sFlt-1与子痫前期患者围生结局相关性的研究
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摘要
子痫前期的病理复杂：遗传基因、免疫、环境因素等相互作用。目前认为子痫前期的发展主要分为两个阶段.第一阶段是无临床症状期。其主要特点是孕早期胎盘发育异常导致胎盘缺血、缺氧并释放过量的胎盘物质入母血循环。如此导致第二阶段的出现即临床症状期。在第二阶段患者出现高血压、肾损害、蛋白尿甚至HELLP综合征(溶血、肝酶升高、血小板降低)、子痫、及其他器官损害。其病理改变的核心是血管内皮细胞功能紊乱。本研究将从三方面探讨导致子痫前期患者血管内皮功能异常的机制及其与临床结局的关系。1胎盘血管因子VEGF、PIGF、sFlt-1、Flt-1mRNA表达与子痫前期的关系。2母体外周血sFlt-1水平的异常与子痫前期的关系,以及与围产结局的相关性。3、产后恢复与孕期母体外周血sFlt-1水平的相关性。
第一部分：、胎盘VEGF、PIGF、Flt-1、sFlt-1mRNA的表达与子痫前期的相关性
目的：胎盘组织血管内皮生长因子(VEGF)胎盘生长因子(PIGF)及其血管内皮生长因子受体1(VEGFR1, Flt-1).可溶性血管内皮生长因子受体1(sVEGFR1, sFlt-1) mRNA的表达与子痫前期发病的关系。
方法：天津市第一中心医院产科住院分娩的90例产妇。其中45例健康产妇为对照组,平均年龄(26.30±2.20)孕周(37.41±2.47)。子痫前期患者45例为试验组；平均年龄(27.70±2.60)孕周(35.44±0.86)。其中重度25例,轻度20例。反转录-聚合酶链反应(RT-PCR)方法检测胎盘组织中VEGF、PIGF、Flt-1、sFlt-1mRNA的表达。
结果：子痫前期组胎盘组织VEGF、PLGF、Flt-1、sFlt-1mRNA的相对表达量均高于对照组,(分别是4.05±0.39,2.970±0.35,3.48±0.73,0.60±0.09 vs 1.38±0.36 1.03±0.37,1.51±0.76,,0.14±0.26)差别具有显著性,(P<0.01)。
结论：胎盘组织sFlt-1mRNA的高表达与子痫前期妇女内皮损伤、高血压和蛋白尿的出现有密切关系。
第二部分、子痫前期患者与正常孕妇外周血中sFlt-1水平的差异。
目的：1、通过比较孕妇外周血中sFlt-1水平在子痫前期患者与正常孕妇间的差异,了解sFlt-1对子痫前期发病的影响。2.、分析外周血sFlt水平与疾病严重程度的关系。
方法：60例子痫前期重度患者,30例子痫前期轻度,30例正常孕妇。比较三组孕妇一般情况及外周血sFlt-1浓度差异、孕周以及新生儿体重。
结果：1、重度子痫前期患者、轻度子痫前期患者及正常孕妇对照组三组sFlt-1浓度有显著性差异(P<0.01)。子痫前期重度组最高,子痫前期轻度次之。2、三组孕周有显著差异(P<0.01)。3、新生儿体重重度组小于轻度和对照组(P<0.01),轻度组和对照组无显著差异(P>0.05)。
结论：子痫前期外周血sFlt-1水平显著高于正常孕妇,sFlt-1水平与疾病的程度有关。
第三部分重度子痫前期早发型和晚发型的基本情况、临床指标、妊娠结局与sFlt-1的关系
目的：分析早发型重度子痫前期与晚发型重度子痫前期的差异,以及sFlt-1与临床指标的关系,探讨早发型中断妊娠的时机。
方法：研究60例重度子痫前期患者,并将其分为早发型和晚发型(以34周为界),对两组并发症,临床实验室指标,围产儿结局的差异进行统计学分析。结果：早发型重度子痫前期合并慢性高血压高、妊娠期糖尿病的比例高。新生儿小于胎龄儿比例高。实验室检查肝酶高于晚发组。两组sFlt-1的浓度无显著差异。sFlt-1与24h尿蛋白、血压、脐血流S/D呈正相关性；在早发型中sFlt-1与血尿酸有正相关性,与新生儿体重有负相关性,而在晚发型中无明显相关性。
结论：1、早发型重度子痫前期患者和晚发型患者可能存在着发病机制差异。
2、高水平的sFlt-1是造成新生儿低体重、血压升高、尿蛋白的关键因素。密切监测sFlt-1水平有助于选择最佳的中断妊娠时机。
第四部分：重度子痫前期患者产后恢复与孕期sFlt-1水平的关系
有10例重度子痫前期患者回访,分析病例得出结果,子痫前期患者产后的恢复不同,有患者产后半年仍有高血压、蛋白尿。分娩后持续蛋白尿、高血压与分娩前高水平的sFlt-1有关。孕期高水平sFlt-1可能造成日后的心血管疾患。
The pathogenesis of preeclampsia is complex; numerous genetic, immunologic, and environmental factors interact. It has been suggested that preeclampsia is a two-stage disease, he first stage is asymptomatic, characterized by abnormal placental development during the first trimester resulting in placental insufficiency and the release of excessive amounts of placental materials into the maternal circulation. This in turn leads to the second, symptomatic stage, wherein the pregnant woman develops characteristic hypertension, renal impairment, and proteinuria and is at risk for the HELLP syndrome (hemolysis, elevated liver function enzymes and low platelets), eclampsia, and other end-organ damage. Its core is the pathological changes of vascular endothelial cell dysfunction.Discussion on the three aspects of this research from causing mechanism of Vascular Endothelial dysfunction in patients with preeclampsia and its relationship with clinical outcomes. 