子痫前期患者胎盘组织氧化应激与PeroxiredoxinⅡ

目的:研究子痫前期胎盘组织氧化应激情况及PeroxiredoxinⅡ的表达,探讨PeroxiredoxinⅡ在子痫前期氧化应激机制中的作用。方法:用蛋白免疫印迹法检测15例子痫前期患者及15例正常妊娠者胎盘组织中PeroxiredoxinⅡ表达,测定相应组织中SOD活力及MDA、H2O2含量。结果:子痫前期患者胎盘组织中,PeroxiredoxinⅡ的表达明显低于正常妊娠组(P<0.05)。子痫前期组氧化应激指标SOD活力为89.74±18.26U/mg-prot,明显低于正常妊娠组105.23±21.88U/mgprot(P<0.01);MDA含量96.69±32.88nmol/mgprot,明显高于对照组63.29±13.74nmol/mgprot(P<0.05);H2O2含量为81.65±17.93nmol/mgprot,显著高于对照组的68.58±13.55nmol/mgprot(P<0.01)。H2O2含量与PeroxiredoxinⅡ表达量呈负相关。结论:PeroxiredoxinⅡ与子痫前期发生发展中的氧化应激机制存在密切关系。     

胎盘及外周血中STBM与早发型重度子痫前期病因的研究

目的:测定孕妇胎盘组织和血清合体滋养细胞层微绒毛膜(STBM)在重度子痫前期的表达情况,揭示早发型与晚发型重度子痫前期可能具有不同的病因及发病机制.方法:收集在我院治疗的早发型与晚发型重度予痫前期患者各15例,及与两组孕周相匹配正常妊娠孕妇各10例.采用实时荧光定量PCR(Real-time RT-PCR)方法测重度子痫前期患者胎盘中STBM的标记物TPAmRNA水平,另用酶联免疫分析法(ELLSA)测定血清和胎盘中STBM的标记物TPA蛋白表达水平.结果:①早发型组孕妇胎盘STBM的标记物TPA相对含量(2.04±0.32 ng/ml),高于晚发型组(1.75±0.31 ng/ml)(P＜0.05),早发型组胎盘STBM的标记物TPA mRNA含量(0.0342±0.0021)高于晚发组(0.0222±0.0020)(P＜0.05);②早发型组孕妇血清中STBM的标记物TPA水平(1.88±0.43 n#m1)高于晚发型组(1.59±0.26 ng/ml)(p＜0.05).早发型组和晚发型组血清中STBM的标记物TPA水平均高于同期正常孕妇血清中的TPA水平(P均＜0.05).③早发型组孕妇胎盘组织中STBM的标记物TPA水平与血清尿素氮水平、血清肌酐水平、S/D比值之间均呈显著正相关.晚发型组中与血清肌酐水平之间呈显著正相关.④早发型组孕妇血清中STBM的标记物TPA水平与血清肌酐水平、收缩压、舒张压之间均呈显著正相关.晚发型组中与血清肌酐水平、S/D比值、收缩压之间均呈显著正相关.结论:早发型重度子痫前期胎盘的合体滋养细胞凋亡早且严重,早发型与晚发型重度子痫前期可能具有不同的病因及发病机制.     

晚发型重度子痫前期患者胎盘中微小RNA-152及血清中可溶性人类白细胞抗原G蛋白的表达及其关系

目的 探讨胎盘中微小RNA(micro-ribonucleic acid,miRNA)-152及血清中可溶性人类白细胞抗原G(soluble human leukocyte antigen-G,sHLA-G)蛋白在重度子痫前期发病中的作用.方法 选择2010年7月至2012年3月在镇江市妇幼保健院妇产科产前检查并剖宫产分娩的20例妊娠36～40周的晚发型重度子痫前期患者,选择孕周匹配的20例剖宫产产妇作为正常对照组.采用实时荧光定量聚合酶链反应技术检测胎盘组织miRNA-152的表达:采用酶联免疫吸附试验检测血清sHLA-G蛋白含量.2组miRNA-152与sHLA-G差异比较采用两独立样本t检验,相关性采用Pearson相关分析. 结果 miRNA-152在重度子痫前期组胎盘中的表达为512.6±52.3,明显高于对照组(175.6±18.4),差异有统计学意义(t=7.06,P＜0.01).重度子痫前期组血清中sHLA-G的含量为(19.7±5.2) U/ml,明显低于正常对照组[(34.3±10.2) U/ml],差异有统计学意义(t=5.01,P＜0.05).重度子痫前期组和对照组胎盘组织miRNA-152与血清中sHLA-G表达均呈负相关(r=-0.52和-0.57,P＜0.05). 结论 miR-152在晚发型重度子痫前期患者胎盘组织中表达升高,使HLA-G mRNA的稳定性降低,产生基因沉默影响转录,导致血清sHLA-G表达减少,可能与晚发型重度子痫前期的发病有一定相关性.     

