) were also significantly higher in early-onset PE. The percentage of infants with intrauterine growth restriction was also significantly higher in women with early-onset PE. There were positive correlations between Hsp70 levels and TNF-α, TNFRI, IL-1β, IL-12, GOT, GPT, LDH, and uric acid concentrations in early-onset PE group. Thus, early-onset PE was associated with greater maternal and fetal impairment. There are differences in pathophysiology between early- and late-onset PE, highlighting by the difference in Hsp70 levels.  相似文献   

3.
OBJECTIVE: To determine whether alterations in second-trimester maternal serum cytokine concentrations can identify women at risk for developing severe, early-onset preeclampsia. METHODS: Patients with severe preeclampsia requiring delivery prior to 34 weeks (n = 20) were each matched by gestational age, gravidity, parity, and sample freezing time with three healthy controls who delivered at term (n = 60). By using second-trimester maternal sera originally collected for fetal aneuploidy screening, the concentrations of placental growth factor, vascular endothelial growth factor, granulocyte colony-stimulating factor, endothelin-1, and human chorionic gonadotropin were compared between patients and controls. Logistic regression analysis was used to estimate odds ratios for high versus low (median split) cytokine concentrations with respect to the development of severe, early-onset preeclampsia. Receiver operating characteristic (ROC) curves based on a second logistic regression, using actual cytokine values, were plotted to illustrate reciprocal impact on sensitivity and specificity. RESULTS: Placental growth factor and vascular endothelial growth factor levels were significantly lower in patients than in controls. No significant differences were observed for the other cytokines. The odds ratios (with 95% confidence intervals) were 15.54 (3.29, 73.40) for vascular endothelial growth factor and 4.20 (1.35, 13.06) for placental growth factor. Receiver operating characteristic analysis of placental growth factor and vascular endothelial growth factor confirmed that both were useful in discriminating between patients and controls. Models combining both vascular endothelial growth factor and placental growth factor provided the best performance for identifying patients at risk for developing severe, early-onset preeclampsia, according to both odds ratios and ROC analyses. CONCLUSION: Combined analysis of placental growth factor and vascular endothelial growth factor is potentially useful as a tool for early identification of patients at risk for developing severe, early-onset preeclampsia.  相似文献   

4.
Purpose: Increased inflammatory response and cytokines are claimed to play a significant role in the etiology of preeclampsia. Interleukin-6 (IL-6) is a proinflammatory cytokine. Limited number of studies evaluating IL-6 levels in preeclamptic patients have produced conflicting results. Therefore, the present study sought to compare maternal and umbilical cord serum levels of IL-6 in early- and late-onset preeclamptic pregnancies as well as in normal pregnancies. Materials and methods: A total of 69 participants were enrolled in the study. The control group consisted of 24 participants with normal pregnancies. Preeclampsia group consisted of 45 participants. The preeclampsia group was further classified into the subgroups of early- and late-onset preeclampsia. Late-onset preeclampsia group consisted of 24 women whereas early-onset preeclampsia group consisted of 21 women. Serum and umbilical cord samples of IL-6 were compared. Results: There was no significant difference between maternal and umbilical cord serum IL-6 concentrations between the preeclampsia and control group. No significant difference was observed in maternal and umbilical cord serum IL-6 levels between early- and late-onset preeclampsia groups. Conclusion: Our results do not support an increase in IL-6 levels in patients with early- and late-onset preeclampsia. The clinical relevance of our findings needs to be further investigated.  相似文献   

5.
OBJECTIVE: Soluble vascular endothelial growth factor receptor 1 (sVEGFR-1), which antagonizes VEGF functions, has been implicated in the pathophysiology of preeclampsia. The purpose of this study was to determine whether preeclampsia is associated with a change in the plasma concentration of sVEGFR-1, and, if so, whether such a change is correlated with the severity of the disease. METHODS: A cross-sectional study was conducted to determine the concentrations of sVEGFR-1 in plasma obtained from normal pregnant women (n=61) and patients with preeclampsia (n=61). Plasma concentrations of sVEGFR-1 were determined by enzyme-linked immunoassay. RESULTS: Preeclampsia had a higher median plasma concentration of sVEGFR-1 than normal pregnancy (P <.001). The median plasma concentration of sVEGFR-1 was higher in early-onset (< or =34 weeks) than late-onset (>34 weeks) preeclampsia (P=.005), and higher in severe than in mild preeclampsia (P=.002). In normal pregnancy, there was a correlation between plasma concentration of sVEGFR-1 and gestational age (r=0.5; P <.001). In contrast, there was a negative correlation between plasma concentration of sVEGFR-1 and gestational age at the onset of preeclampsia (r=-0.5; P <.001). CONCLUSION: Preeclampsia is associated with an increased plasma sVEGFR-1 concentration. The elevation of sVEGFR-1 concentration is correlated with the severity of the disease. These observations suggest the participation of VEGF and its soluble receptor in the pathophysiology of preeclampsia.  相似文献   