1、Placental vascular factor expression of VEGF, PIGF, sFlt-1, Flt-1 and the relationship between preeclampsia2、Abnormal maternal peripheral blood levels of sFlt-1 and the relationship between preeclampsia and correlation with perinatal outcomes.3、The relationship between postpartum recovery and sFlt-1 level in maternal peripheral blood during pregnancy.
Part 1:Placental expression of VEGF, PIGF, Flt-1, sFlt-1mRNA and correlation of preeclampsia
Objective:Placental vascular endothelial growth factor (VEGF) placenta growth factor (PIGF) and vascular endothelial growth factor receptor 1 (VEGFR1, Flt-1), soluble vascular endothelial growth factor receptor 1 (sVEGFR1,sFlt-1) of the mRNA expression and relationship between preeclampsia. Method:90 pregnant women giving birth in the obstetric department of Tianjin first Central Hospital.45 cases of maternal health is the control group, the average age (26.3±2.2) gestation weeks (37.41±2.47). For the Group of 45 cases of patients with preeclampsia; average age (27.7±2.6) weeks (35.44±0.86) severe 25 cases, mild 20 cases. Reverse transcription-polymerase chain reaction (RT-PCR) methods for detection of placental tissue in the expression of VEGF and PLGF, Flt-1, sFlt-lmRNA.Result:Preeclampsia placenta tissue VEGF and PIGF Flt-1, sFlt-1mRNA expression are higher than the control group(4.05±0.39,2.970±0.35,3.48±0.73,0.60±0.09 vs 1.38±0.36±0.37,1.51±0.76,,0.14±0.26).The difference are significant (P<0.01). Conclusion:sFlt-lmRNA high expression of placental tissue and endothelial damage in preeclampsia women closely, hypertension and proteinuria occurs.
Part 2:SFlt-1 concentration in peripheral blood of pregnant women with preeclampsia relationship between perinatal outcomes.
Objective:1.By comparing the sFlt.-1 concentrations in maternal peripheral blood in patients with preeclampsia and normal differences between pregnant women, understand the impact of sFlt-1 on the pathogenesis of preeclampsia.2. Analysis of peripheral blood concentration of sFlt and correlation of adverse pregnancy outcomes. Method:60 cases of severe preeclampsia patients,30 cases of mild preeclampsia,30 healthy pregnant women. Compared three groups of pregnant women in General and sFlt-1 in peripheral blood concentration differences, gestational and neonatal weight. Result:SFlt-1 there are significant differences between the three group (P＜0.01). Severe neonatal weight less than mild and control groups, mild group and control group no significant difference (P>0.05)。Conclusion:Peripheral blood of preeclampsia sFlt-1 level is significantly higher than in normal pregnant women, sFlt-1 levels and the extent of the disease concerned.