孕妇血清及其新生儿脐血、胎盘组织中脂肪型脂肪酸结合蛋白表达变化与子痫前期发病的关系

目的 探讨孕妇血清及其新生儿脐血中脂肪型脂肪酸结合蛋白(FABP4)水平、胎盘组织中FABP4 mRNA的表达变化在子痫前期发病中的作用.方法 选择2008年12月-2009年10月在福建省妇幼保健院产科住院分娩的60例重度子痫前期孕妇,按发病时孕周不同分为早发型子痫前期组(发病时孕周≤34周)和晚发型子痫前期组(发病时孕周>34周)各30例;另选同期正常晚期孕妇60例,根据孕周不同分为早发型对照组(孕周≤34周)和晚发型对照组(孕周>34周)各30例.采用酶联免疫吸附试验(ELISA)检测孕妇血清FABP4、空腹血糖(FPG)、空腹胰岛素(FINS)及新生儿脐血FABP4水平;采用稳态模型评估法计算胰岛素抵抗指数(HOMA-IR);采用逆转录(RT)PCR技术检测胎盘组织中FABP4 mRNA的表达;记录临床相关指标,包括孕妇入院时体质指数(BMI)、收缩压(SP)、舒张压(DP)及平均动脉压(MAP)、血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)、肌酐(Cr)、尿酸(UA)、肾小球滤过率(GFR)、24 h尿蛋白定量和新生儿出生体质量.结果 (1)早发型及晚发型子痫前期组孕妇血清中FABP4水平分别为(176±9)及(170±9)ng/L,早发型及晚发型对照组分别为(81±13)及(94±15)ng/L,分别比较,差异均有统计学意义(P<0.05).(2)早发型及晚发型子痫前期组孕妇血清FINS、HOMA-IR水平分别为(21.9±4.3)mU/L、5.1±1.7及(22.6±4.0)mU/L、4.9±1.5,分别比较,差异均有统计学意义(P<0.05).(3)早发型及晚发型子痫前期组孕妇胎盘组织中FABP4 mRNA的表达水平分别为3.17±0.89及2.97±0.72,均高于晚发型对照组的1.00±0.28,分别比较,差异均有统计学意义(P<0.05);但早发型子痫前期组与晚发型子痫前期组比较,差异无统计学意义(P>0.05).(4)早发型及晚发型子痫前期组新生儿脐血中FABP4水平分别为(92±10)及(100±8)ng/L,均低于晚发型对照组的(141±18)ng/L,分别比较,差异均有统计学意义(P<0.05).早发型子痫前期组、晚发型子痫前期组及晚发型对照组新生儿出生体质量两两比较,差异均有统计学意义(P<0.05).相关性分析结果显示,脐血FABP4水平与孕妇血清FABP4及胎盘组织中FABP4 mRNA表达水平均呈明显负相关(r分别为-0.882、-0.678,P<0.05),与新生儿出生体质量呈明显正相关(r=0.728,P<0.05).(5)早发型及晚发型子痫前期组孕妇血清中FABP4水平与胎盘组织中FABP4 mRNA表达水平均呈明显正相关(r分别为0.609、0.403,P<0.05),与血TG(r分别为0.702、0.562),FINS(r分别为0.528、0.423),HOMA-IR(r分别为0.566、0.519),Cr(r分别为0.443、0.523),UA(r分别为0.438、0.413)均呈明显正相关(P<0.05),而与血HDL(r分别为-0.539、-0.498),GFR(r分别为-0.717、-0.778)均呈明显负相关(P<0.05).结论 子痫前期孕妇血清FABP4水平及胎盘组织中FABP4 mRNA表达水平均明显升高,且两者呈明显正相关.提示FABP4水平升高可能是子痫的期发病的重要因素之一,而胎盘组织中FABP4 mRNA表达水平升高可能是导致子痫的期孕妇血清FABP4水平升高的主要原因.     

