血清尿酸水平与妊娠期高血压疾病的关系

妊娠期高血压疾病(HDCP)是一种较为常见的严重危害母婴健康的妊娠期特有疾病,其病因及发病机制尚不明确。HDCP主要病理生理是全身小动脉痉挛,内皮损伤和局部缺血。血清尿酸(UA)是人类嘌呤代谢的最终产物,主要由肾脏排泄。研究证实,HDCP与血清UA关系密切,且两者相互作用、相互影响。监测血清UA对于评估HDCP尤其是子痫前期的发生与发展可能具有重要意义。但临床上应用血清UA水平预测或早期诊断子痫前期仍存在争议;联合多种检测指标,构建新的检测模型,是否可有效提高预测价值,目前尚未明确。主要围绕HDCP的基本病理生理与血清UA代谢的相互影响,血清UA与子痫前期发病的密切关系,血清UA对子痫前期临床诊断、母儿预后的预测价值等方面进行综述。     

重度子痫前期患者的血浆代谢组学研究

目的:探讨重度子痫前期患者血浆的代谢组变化及代谢组学技术早期诊断重度子痫前期的应用价值.方法:采用基于高效液相色谱-3200 Q trap质谱的代谢组学方法,检测51例重度子痫前期患者和45例正常妊娠妇女血浆代谢组的变化,运用模式识别方法分析数据.结果:51例重度子痫前期患者和45例正常妊娠妇女经代谢组学方法得到很好的区分,并找到相对应的16个潜在的生物标记物,其中浓度呈下降趋势的代谢小分子有峰89、95、98、118、135、157、187、191、215、240,浓度呈上升趋势的有峰139、155、284、451、837、922.结论:建立的代谢组学方法可以区分重度子痫前期和正常妊娠,综合代谢标记物变化趋势构成重度子痫前期的代谢特征,其对早期诊断重度子痫前期有很好的前景.     

尿蛋白在子痫前期诊断中的价值

子痫前期是严重威胁母胎生命的妊娠期特发性疾病,而尿蛋白在子痫前期的预测及诊断价值尚未明确统一,不仅如此,近几年来一部分国家的组织或机构对原有指南进行了更新,最突出的改变即为调整了尿蛋白的诊断地位。结合国内外不同国家的机构或组织发布的子痫前期指南及近几年来最新研究进展,针对尿蛋白在诊断过程中存在的争议点及尿蛋白对于子痫前期的意义作综述,发现尿蛋白在子痫前期诊断中存在一定的价值。不仅如此,重视并积极处理尿蛋白可减少并发症的产生,有利于降低孕产妇不良妊娠结局发生率及相应的医疗资源及经济资源。     

血浆D-二聚体与子痫前期关系的研究进展

子痫前期是一种妊娠期特发性疾病,是导致围产期母儿不良结局的主要原因。目前,子痫前期的发病机制尚不完全清楚,但已证实其基本病理生理变化是全身小血管痉挛及血管内皮细胞受损。血浆D-二聚体(D-D)作为一种纤维蛋白降解产物,可反映凝血和纤溶系统的激活状态,系血栓形成活性的间接标记。近来绝大多数研究认为子痫前期患者血浆D-D水平较正常妊娠者高,其水平与子痫前期病情严重程度可能呈正相关,血浆D-D对子痫前期及其并发症有一定的预测价值,血浆D-D联合其他指标[如:可溶性血管内皮生长因子受体-1(sFlt-1)、胎盘生长因子(PLGF)等]可增加其预测效率。但目前仍存在部分相反的研究结论,故需要大量高质量的前瞻性队列研究来进一步探讨和证实血浆D-D在评估子痫前期病情程度及预测子痫前期的价值,为血浆D-D应用于子痫前期的病情监测和预测提供参考依据。     

子痫前期与遗传易感基因多态性的研究进展

子痫前期是一种严重影响母婴健康的疾病,确切发病机制至今不明,遗传易感因素在其发病中发挥了举足轻重的作用,凝血与纤溶异常、胎盘发育障碍、氧化应激、脂质代谢异常及炎症因子等相关基因的多态性均与子痫前期的发病密切相关;印迹基因在子痫前期的发病中也发挥着重要作用。明确子痫前期的遗传发病机制,可为疾病的预测、预防、治疗提供新的方向和思路。     