Part 3:Early onset and late onset severe pre-eclampsia's basic, clinical indicators, pregnancy outcomes and relationship sFlt-1
Objective:Analysis of early-onset severe preeclampsia and late onset severe preeclampsia of differences, as well as the relationship between sFlt-1 and clinical parameters to explore early-onset time of interruption of pregnancy.Method:Study on 60 cases of patients with severe preeclampsia, and is divided into early onset and late onset (bounded by 34 weeks), two sets of complications, clinical laboratory indicators, statistical analysis of the differences in perinatal outcomes. Result: Early-onset severe preeclampsia complicated a high proportion of gestational diabetes mellitus and chronic high blood pressure. A high proportion of newborns small for gestational age infants. Laboratory examination of liver enzyme is higher than late-onset group. No significant difference in the concentration of sFlt-1. sFlt-1 is positive correlation with 24h protein in urine, umbilical blood flow S/D and MAP. In the early-onset have positive correlation between sFlt-1 and serum uric acid in, and neonatal weight inversely correlated, and no obvious correlation in late-onset. Conclusion:Early-onset severe pre-eclampsia patients and patients with late-onset pathogenesis differences might exist.sFlt-1 is a key factors in neonatal weight, blood pressure, protein in urine. Close monitoring of sFlt-1 levels help to choose the best timing of interruption pregnancy.
Part 4:The relationship between the level of sFlt-1 during pregnancy and postpartum recovery
10 cases of severe preeclampsia return visit, the outcome of cases, patients with severe postpartum preeclampsia track.The recovery of patients with post-partum preeclampsia are different._Proteinuria and prenatal postpartum continued high levels of sFlt-1 related. Persistent proteinuria and hypertension after delivery is related with high level of sFlt-1 during pregnancy。High levels of sFlt-1 during pregnancy may cause future cardiovascular disease.
第一部分：、胎盘VEGF、PIGF、Flt-1、sFlt-1mRNA的表达与子痫前期的相关性
目的：胎盘组织血管内皮生长因子(VEGF)胎盘生长因子(PIGF)及其血管内皮生长因子受体1(VEGFR1, Flt-1).可溶性血管内皮生长因子受体1(sVEGFR1, sFlt-1) mRNA的表达与子痫前期发病的关系。
方法：天津市第一中心医院产科住院分娩的90例产妇。其中45例健康产妇为对照组,平均年龄(26.30±2.20)孕周(37.41±2.47)。子痫前期患者45例为试验组；平均年龄(27.70±2.60)孕周(35.44±0.86)。其中重度25例,轻度20例。反转录-聚合酶链反应(RT-PCR)方法检测胎盘组织中VEGF、PIGF、Flt-1、sFlt-1mRNA的表达。
结果：子痫前期组胎盘组织VEGF、PLGF、Flt-1、sFlt-1mRNA的相对表达量均高于对照组,(分别是4.05±0.39,2.970±0.35,3.48±0.73,0.60±0.09 vs 1.38±0.36 1.03±0.37,1.51±0.76,,0.14±0.26)差别具有显著性,(P<0.01)。
结论：胎盘组织sFlt-1mRNA的高表达与子痫前期妇女内皮损伤、高血压和蛋白尿的出现有密切关系。
第二部分、子痫前期患者与正常孕妇外周血中sFlt-1水平的差异。
目的：1、通过比较孕妇外周血中sFlt-1水平在子痫前期患者与正常孕妇间的差异,了解sFlt-1对子痫前期发病的影响。2.、分析外周血sFlt水平与疾病严重程度的关系。
方法：60例子痫前期重度患者,30例子痫前期轻度,30例正常孕妇。比较三组孕妇一般情况及外周血sFlt-1浓度差异、孕周以及新生儿体重。
结果：1、重度子痫前期患者、轻度子痫前期患者及正常孕妇对照组三组sFlt-1浓度有显著性差异(P<0.01)。子痫前期重度组最高,子痫前期轻度次之。2、三组孕周有显著差异(P<0.01)。3、新生儿体重重度组小于轻度和对照组(P<0.01),轻度组和对照组无显著差异(P>0.05)。
结论：子痫前期外周血sFlt-1水平显著高于正常孕妇,sFlt-1水平与疾病的程度有关。
第三部分重度子痫前期早发型和晚发型的基本情况、临床指标、妊娠结局与sFlt-1的关系
目的：分析早发型重度子痫前期与晚发型重度子痫前期的差异,以及sFlt-1与临床指标的关系,探讨早发型中断妊娠的时机。