子痫前期患者血清及胎盘组织中人类白细胞抗原G的表达研究

目的:检测正常晚期妊娠妇女及子痫前期患者胎盘组织HLA-G的表达及血清中sHLA-G的浓度,探讨HLA-G在子痫前期发病中的临床意义。方法:用半定量逆转录-聚合酶链技术(RT-PCR)检测37例正常晚期妊娠妇女(正常妊娠组)及41例子痫前期患者(轻度20例,重度21例)胎盘组织中HLA-G mRNA的表达;并用ELISA检测血清sHLA-G浓度。结果:(1)子痫前期胎盘组织中HLA-G mRNA表达水平分别为:轻度0.402±0.104、重度0.329±0.09,明显低于正常妊娠组的0.628±0.117(P<0.01),轻、重度差异亦有统计学意义(P<0.05)。(2)子痫前期血清sHLA-G浓度:轻度45.5±11.9u/ml,重度31.2±10.3u/ml,均明显低于正常妊娠组的105.7±12.5u/ml(P<0.01),轻重度差异亦有统计学意义(P<0.01)。(3)子痫前期患者血清sHLA-G浓度与胎盘组织HLA-G mRNA表达水平呈正相关(r=0.702,P<0.01)。结论:子痫前期血清sHLA-G浓度及胎盘组织中HLA-G表达水平均明显降低,可能与子痫前期发病及病情轻重程度相关。     

重度子痫前期患者胎盘合体滋养细胞凋亡的研究

目的 比较早发型与晚发型重度子痫前期患者胎盘合体滋养细胞凋亡水平变化,探讨其病因及发病机制的差异.方法 选择2008年11月至2009年5月在上海交通大学附属第六人民医院住院剖宫产分娩的早发型重度子痫前期患者15例(早发型组)、晚发型重度子痫前期患者15例(晚发型组)和健康妊娠妇女10例(对照组),采用酶联免疫吸附试验检测孕妇血浆中合体滋养细胞微粒(STBM)水平,蛋白印迹法检测胎盘组织中凋亡蛋白--半胱氨酸天冬氨酸蛋白酶3(caspase-3)蛋白表达水平.结果 (1)STBM:早发型组孕妇血浆STBM水平为(71±21)μg/L,高于晚发型组的(42±30)μg/L和对照组的(26±11)μg/L,分别比较,差异均有统计学意义(P＜0.05);晚发型组血浆STBM水平与对照组比较,差异无统计学意义(P＞0.05).(2)caspase-3蛋白:早发型组胎盘组织中caspase-3蛋白表达水平为0.85±0.61,晚发型组为0.77±0.46,对照组为0.32±0.15,早发型和晚发型组胎盘组织中caspase-3蛋白表达水平均高于对照组,差异有统计学意义(P＜0.05);但早发型组和晚发型组比较,差异无统计学意义(P＞0.05).结论 早发型与晚发型重度子痫前期可能存在不同的发病机制,早发型重度子痫前期可能是一种胎盘疾病,而晚发型则可能与母体因素有关.     

早发型重度子痫前期与血浆同型半胱氨酸浓度相关性及相应治疗

目的 探讨早发型重度子痫前期与血浆总同型半胱氨酸(tHcy)浓度的相关性和血清叶酸、维生素B12:(VitB12)水平及其治疗.方法 选取2006年1月至2008年2月沈阳军区第202医院收治的旱发型重度子痫前期患者70例(早发组)、晚发型重度子痫前期患者70例(晚发组)、正常妊娠妇女70例(对照组),测定其血浆tH-cy、血清叶酸及VitB12.并对早发型重度子痫前期伴高同型半胱氨酸血症患者分为两组:单用叶酸组(A组)及叶酸联合甲钴胺组(B组),两组均给予叶酸5mg,每日3次,B组再加用甲钴胺500ug,每日1次,疗程2周,测定治疗前后患者血浆tHcy和血清叶酸、VitB12.结果 早发组及晚发组血浆tHcy[分别为(16.34±4.13)umol/L及(11.28±3.54)umol/L]与对照组[(5.77±2.12)umol/L]相比,P<0.01;且早发组与晚发组相比P<0.01.早发组中30例伴高Hcy血症患者经治疗2周后,A组血浆tHcy[(9.18±2.56)umol/L]与治疗前[(16.21±4.04)umol/L]比较,B组血浆tHcy浓度[(8.96±2.78)umol/L]与治疗前[(15.89±3.23)umol/L]比较均有显著下降(P<0.01).结论 早发型重度子痫前期的病因可能与患者血浆tHcy显著上升有关;叶酸可能成为早发型重度子痫前期期待治疗的辅助用药.     