缺氧对重度子痫前期患者胎盘绒毛组织代谢足迹变化的影响

目的:探讨在不同氧浓度下体外培养正常妊娠孕妇及重度子痫前期患者胎盘绒毛组织培养液中代谢足迹的变化。方法:选择正常妊娠组(27例)及重度子痫前期组(27例)孕妇,在胎盘边缘、中间、近脐带处取绒毛组织,分别在1%氧浓度下及6%氧浓度下培养96小时,采用高效液相质谱色谱仪检测培养液中代谢产物,观察不同氧浓度下培养的绒毛组织代谢足迹的变化。结果:两组分别取自1%氧浓度和6%氧浓度下培养的同一胎盘边缘、中间、近脐带3点处胎盘绒毛组织代谢足迹的比较差异无统计学意义(P>0.05);1%氧浓度与6%氧浓度下培养的正常妊娠组胎盘绒毛组织代谢足迹比较,发现545个代谢物差异有统计学意义(P<0.05);1%氧浓度与6%氧浓度下培养的重度子痫前期组胎盘绒毛组织代谢足迹的比较差异无统计学意义(P>0.05),1%氧浓度下培养的正常妊娠组与6%氧浓度下培养的重度子痫前期组胎盘绒毛组织代谢足迹的比较差异无统计学意义(P>0.05)。结论:缺氧可能影响胎盘绒毛组织的代谢,在重度子痫前期的发病机制中起重要作用,而利用高效液相质谱色谱仪的代谢组学技术能测定在不同氧浓度下培养的正常妊娠组和重度子痫前期孕妇胎盘绒毛组织代谢足迹的变化,表明该方法适合于重度子痫前期的代谢组学研究。     

生物学标记结合临床风险推动子痫前期预测更上一层楼

也许苦于对子痫前期的病因及发病机制的不甚清楚,子痫前期的预测虽是学者们花费精力最大的研究课题之一,但仍是一些教科书中文字精简到少而不能再少的部分.相对于以预防为主的现代医学,子痫前期发病的预测和早期诊断当属临床最关键环节之一.     

血浆可溶性血管内皮生长因子受体1水平变化对子痫前期发病的早期预测价值

目的 探讨孕妇血浆中可溶性血管内皮生长因子受体1(sFlt-1)水平变化对子痫前期发病的早期预测价值.方法 采用前瞻性研究方法,应用酶联免疫吸附试验(ELISA)对146例妊娠20～26周最初血压正常孕妇的血浆中sFlt-1水平进行测定,并随访观察孕妇血压变化和妊娠结局.结果 (1)146例孕妇中,发展为子痫前期患者12例(子痫前期组),余134例孕妇妊娠结局正常(正常妊娠组).(2)子痫前期组孕妇血浆sFlt-1水平为(4135±699)ng/L,正常妊娠组为(1490±1033)ng/L,两组比较,差异有统计学意义(P＜0.01).子痫前期组患者临床诊断前10周即出现sFlt-1水平升高.(3)sFlt-1水平预测子痫前期,受试者工作曲线的曲线下面积为0.981.以sFlt-1≥3344 ng/L为切点,预测子痫前期的敏感度、特异度、阳性预测值及阴性预测值分别为100%、96%、67%、100%.结论 子痫前期患者血浆sFlt-1水平升高的变化早于临床诊断子痫前期10周以上,因此,血浆sFlt-1水平变化可作为子痫前期发病的早期预测指标.     

基于生化指标的重度子痫前期辅助诊断模型构建

目的:构建妊娠女性重度子痫前期的辅助诊断模型，并建立个体诊断重度子痫前期的列线图。方法:回顾性分析2017年1月至2019年12月在安徽省妇幼保健院妇产科住院分娩的16387例孕妇病历资料，按是否发生重度子痫前期，分为重度子痫前期组(n=192)和非重度子痫前期组(n=16195)。对两组临床特征和生化指标等各项因素进行单因素比较，采用多因素Logistic回归分析重度子痫前期的危险因素并建立诊断模型，应用R语言软件中回归建模策略程序包建立诊断的列线图模型，采用受试者工作特征(ROC)曲线分析列线图模型对重度子痫前期的诊断效率。结果:Logistic回归分析发现，胎儿生长受限以及生化指标中尿酸、磷、同型半胱氨酸、天门冬氨酸氨基转移酶、甘油三酯、乳酸脱氢酶是重度子痫前期的危险因素(OR>1,P<0.001);白蛋白、钙是重度子痫前期的保护因素(OR<1,P<0.001)。根据多因素Logistic回归分析筛选出来的9个预测变量，建立辅助诊断重度子痫前期的列线图。ROC曲线显示列线图模型诊断重度子痫前期的AUC为0.891,最佳阀值为0.016,预测敏感度与特异度分...     