方法：研究60例重度子痫前期患者,并将其分为早发型和晚发型(以34周为界),对两组并发症,临床实验室指标,围产儿结局的差异进行统计学分析。结果：早发型重度子痫前期合并慢性高血压高、妊娠期糖尿病的比例高。新生儿小于胎龄儿比例高。实验室检查肝酶高于晚发组。两组sFlt-1的浓度无显著差异。sFlt-1与24h尿蛋白、血压、脐血流S/D呈正相关性；在早发型中sFlt-1与血尿酸有正相关性,与新生儿体重有负相关性,而在晚发型中无明显相关性。
结论：1、早发型重度子痫前期患者和晚发型患者可能存在着发病机制差异。
2、高水平的sFlt-1是造成新生儿低体重、血压升高、尿蛋白的关键因素。密切监测sFlt-1水平有助于选择最佳的中断妊娠时机。
第四部分：重度子痫前期患者产后恢复与孕期sFlt-1水平的关系
有10例重度子痫前期患者回访,分析病例得出结果,子痫前期患者产后的恢复不同,有患者产后半年仍有高血压、蛋白尿。分娩后持续蛋白尿、高血压与分娩前高水平的sFlt-1有关。孕期高水平sFlt-1可能造成日后的心血管疾患。
The pathogenesis of preeclampsia is complex; numerous genetic, immunologic, and environmental factors interact. It has been suggested that preeclampsia is a two-stage disease, he first stage is asymptomatic, characterized by abnormal placental development during the first trimester resulting in placental insufficiency and the release of excessive amounts of placental materials into the maternal circulation. This in turn leads to the second, symptomatic stage, wherein the pregnant woman develops characteristic hypertension, renal impairment, and proteinuria and is at risk for the HELLP syndrome (hemolysis, elevated liver function enzymes and low platelets), eclampsia, and other end-organ damage. Its core is the pathological changes of vascular endothelial cell dysfunction.Discussion on the three aspects of this research from causing mechanism of Vascular Endothelial dysfunction in patients with preeclampsia and its relationship with clinical outcomes. 1、Placental vascular factor expression of VEGF, PIGF, sFlt-1, Flt-1 and the relationship between preeclampsia2、Abnormal maternal peripheral blood levels of sFlt-1 and the relationship between preeclampsia and correlation with perinatal outcomes.3、The relationship between postpartum recovery and sFlt-1 level in maternal peripheral blood during pregnancy.
Part 1:Placental expression of VEGF, PIGF, Flt-1, sFlt-1mRNA and correlation of preeclampsia
Objective:Placental vascular endothelial growth factor (VEGF) placenta growth factor (PIGF) and vascular endothelial growth factor receptor 1 (VEGFR1, Flt-1), soluble vascular endothelial growth factor receptor 1 (sVEGFR1,sFlt-1) of the mRNA expression and relationship between preeclampsia. Method:90 pregnant women giving birth in the obstetric department of Tianjin first Central Hospital.45 cases of maternal health is the control group, the average age (26.3±2.2) gestation weeks (37.41±2.47). For the Group of 45 cases of patients with preeclampsia; average age (27.7±2.6) weeks (35.44±0.86) severe 25 cases, mild 20 cases. Reverse transcription-polymerase chain reaction (RT-PCR) methods for detection of placental tissue in the expression of VEGF and PLGF, Flt-1, sFlt-lmRNA.Result:Preeclampsia placenta tissue VEGF and PIGF Flt-1, sFlt-1mRNA expression are higher than the control group(4.05±0.39,2.970±0.35,3.48±0.73,0.60±0.09 vs 1.38±0.36±0.37,1.51±0.76,,0.14±0.26).The difference are significant (P<0.01). Conclusion:sFlt-lmRNA high expression of placental tissue and endothelial damage in preeclampsia women closely, hypertension and proteinuria occurs.