6.
ObjectivePreeclampsia is associated with a higher maternal blood levels of soluble fms-like tyrosine kinase-1 (sFlt-1) and lower levels of placental growth factor (PlGF) that appear before clinical onset. We aimed to estimate the normal progression of these biomarkers in normal pregnancies and in those affected by preeclampsia.MethodsWe conducted a case-cohort study including low-risk nulliparous women recruited at 11–13 weeks gestation (cohort) and women with preeclampsia (cases). Maternal blood was collected at different points during pregnancy including at the time of diagnosis of preeclampsia for cases. Maternal serum PlGF and sFlt-1 concentrations and the sFlt-1/PlGF ratio were measured using B•R•A•H•M•S plus KRYPTOR automated assays and were compared between patients in both groups matched for gestational age. Cases were stratified as early- (≤34 weeks), intermediate- (35–37 weeks) and late-onset (>37 weeks) preeclampsia.ResultsThe cohort consisted of 45 women whose results were compared with those of 31 women who developed preeclampsia, diagnosed at a median gestational age of 32 weeks (range 25–38 weeks). We observed that sFlt-1, PlGF and their ratio fluctuated during pregnancy in both groups, with a significant correlation with gestational age after 28 weeks (P < 0.05). We observed a significant difference between cases and controls, with a median ratio 100 times higher in early preeclampsia (P < 0.001), 13 times higher in intermediate preeclampsia (P < 0.001), but no significant difference between groups in late-onset preeclampsia with matched controls.ConclusionPlGF, sFlt-1, and their ratio may be useful in the prediction and diagnosis of early- and intermediate-onset preeclampsia but are not useful for late-onset preeclampsia.  相似文献   

7.
目的:研究重度子痫前期(PE)患者血清髓过氧化物酶(MPO)及超敏C反应蛋白(hs-CRP)水平与新生儿出生体重的关系。方法:选择2012年1~10月于我院产科住院分娩的60例重度PE孕妇,按发病时孕周不同分为早发型PE组(发病时孕周34周)和晚发型PE组(发病时孕周≥34周)各30例;另选同期正常晚期妊娠孕妇60例,根据孕周不同分为早发型(对照1组)和晚发型(对照2组)各30例。采用酶联免疫吸附(ELISA)法检测血清MPO水平,采用散射比浊法测定hs-CRP。结果:(1)早发型及晚发型PE组孕妇的血清MPO水平高于对照1组及对照2组,4组比较差异有统计学意义(P0.05);且早发型高于晚发型PE组,差异有统计学意义(P0.05);但对照1组与对照2组比较,差异无统计学意义(P0.05)。(2)早发型与晚发型PE组血清hs-CRP高于同期对照组,差异均有统计学意义(P0.05);早发型组与晚发型组比较,差异无统计学意义(P0.05)。(3)早发型与晚发型PE组的血清MPO、hs-CRP水平与新生儿出生体重均呈负相关(P0.05);对照组则与新生儿出生体重无明显相关性(P0.05)。结论:血清MPO、hs-CRP可能在PE的病理生理过程中发挥作用。重度PE患者血清MPO、hs-CRP水平升高可引起新生儿体重下降,其机制可能与胎儿宫内生长发育有关。  相似文献   