高迁移率族蛋白1及其受体晚期糖基化终末产物的表达与子痫前期发病的关系

目的 探讨高迁移率族蛋白1(HMGB1)及其受体晚期糖基化终末产物(RAGE)表达与子病前期发病的关系.方法 2006年3月至2007年3月中国医科大学附属盛京医院住院分娩的15例早发型子痫前期孕妇(早发型子痫前期组)、22例重度子痫前期孕妇(晚发型子痫前期组)、12例正常足月孕妇(正常对照组).采用链霉亲和素-生物素-过氧化物酶复合物法检测3组孕妇胎盘组织中HMGB1和RAGE的蛋白定位及表达情况.结果 (1)HMGB1蛋白定位及分布:正常对照组孕妇胎盘组织中无或仅有极少量HMGB1弱阳性细胞,主要见于滋养细胞层、单核巨噬细胞、蜕膜细胞、血管平滑肌细胞、血管内皮细胞和绒毛间质细胞,HMGB1在胞质内呈弥漫性分布,并呈略高于背景的淡棕黄色;晚发型子痫前期组孕妇胎盘组织中HMGB1阳性细胞分布与正常对照组一致,但HMGB1阳性细胞数量明显增多,染色强度也明显增强;早发型子痫前期孕妇胎盘组织中HMGB1主要分布于细胞滋养细胞,细胞核内可见深棕色染色,核膜皱缩.(2)RAGE蛋白定位及分布:正常对照组孕妇胎盘组织中无或仅有极少量RAGE弱阳性细胞,RAGE主要见于合体滋养细胞、血管内皮细胞,细胞膜和(或)细胞质内呈略高于背景的淡棕黄色染色;晚发型子痫前期组孕妇RAGE阳性细胞分布与正常对照组一致,但RAGE阳性细胞数量明显增多,染色强度也明显增强;早发型子痫前期组孕妇RAGE主要见于滋养细胞层,细胞呈RAGE强阳性表达.(3)HMGB1蛋白阳性表达率:早发型子痫前期组为73%(11/15),晚发型子痫前期组为64%(14/22),两组比较,差异无统计学意义(P>0.05);但两组均明显高于正常对照组的17%(2/12),差异有统计学意义(P<0.05).(4)RAGE蛋白阳性表达率:早发型子痫前期组为80%(12/15),晚发型子痫前期组为82%(18/22),两组比较,差异无统计学意义(P>0.05);但两组均明显高于正常对照组的25%(3/12),差异有统计学意义(P<0.05).结论 子痫前期孕妇胎盘组织中的HMGB1和RAGE蛋白表达水平升高,可能是子痫前期发病的重要机制之一;HMGB1和RAGE在早发型和晚发型子痫前期孕妇胎盘组织中的表达部位不同,可能与不同临床类型的子痫前期发生有关.     

血清胱抑素C水平与早发型子痫前期发生和不良妊娠结局关系探讨

目的:研究孕妇发生早发型子痫前期及其出现不良妊娠结局与血清胱抑素C(CC)水平变化趋势关系。方法:选取2009年7月至2011年7月在南方医科大学南方医院妇产科住院治疗并分娩的早发型子痫前期患者69例,其中轻度15例(早发轻度组),重度54例(早发重度组),分析血清CC水平和子痫前期发生及母儿结局的关系。并同期选择产前检查正常的妊娠孕妇100例,检测其孕中期和孕晚期血清CC水平作为对照。结果:①正常妊娠孕妇孕中期和孕晚期时血清CC分别为0.81±0.12mmol/L和1.01±0.18mmol/L。早发轻度组血清CC(1.15±0.39mmol/L)和早发重度组血清CC(1.69±0.68mmol/L),分别与正常妊娠孕妇的孕中期和孕晚期比较,差异均有统计学意义(P<0.05)。②早发重度组的血清CC水平高于早发轻度组(P<0.05);早发重度组收缩压、舒张压、尿酸、肌酐和24小时尿蛋白水平均明显高于早发轻度组(P<0.05);早发重度组的羊水过少、胎儿生长受限、胎死宫内、低蛋白血症、胎盘早剥和HEELP综合征等不良妊娠的发生率高于早发轻度组。③早发重度组中出现不良妊娠结局患者中的CC水平高于未出现不良妊娠结局患者(P<0.05)。结论:子痫前期患者在妊娠中期血清CC水平已高于正常妊娠妇女,可能与子痫前期的发生和不良妊娠结局的出现相关。     