Part 2:SFlt-1 concentration in peripheral blood of pregnant women with preeclampsia relationship between perinatal outcomes.
Objective:1.By comparing the sFlt.-1 concentrations in maternal peripheral blood in patients with preeclampsia and normal differences between pregnant women, understand the impact of sFlt-1 on the pathogenesis of preeclampsia.2. Analysis of peripheral blood concentration of sFlt and correlation of adverse pregnancy outcomes. Method:60 cases of severe preeclampsia patients,30 cases of mild preeclampsia,30 healthy pregnant women. Compared three groups of pregnant women in General and sFlt-1 in peripheral blood concentration differences, gestational and neonatal weight. Result:SFlt-1 there are significant differences between the three group (P＜0.01). Severe neonatal weight less than mild and control groups, mild group and control group no significant difference (P>0.05)。Conclusion:Peripheral blood of preeclampsia sFlt-1 level is significantly higher than in normal pregnant women, sFlt-1 levels and the extent of the disease concerned.
Part 3:Early onset and late onset severe pre-eclampsia's basic, clinical indicators, pregnancy outcomes and relationship sFlt-1
Objective:Analysis of early-onset severe preeclampsia and late onset severe preeclampsia of differences, as well as the relationship between sFlt-1 and clinical parameters to explore early-onset time of interruption of pregnancy.Method:Study on 60 cases of patients with severe preeclampsia, and is divided into early onset and late onset (bounded by 34 weeks), two sets of complications, clinical laboratory indicators, statistical analysis of the differences in perinatal outcomes. Result: Early-onset severe preeclampsia complicated a high proportion of gestational diabetes mellitus and chronic high blood pressure. A high proportion of newborns small for gestational age infants. Laboratory examination of liver enzyme is higher than late-onset group. No significant difference in the concentration of sFlt-1. sFlt-1 is positive correlation with 24h protein in urine, umbilical blood flow S/D and MAP. In the early-onset have positive correlation between sFlt-1 and serum uric acid in, and neonatal weight inversely correlated, and no obvious correlation in late-onset. Conclusion:Early-onset severe pre-eclampsia patients and patients with late-onset pathogenesis differences might exist.sFlt-1 is a key factors in neonatal weight, blood pressure, protein in urine. Close monitoring of sFlt-1 levels help to choose the best timing of interruption pregnancy.
Part 4:The relationship between the level of sFlt-1 during pregnancy and postpartum recovery
10 cases of severe preeclampsia return visit, the outcome of cases, patients with severe postpartum preeclampsia track.The recovery of patients with post-partum preeclampsia are different._Proteinuria and prenatal postpartum continued high levels of sFlt-1 related. Persistent proteinuria and hypertension after delivery is related with high level of sFlt-1 during pregnancy。High levels of sFlt-1 during pregnancy may cause future cardiovascular disease.
引文
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[31]Maynard S E, Thadhani R. Pregnancy and the kidney.[J]. J Am Soc Nephrol,2009,20(1):14-22.
[32]Levine R J, Qian C, Maynard S E, et al. Serum sFltl concentration during preeclampsia and mid trimester blood pressure in healthy nulliparous women.[J]. Am J Obstet Gynecol,2006,194(4):1034-1041.
[33]刘学敏,陈震宇,王桂喜,et al孕前体重指数及其孕期增加对妊娠结局的 影响[J].中国妇幼保健,2010,25(22)：3084-3087.
[34]周丽霞,王巧玲.孕期体重指数及其增长水平在妊娠糖尿病筛查中的应用[J].中国医药导报,2009：25-26.