8.
9.
OBJECTIVE: The aim of this study was to measure maternal plasma vascular endothelial growth factor concentrations during normal and hypertensive pregnancies and examine their relationship with maternal total peripheral resistance values. STUDY DESIGN: Plasma concentrations of total immunoreactive vascular endothelial growth factor and total peripheral resistances were measured serially throughout pregnancy in 20 women with preeclampsia, 24 women with gestational hypertension, and 26 normotensive control women. One-way analysis of variance and a regression model were used to analyze the vascular endothelial growth factor levels in the groups and the relationship between vascular endothelial growth factor concentration and total peripheral resistance. RESULTS: At 10 to 14 weeks' gestation plasma vascular endothelial growth factor concentrations in all subjects were 4 to 5 times greater than the levels measured post partum (P <.0001). Mean vascular endothelial growth factor concentrations were similar in the control and gestational hypertension groups; in both groups levels remained stable until 34 to 36 weeks' gestation, when levels increased a further 1.3-fold (P <.01). In comparison, vascular endothelial growth factor concentrations in subjects in the preeclampsia group were greater at 28 to 32 weeks' gestation (P =.002) and at 34 to 36 weeks' gestation (P <.001). Vascular endothelial growth factor concentrations were also increased during the 4 weeks that preceded the diagnosis of preeclampsia (P <.05). Vascular endothelial growth factor concentrations were associated with the elevated total peripheral resistance observed during the clinical disorder in the preeclampsia group but not in the other groups. CONCLUSION: Maternal plasma vascular endothelial growth factor concentrations increased before the clinical onset of preeclampsia and were further elevated during the vasoconstricted state observed in this disorder. We speculate that the hyperdynamic circulation that characterizes the latent phase of preeclampsia causes vascular shear stress, which in turn increases the levels of circulating vascular endothelial growth factor. Because vascular endothelial growth factor normally acts as a vasodilator, its increase may represent an unsuccessful vascular rescue response.  相似文献   

10.
《Seminars in perinatology》2014,38(3):167-176
Ischemic placental disease is a recently coined term that describes the vascular insufficiency now believed to be an important etiologic factor in preeclampsia, intrauterine fetal growth restriction, and placental abruption. Given the increased risk for poor maternal and fetal outcomes, early prediction and prevention of this disorder is of significant clinical interest for many. In this article, we review the second- and third-trimester serum and ultrasound markers predictive of ischemic placental disease. Limited first-trimester data is also presented. While current studies report a statistical association between marker levels and various adverse perinatal outcomes, the observed diagnostic accuracy is below the threshold required for clinical utility. An exception to this generalization is uterine artery Doppler for the prediction of early-onset preeclampsia. Metabolomics is a relatively new analytic platform that holds promise as a first-trimester marker for the prediction of both early- and late-onset preeclampsia.  相似文献   

11.
早发型重度子癎前期的临床特点和治疗探讨   总被引:2,自引:0,他引:2  
目的探讨早发型重度子癎前期的临床特点及治疗。方法对温州医学院附属第一医院妇产科2002-01-2004-12收治的179例重度子癎前期患者(其中早发型43例,即24~34孕周发病者;晚发型136例,即≥34孕周发病者)及其新生儿210例进行回顾性分析,观察指标包括一般情况、并发症/合并症及母婴结局。结果早发型重度子癎前期患者分娩孕周较晚发型早(P<0·01)、治疗时间较晚发型长(P<0·05),其临床症状及并发症/合并症较晚发型严重,母婴结局明显较晚发型差。结论早发型重度子癎前期病情严重,围生儿预后不佳,应根据母胎情况,严格选择病例进行保守治疗,同时密切监测母胎病情变化。  相似文献   

12.
OBJECTIVE: To investigate the differences in the expression of intercellular adhesion molecule-1 (ICAM-1) in the placenta and the concentration of soluble ICAM-1 between early-onset and late-onset preeclampsia. METHODS: Preeclampsia was divided into early-onset type (EO: 20 to 31 weeks gestation) and late-onset type (LO: > or = 32 weeks gestation). Post delivery, placentas were obtained from 19 control pregnant women and from 9 EO and 8 LO preeclamptic women. The expression of ICAM-1 in placenta was determined by immunohistochemical staining. Blood samples were taken from 21 non-pregnant women, 16 control pregnant women, 13 EO and 8 LO preeclamptic women, and umbilical cord blood samples from 38 control pregnancies and from 16 EO and 14 LO preeclampsia. The concentration of ICAM-1 was measured by enzyme-linked immunosorbent assays. RESULTS: The expression of ICAM-1 in placenta was higher in LO than in EO preeclampsia (48.2 +/- 8.2% vs 17.9 +/- 5.0%) (p < 0.05). ICAM-1 concentration in umbilical cord blood was higher in EO than in LO preeclampsia (umbilical artery, 150.6 +/- 34.0 ng/ml vs 90.3 +/- 9.4 ng/ ml) (umbilical vein, 128.3 +/- 31.2 ng/ml vs 91.3 +/- 10.2 ng/ml) (p < 0.05). CONCLUSIONS: Significant differences were noted in the expression of ICAM-1 between patients with EO and LO preeclampsia, which suggest that the possibility that EO and LO preeclampsia may have different onset mechanisms.  相似文献   