子痫前期预测指标的筛选及应用价值

目的:筛选简便且实用的预测子痫前期的临床指标,并探讨这些指标预测子痫前期的应用价值。方法:回顾分析子痫前期患者危险因素,包括孕妇年龄、高血压家族史、流产史、孕产次、子痫前期史、工作种类及孕期水肿的发生,统计各指标与子痫前期发生的相互关系。结果:5项为子痫前期的高危因素,分别为:年龄≥35岁,高血压家族史,子痫前期史,经产妇,重体力劳动者。其中,子痫前期史结合水肿症状预测子痫前期,敏感性最高(50.0%),特异度达100%。结论:临床上可使用筛选出的指标,结合水肿症状预测,从而在亚临床阶段进行干预,减少重度子痫前期的发病率或控制在轻症阶段。     

子痫前期孕妇血清代谢组学分析

目的:比较妊娠子痫前期(PE)患者分娩前后血清代谢轮廓的变化,建立疾病区分模型并筛选出具有潜在临床应用价值的特征代谢物。方法:选取2017年9月-2018年3月天津市第三中心医院收入院的孕妇共45例,其中PE患者(PE组)20例,正常孕妇(对照组)25例,应用超高效液相色谱与质谱联用仪(UPLC-MS)分别检测PE组孕妇分娩前、分娩后以及对照组的血清标本,筛选出差异性特征代谢物并进行分析。结果:构建了妊娠PE组血清代谢轮廓模型,共筛选出溶血磷脂酰胆碱类物质LPC 18:0、LPC 22:6、14-甲基十六烷酸、二十二酸和1,25-二羟基维生素D3-26,23内酯共5种差异性代谢产物,且溶血磷脂酰胆碱类物质LPC 18:0、LPC 22:6和14-甲基十六烷酸3种物质在PE分娩前与分娩后的差异有统计学意义(均P<0.05)。结论:构建代谢轮廓模型具有很强地区分PE患者分娩前后及正常孕妇的能力,筛选出特征代谢物能够反映PE患者代谢水平的变化趋势,为PE的预测、诊治提供参考。     

可溶性血管内皮生长因子受体-1与胎盘生长因子在子痫前期

归纳子痫前期的病理生理过程以及可溶性血管内皮生长因子受体-l（sFlt-1）、胎盘生长因子（PLGF）与子痫前期的研究情况,PLGF是血管内皮生长因子（VEGF）家族成员之一,PLGF与Flt-1受体结合时,发挥促血管生成和促绒毛滋养细胞增殖、浸润的效应,而这些生物学功能均可被sFlt-1阻断,且sFlt-1对PLGF具有强效的拮抗作用,调节PLGF的功能。在子痫前期妊娠妇女血清中sFlt-1的水平升高,早于疾病的发生。子痫前期患者血浆中PLGF的水平降低。总结sFlt-1、PLGF预测诊断子痫前期发生及病情严重程度的研究进展,探讨sFlt-1、PLGF在子痫前期临床诊断中的意义。     

Early detection of pre-eclampsia within the scope of prenatal care

Pregnancy-induced hypertension and preeclampsia account for about 25% of perinatal morbidity and mortality and are a leading cause of maternal death in developed countries. Consequently, early diagnosis of the disease seems very important. Numerous clinical and biochemical methods have been described and tested for the prediction of preeclampsia. The results of these studies are critically described here. In summary, no test presently available serve as a reliable early marker of developing preeclampsia. However, vaginal Dopplerultrasound may allow prediction as early as the 12th to 16th week of gestation. Moreover, methods detecting underlying mechanisms of the disease such as endothelial dysfunction and platelet activation, are being developed and might provide improved early identification of pregnant women at high risk.     

Placental Growth Factor and Soluble,Fms-Like Tyrosine Kinase-1 in Preeclampsia: A Case-Cohort (PEARL) Study

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.     

Preeclampsia and the Anti-Angiogenic State

Preeclampsia is a major cause of maternal and fetal morbidity and mortality worldwide, however, its etiology remains unclear. Abnormal placental angiogenesis during pregnancy resulting from high levels of anti-angiogenic factors, soluble Flt1 (sFlt1) and soluble endoglin (sEng), has been implicated in preeclampsia pathogenesis. Accumulating evidence also points to a role for these anti-angiogenic proteins as serum biomarkers for the clinical diagnosis and prediction of preeclampsia. Uncovering the mechanisms of altered angiogenic factors in preeclampsia may also provide insights into novel preventive and therapeutic options.     