[35]Kosa J L, Guendelman S, Pearl M, et al. The Association Between Pre-pregnancy BMI and Preterm Delivery in a Diverse Southern California Population of Working Women.[J]. Matern Child Health J,2010.
[36]Mantakas A, Farrell T. The influence of increasing BMI in nulliparous women on pregnancy outcome.[J]. Eur J Obstet Gynecol Reprod Biol,2010,153(1):43-46.
[37]Lombardi D G, Barton J R, O'Brien J M, et al. Does an obese prepregnancy body mass index influence outcome in pregnancies complicated by mild gestational hypertension remote from term?[J]. Am J Obstet Gynecol,2005,192(5):1472-1474.
[38]Suwaki N, Masuyama H, Nakatsukasa H, et al. Hypoadiponectinemia and circulating angiogenic factors in overweight patients complicated with pre-eclampsia.[J]. Am J Obstet Gynecol,2006,195(6):1687-1692.
[39]Maynard S E, Thadhani R. Pregnancy and the kidney.[J]. J Am Soc Nephrol,2009,20(1):14-22.
[40]杨孜,林其德.子痫前期-子痫的病理生理学研究[J].中华妇产科杂志,2006,41(8)：507-508.
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[47]黄雪文,黄金智.105例子痫前期的临床特点与围产结局的临床观察[J].广东医学院学报,2010,28(3)：268-269.
[48]李海英.早发型重度子痫前期76例临床观察[J].中国妇幼保健,2010,25(20)：2810-2811.
[49]Haddad B, Sibai B M. Expectant management of severe preeclampsia:proper candidates and pregnancy outcome.[J]. Clin Obstet Gynecol,2005,48(2):430-440.
[50]Valensise H, Vasapollo B, Gagliardi G, et al. Early and late preeclampsia:two different maternal hemodynamic states in the latent phase of the disease. [J]. Hypertension,2008,52(5):873-880.
[51]何玉洁,成要平.重度子痫前期患者超声心动图检查的临床意义[J].中华妇幼临床医学杂志(电子版),2010,6(5)：355-356.
[52]郝丽英,王琪,李阳.子痫前期患者血流动力学类型及在妊娠不良结局预测中的应用[J].中华临床医师杂志(电子版),2010,4(8)：150-152.
[53]Gyselaers W, Mesens T, Tomsin K, et al. Maternal renal interlobar vein impedance index is higher in early-than in late-onset pre-eclampsia.[J]. Ultrasound Obstet Gynecol,2010,36(1):69-75.
[54]马小卿,吴青青,李萍,etal三维能量彩色多普勒超声用于检测子痫前期孕妇胎盘组织血流灌注的价值[J].中华妇产科杂志,2009,44(3)：179-182.
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[58]林建华,乐怡平.早发型子痫前期期待治疗[J].实用妇产科杂 志,2010：804-807.
[59]Sarsam D S, Shamden M, Al W R. Expectant versus aggressive management in severe preeclampsia remote from term.[J]. Singapore Med J,2008,49(9):698-703.
[60]Berks D, Steegers E A, Molas M, et al. Resolution of hypertension and proteinuria after preeclampsia.[J]. Obstet Gynecol,2009,114(6):1307-1314.
[61]Martillotti G, Boulvain M, Landau R, et al. [Is preeclampsia a new cardiovascular and end-stage renal diseases risk marker?].[J]. Rev Med Suisse,2009,5(216):1752-1754,1756-1757.
[62]Liu X, Zhou Z, Cao Y, et al. Contributions of blood pressure to proteinuria and renal function in the puerperium.[J]. Blood Press,2009,18(6):362-366.
[63]陈蕾,杨孜.早发型重度子痫前期的母儿预后[J].实用妇产科杂志,2010：810-812.
[64]Byers B D, Betancourt A, Lu F, et al. The effect of prepregnancy obesity and sFlt-1-induced preeclampsia-like syndrome on fetal programming of adult vascular function in a mouse model.[J]. Am J Obstet Gynecol,2009,200(4):431-432.