13.
Objectives. To evaluate soluble endoglin (sEng) and the soluble fms-like tyrosine kinase 1 (sFlt1) to placental growth factor (PlGF) ratio for the prediction of preeclampsia in high-risk women, and to evaluate differences in sEng between women with high-risk singleton and multiple gestation pregnancies. Study Design. We collected serial serum specimens from 119 women at high preeclampsia risk. sEng, sFlt1 and PlGF were measured by ELISA. Results. Among subjects who did not develop preeclampsia, mean serum sEng was significantly higher in those with multiple gestation pregnancies vs. high-risk singletons. Among women with singleton gestations, mean serum sEng was higher in subjects who developed early-onset (<34 weeks) and late-onset (≥ 34 weeks) preeclampsia, as compared with subjects without preeclampsia, from 22 weeks and 28 weeks gestation onward, respectively. The within-woman rate of change of sEng was also higher in women who later developed preeclampsia. Conclusions. sEng is higher in women with multiple gestations vs. high-risk singleton pregnancies. In high-risk women, serum sEng is increased prior to preeclampsia onset.  相似文献   

14.
BACKGROUND: Preeclampsia (PE) is more common at high than low altitude and contributes to the altitude-related decline in birth weight. Since inflammatory markers are implicated in PE, we asked if such markers differed in PE vs. normotensive pregnant (NORM) women residing at high altitude (3600-4100 m), and were related to uterine artery blood flow (UA BF) or fetal growth. METHODS: Subjects were 33 Andean pregnant residents of Bolivia, comprising six with early-onset PE (≤ 34 wk), 12 with late-onset PE (> 34 wk), and 15 gestational-age matched NORM. Maternal pro- and anti-inflammatory cytokines were measured using a multiplex bead-based assay and UA BF by Doppler ultrasound. RESULTS: PE compared to NORM women had higher levels of the pro-inflammatory cytokines IL-6 and IL-8 as well as higher levels of the anti-inflammatory cytokine IL-1ra, but only IL-6 levels were higher when gestational age was controlled. Women with early- vs. late-onset PE had higher TNFα levels, and higher IL-6 was negatively correlated with birth weight in all women at ≤ 34 wk. We suggest that pro-inflammatory factors influence both the timing and severity of PE at high altitude.  相似文献   

15.
Purpose: We aimed to compare the serum autotaxin levels in early- and late- preeclamptic and healthy pregnant patients at a university hospital.

Methods: A total of 55 singleton preeclamptic women who delivered at Cerrahpasa Medical Faculty were included in the study. The patients were subdivided into two groups: early-onset preeclampsia (n = 31) and late-onset preeclampsia (n = 24). Demographic and clinical data were compared between early-onset and late-onset preeclamptic patients. The control group was composed of 32 healthy pregnant patients.

Results: The mean autotaxin levels were 1.16 ± 0.97 and 0.7 ± 0.35 ng/ml in the early- and late-onset preeclampsia groups, respectively. Autotaxin levels were significantly higher in early-onset preeclampsia group compared with late-onset preeclampsia group. Autotaxin levels were found to be significantly higher in preeclamptic patients compared with control group. Serum autotaxin levels showed a significant positive correlation with maternal systolic, diastolic blood pressures and uric acid levels.

Conclusion: Autotaxin might be a promising marker for detecting early-onset preeclampsia. However, further studies are necessary to confirm this hypothesis.  相似文献   

16.

Background

The main purpose of this study was to determine the maternal and umbilical cord blood oxidized LDL (oxLDL) and soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) levels in early- and late-onset preeclampsia (PE).

Materials and methods

A case–control study was conducted in pregnant women with early-onset (before 34 weeks’ gestation n = 19) and late-onset (after 34 weeks’ gestation n = 22) PE compared to healthy normotensive pregnant controls (n = 44). Groups were compared for the maternal and umbilical cord plasma oxLDL and serum sLOX-1 levels.

Results

The mean maternal and umbilical cord serum sLOX-1 and plasma oxLDL levels were significantly increased in early- and late-onset PE compared to controls (p < 0.001). When early- and late-onset PE women were compared with serum sLOX-1 levels, the increase was more pronounced in early PE (p < 0.001). However, same comparison is not statistically significant in cord blood for oxLDL where as it is significantly higher in maternal blood for oxLDL in early-onset PE group. Maternal and cord blood oxLDL and sLOX-1 levels are positively correlated with each other; however, they are negatively correlated with fetal weight and gestational age.