降低子痫前期患者严重并发症的策略

妊娠期高血压疾病是妊娠最常见的并发症之一,尤其是临床表现严重的子痫前期、子痫和HELLP综合征,可使母亲与胎儿的发病率和死亡率增加,如何及时、准确地诊断和处理关系到患者病情的进展和预后。本文从风险预测、诊断标准和处理原则几个方面阐述了降低子痫前期患者严重并发症发生的策略,以期最大程度改善妊娠期高血压疾病患者的母儿预后。     

Early second-trimester plasma levels of NT-proBNP in women who subsequently develop early-onset preeclampsia

Plasma levels of NT-proBNP are elevated in women with preeclampsia at the time of diagnosis. The objective of this case-control study was to evaluate N-terminal proBNP (NT-proBNP) in maternal plasma as an early second-trimester biomarker for prediction of early-onset preeclampsia. In early second-trimester samples, women who later developed preeclampsia at gestational age 34 wk?+?0 or earlier (n?=?16) had similar plasma levels of NT-proBNP (median 51.8, range 26.1–131.9?pg/ml) as women with uncomplicated pregnancy outcomes (n?=?43) (53.0, 14.9–184.2?pg/ml). The early second-trimester level of NT-proBNP cannot therefore be used as a predictive biomarker of early-onset preeclampsia.     

A prediction model for superimposed preeclampsia in women with chronic hypertension during pregnancy

OBJECTIVE: Women with chronic hypertension are at increased risk for superimposed preeclampsia. We developed a prediction algorithm for superimposed preeclampsia using clinical and laboratory information that were measured early in pregnancy. STUDY DESIGN: A secondary analysis of data that were collected from 110 women with chronic hypertension who were enrolled in a trial of calcium supplementation was performed. Blood pressure, the renin-angiotensin system, and calcium metabolism were assessed at 12, 20, 28, and 36 weeks of gestation and 6 weeks after delivery. Multivariable logistic regression was used to develop the predictive model. RESULTS: Thirty-seven women had superimposed preeclampsia. The final model included systolic blood pressure, serum uric acid, and plasma renin activity, which were all measured at 20 weeks of gestation. Women with high systolic blood pressure (>140 mm Hg), elevated uric acid (>3.6 mg/dL), and low plasma renin activity (<4 ng/mL/hr) had an 86% probability of having superimposed preeclampsia. Women with 2 risk factors had a 62% probability of superimposed preeclampsia, and women with only 1 risk factor had a 30% to 40% probability of superimposed preeclampsia. CONCLUSION: We developed a prediction algorithm that can be validated in future studies for superimposed preeclampsia for women with chronic hypertension.     

Serum concentrations of CA-125 in normal and preeclamptic pregnancies

Aim  

The present prospective study aims to investigate the serum concentrations of CA-125 in normal and preeclamptic pregnancies and thus to specify the clinical utility of this biochemical marker in prediction, diagnosis and follow up of preeclampsia.     

Augmented oxidative stress as well as antioxidant capacity in maternal circulation in preeclampsia

OBJECTIVES: Isoprostanes are stable markers of oxidative stress. We wanted to assess maternal circulating levels of total 8-isoprostane and indices of antioxidant capacity in preeclampsia compared to uneventful pregnancies. STUDY DESIGN: Total 8-isoprostane concentrations, FRAP (ferric reducing ability of plasma), Vitamin E and d-ROM (diacron reactive oxygen metabolites) were measured in maternal venous blood samples from preeclamptic (n=21) and uncomplicated (n=38) pregnancies at cesarean section. RESULTS: Median total 8-isoprostane concentration was elevated in preeclampsia compared to uncomplicated pregnancies (354 and 218 pg/mL, P=0.02). Median FRAP level was also elevated in preeclampsia compared to uncomplicated pregnancies, but to a lesser degree than 8-isoprostane. A positive correlation between 8-isoprostane and previously analyzed placenta-derived sFlt1 (soluble fms-like tyrosine kinase 1) levels in the maternal circulation was found in preeclampsia. CONCLUSION: We found a relative more increase for the oxidative stress marker (8-isoprostane) than for the antioxidant capacity (FRAP) in preeclampsia compared to uneventful pregnancies.