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[26]Buchbinder A, Sibai B M, Caritis S, et al. Adverse perinatal outcomes are significantly higher in severe gestational hypertension than in mild preeclampsia.[J]. Am J Obstet Gynecol,2002,186(1):66-71.
[27]杨孜,王伽略,黄萍,et al重度子痫前期终末器官受累不平行性及其围产结局探讨[J].中华围产医学杂志,2006,9(1)：10-14.
[28]杨雪芳,陈皆锋,阮秀兰,et al早发型重度子痫前期发病及母婴结局的临床分析[J].实用妇产科杂志,2010：146-148.
[29]林建华,乐怡平.早发型子痫前期期待治疗[J].实用妇产科杂志,2010：804-807.
[30]Bergmann A, Ahmad S, Cudmore M, et al. Reduction of circulating soluble Flt-1 alleviates preeclampsia-like symptoms in a mouse model.[J]. J Cell Mol Med,2010,14(6B):1857-1867.
[31]Maynard S E, Thadhani R. Pregnancy and the kidney.[J]. J Am Soc Nephrol,2009,20(1):14-22.
[32]Levine R J, Qian C, Maynard S E, et al. Serum sFltl concentration during preeclampsia and mid trimester blood pressure in healthy nulliparous women.[J]. Am J Obstet Gynecol,2006,194(4):1034-1041.
[33]刘学敏,陈震宇,王桂喜,et al孕前体重指数及其孕期增加对妊娠结局的 影响[J].中国妇幼保健,2010,25(22)：3084-3087.
[34]周丽霞,王巧玲.孕期体重指数及其增长水平在妊娠糖尿病筛查中的应用[J].中国医药导报,2009：25-26.
[35]Kosa J L, Guendelman S, Pearl M, et al. The Association Between Pre-pregnancy BMI and Preterm Delivery in a Diverse Southern California Population of Working Women.[J]. Matern Child Health J,2010.
[36]Mantakas A, Farrell T. The influence of increasing BMI in nulliparous women on pregnancy outcome.[J]. Eur J Obstet Gynecol Reprod Biol,2010,153(1):43-46.
[37]Lombardi D G, Barton J R, O'Brien J M, et al. Does an obese prepregnancy body mass index influence outcome in pregnancies complicated by mild gestational hypertension remote from term?[J]. Am J Obstet Gynecol,2005,192(5):1472-1474.
[38]Suwaki N, Masuyama H, Nakatsukasa H, et al. Hypoadiponectinemia and circulating angiogenic factors in overweight patients complicated with pre-eclampsia.[J]. Am J Obstet Gynecol,2006,195(6):1687-1692.
[39]Maynard S E, Thadhani R. Pregnancy and the kidney.[J]. J Am Soc Nephrol,2009,20(1):14-22.
[40]杨孜,林其德.子痫前期-子痫的病理生理学研究[J].中华妇产科杂志,2006,41(8)：507-508.
[41]Kulikov A V, Spirin S V, Blauman S I. [Clinicopathologic characteristics of HELLP-syndrome].[J]. Anesteziol Reanimatol,2010(6):87-91.
[42]Madsen B S, Havelund T. [HELLP in the second trimester in a patient with antiphospholipid syndrome].[J]. Ugeskr Laeger,2011,173(5):357-358.
[43]Vinnars M T, Wijnaendts L C, Westgren M, et al. Severe preeclampsia with and without HELLP differ with regard to placental pathology.[J]. Hypertension,2008,51(5):1295-1299.
[44]Varkonyi T, Nagy B, Fule T, et al. Microarray profiling reveals that placental transcriptomes of early-onset HELLP syndrome and preeclampsia are similar.[J]. Placenta,2011,32 Suppl:S21-S29.
[45]Yoshimatsu J, Matsumoto H, Goto K, et al. Relationship between urinary albumin and serum soluble fms-like tyrosine kinase 1 (sFlt-1) in normal pregnancy.[J]. Eur J Obstet Gynecol Reprod Biol,2006,128(1-2):204-208.