Conclusions

According to our results, maternal and umbilical cord blood levels of oxLDL and sLOX-1 were higher in preeclamptic pregnant. Thus, for the first time it has been shown that oxLDL and sLOX-1 levels were higher in fetal circulation as well as plasma of preeclamptic pregnant. However, sLOX-1 levels seem to be more implying than oxLDL for the differentiation of early and late preeclampsia.  相似文献   

17.
INTRODUCTION: Elevations in circulatory DNA, as measured by real-time PCR, have been observed in pregnancies with manifest preeclampsia. Recent reports have indicated that circulatory nucleosome levels are elevated in the periphery of cancer patients. We have now examined whether circulatory nucleosome levels are similarly elevated in cases with preeclampsia. METHODS: Maternal plasma samples were prepared from 17 cases with early onset preeclampsia (<34 weeks gestation) with 14 matched normotensive controls, as well as 15 cases late-onset preeclampsia (>34 weeks gestation) with 10 matched normotensive controls. Levels of circulatory nucleosomes were quantified by commercial ELISA (enzyme-linked immunosorbant assay). RESULTS: The level of circulatory nucleosomes was significantly elevated in both study preeclampsia groups, compared to the matched normotensive control group (p = 0.000 and p = 0.001, respectively). CONCLUSIONS: Our data suggests that preeclampsia is associated with the elevated presence of circulatory nucleosomes, and that this phenomenon occurs in both early- and late-onset forms of the disorder.  相似文献   

18.
Objective: The purpose of this study was to evaluate the association of vascular endothelial dysfunction with increased oxidant generation in the metabolism of hypoxanthine to uric acid in early-onset compared to late-onset preeclampsia. Methods: We investigated 12 women with early-onset preeclampsia, 14 women with late-onset preeclampsia, and 20 women with uncomplicated pregnancies. We measured serum derivatives of reactive oxygen metabolites (d-ROMs) as a marker of oxygen free radicals, serum biological antioxidant potential (BAP), hypoxanthine, uric acid, uric acid clearance (CUA), and flow-mediated vasodilation (FMD) as a marker of endothelial function in preeclamptic women. Results: Concentration of d-ROMs was significantly higher in both preeclamptic groups compared to the control group. Plasma levels of uric acid were significantly elevated in both preeclamptic groups compared to the control group. Plasma levels of hypoxanthine were significantly higher in early-onset preeclamptic women compared to controls, but not in late-onset preeclamptic women. CUA was significantly lower in late-onset preeclamptic women compared to controls, but not in early-onset preeclamptic women. The concentrations of hypoxanthine and uric acid correlated positively with the concentration of d-ROMs in all pregnant women. FMD was significantly lower in both preeclamptic groups compared with controls, but FMD in the early-onset preeclamptic group was significantly lower than in the late-onset preeclamptic group. Conclusions: We found that increased oxidant generation during metabolism of hypoxanthine to uric acid may impair endothelial function in early-onset preeclampsia.  相似文献   

19.
20.
Preeclampsia is a hypertensive disorder unique to pregnancy. Although the pathogenesis of the disease begins with aberrant spiral artery invasion in the first trimester, clinical symptoms usually do not present until late in pregnancy. Apolipoprotein CII (ApoCII) and its negative regulator, apolipoprotein CIII (ApoCIII), have recently been described as atherogenesis biomarkers in models of cardiovascular disease. Given the similarities in pathology, etiology, and clinical presentation between cardiovascular disease and preeclampsia, we hypothesized that the ratio of ApoCIII to ApoCII in maternal first trimester plasma would predict preeclampsia later in pregnancy. To test this hypothesis, plasma was prospectively collected from 311 nulliparas at 8 to 12 weeks gestation. After delivery, patients were divided into cohorts based on preeclampsia diagnosis. Conditioning monocytes with preeclamptic plasma potentiated monocyte adhesion to endothelial cells in an in vitro model. The ratio of ApoCIII to ApoCII was significantly elevated in patients with severe preeclampsia relative to normotensive and gestational hypertensive individuals (P < .05) as determined by mass spectrometry and competitive enzyme-linked immunosorbent assay (ELISA) assays. These results support a predictive change in the ratio of ApoCIII to ApoCII in pregnancies complicated by severe preeclampsia.  相似文献   

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