[46]Martin A C, Brown M A. Could uric acid have a pathogenic role in pre-eclampsia?[J]. Nat Rev Nephrol,2010,6(12):744-748.
[47]黄雪文,黄金智.105例子痫前期的临床特点与围产结局的临床观察[J].广东医学院学报,2010,28(3)：268-269.
[48]李海英.早发型重度子痫前期76例临床观察[J].中国妇幼保健,2010,25(20)：2810-2811.
[49]Haddad B, Sibai B M. Expectant management of severe preeclampsia:proper candidates and pregnancy outcome.[J]. Clin Obstet Gynecol,2005,48(2):430-440.
[50]Valensise H, Vasapollo B, Gagliardi G, et al. Early and late preeclampsia:two different maternal hemodynamic states in the latent phase of the disease. [J]. Hypertension,2008,52(5):873-880.
[51]何玉洁,成要平.重度子痫前期患者超声心动图检查的临床意义[J].中华妇幼临床医学杂志(电子版),2010,6(5)：355-356.
[52]郝丽英,王琪,李阳.子痫前期患者血流动力学类型及在妊娠不良结局预测中的应用[J].中华临床医师杂志(电子版),2010,4(8)：150-152.
[53]Gyselaers W, Mesens T, Tomsin K, et al. Maternal renal interlobar vein impedance index is higher in early-than in late-onset pre-eclampsia.[J]. Ultrasound Obstet Gynecol,2010,36(1):69-75.
[54]马小卿,吴青青,李萍,etal三维能量彩色多普勒超声用于检测子痫前期孕妇胎盘组织血流灌注的价值[J].中华妇产科杂志,2009,44(3)：179-182.
[55]Wikstrom A K, Larsson A, Eriksson U J, et al. Placental growth factor and soluble FMS-like tyrosine kinase-1 in early-onset and late-onset preeclampsia.[J]. Obstet Gynecol,2007,109(6):1368-1374.
[56]Sibai B M, Koch M A, Freire S, et al. The impact of prior preeclampsia on the risk of superimposed preeclampsia and other adverse pregnancy outcomes in patients with chronic hypertension.[J]. Am J Obstet Gynecol,2011,204(4):341-345.
[57]Jeevaratnam K, Nadarajah V D, Judson J P, et al. Periodic assessment of plasma sFlt-1 and PlGF concentrations and its association with placental morphometry in gestational hypertension (GH)-a prospective follow-up study.[J]. BMC Pregnancy Childbirth,2010,10:58.
[58]林建华,乐怡平.早发型子痫前期期待治疗[J].实用妇产科杂 志,2010：804-807.
[59]Sarsam D S, Shamden M, Al W R. Expectant versus aggressive management in severe preeclampsia remote from term.[J]. Singapore Med J,2008,49(9):698-703.
[60]Berks D, Steegers E A, Molas M, et al. Resolution of hypertension and proteinuria after preeclampsia.[J]. Obstet Gynecol,2009,114(6):1307-1314.
[61]Martillotti G, Boulvain M, Landau R, et al. [Is preeclampsia a new cardiovascular and end-stage renal diseases risk marker?].[J]. Rev Med Suisse,2009,5(216):1752-1754,1756-1757.
[62]Liu X, Zhou Z, Cao Y, et al. Contributions of blood pressure to proteinuria and renal function in the puerperium.[J]. Blood Press,2009,18(6):362-366.
[63]陈蕾,杨孜.早发型重度子痫前期的母儿预后[J].实用妇产科杂志,2010：810-812.
[64]Byers B D, Betancourt A, Lu F, et al. The effect of prepregnancy obesity and sFlt-1-induced preeclampsia-like syndrome on fetal programming of adult vascular function in a mouse model.[J]. Am J Obstet Gynecol,2009,200(4):431-432.
[1]Roberts J M. Preeclampsia:what we know and what we do not know.[J]. Semin Perinatol,2000,24(1):24-28.
[2]Lim K H, Zhou Y, Janatpour M, et al. Human cytotrophoblast differentiation/invasion is abnormal in pre-eclampsia.[J]. Am J Pathol,1997,151(6):1809-1818.
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