HIF-1α、VEGF及MVD在子痫前期不同发病类型胎盘的表达

目的:探讨缺氧诱导因子1α(HIF-1α)、靶基因血管内皮生长因子(VEGF)及微血管密度(MVD)在子痫前期患者胎盘组织的表达及与胎盘血管病变的关系。方法:用链酶菌抗生物素蛋白-过氧化物酶连接(SP)法检测早发型,晚发型重度子痫前期患者和正常妊娠妇女(对照组)胎盘组织中HIF-1α、VEGF的表达,并计数胎盘微血管密度(MVD)值,并进行相关性分析。结果:(1)子痫前期患者胎盘组织中HIF-1α阳性表达率明显高于正常对照组,差异有统计学意义(P<0.05),早发型、晚发型子痫前期组HIF-1α与正常对照组的差异有统计学意义(P<0.05),早发型组HIF-1α阳性表达率高于晚发型组,两者差异有统计学意义(P<0.05);(2)子痫前期患者胎盘组织中VEGF阳性表达率低于正常对照组,两者差异有统计学意义(P<0.05),而早发型组VEGF阳性表达率低于晚发型组,差异亦有统计学意义(P<0.05);(3)正常对照组,晚发型子痫前期组,早发型子痫前期组MVD计数依次递减,子痫前期组与正常对照组比较有统计学差异(P<0.05),早发型组与晚发型组比较有统计学差异(P<0.05);(4)子痫前期组和正常对照组胎盘中HIF-1α表达与VEGF及MVD值的变化呈显著负相关(r=-0.562,P<0.05;r=-0.622,P<0.05),VEGF及MVD值的变化则呈显著正相关(r=0.718,P<0.05)。结论:HIF-1α在子痫前期患者胎盘组织中表达升高,通过下调靶基因VEGF,引起VEGF降低,影响胎盘血管重铸,参与子痫前期的发生和发展。     

慢性高血压并发早发型重度先兆子痫单胎孕妇围产期母儿结局的回顾性分析

目的探讨慢性高血压并发早发型重度先兆子痫较单纯早发型重度先兆子痫是否会增加母儿的不良结局。方法自1999年7月1日至2009年6月30日北京大学第一医院共收治早发型重度先兆子痫单胎孕妇300例,其中慢性高血压并发早发型重度先兆子痫者59例(A组),单纯早发型重度先兆子痫者241例(B组),对两组孕妇的母儿结局进行分析,讨论慢性高血压并发早发型重度先兆子痫是否会增加母儿的不良结局。结果两组孕妇一般情况没有明显的差异,A组的最高收缩压和舒张压明显高于B组(P0.05)。两组孕妇严重并发症如胎盘早剥、HELLP综合征、肺水肿、肝功能损害和子痫等发生率比较,差异无统计学意义(P0.05)。A组除了新生儿呼吸窘迫综合征的发生率明显高于B组外(P0.05),两组围产儿死亡率、胎儿生长受限、新生儿窒息、颅内出血和坏死性小肠结肠炎的发生率比较,差异无统计学意义(P0.05)。结论在病情允许的情况下,通过严密监测母儿一般状况、积极地对症治疗并采用适当的期待疗法,慢性高血压并发早发型重度先兆子痫较单纯早发型重度先兆子痫没有对母儿造成明显的不良后果。     

Maternal plasma concentrations of the placental specific sFLT-1 variant,sFLT-1 e15a,in fetal growth restriction and preeclampsia

Objective: sFLT-1 e15a is a recently described sFlt-1 variant that is placental and primate specific. As such, it may have potential as a biomarker. Using a newly developed ELISA, we measured maternal plasma sFLT-1 e15a levels in women with fetal growth restriction and pre-eclampsia.

Method: We performed a nested case-control study where we measured total sFLT-1 and sFLT-1 e15a plasma protein concentrations. Samples, selected from a prospective cohort study, consisted of 87 healthy controls, 11 cases that developed term preeclampsia and 20 cases where there was fetal growth restriction. We also measured sFLT-1 and sFLT-1 e15a plasma concentrations in a separate cohort: 15 cases of preterm preeclampsia and 24 healthy controls.

Results: The prospective case-control cohort demonstrated significantly increased sFLT-1 e15a among cases with term fetal growth restriction (p?p?p?Conclusion: Plasma sFLT-1 e15a is significantly increased in early-onset preeclampsia and term fetal growth restriction. Further assessment of the benefit for sFLT-1 e15a testing in prediction or diagnosis of these disease states is warranted.     

Second-trimester levels of maternal serum human chorionic gonadotropin and inhibin a as predictors of preeclampsia in the third trimester of pregnancy

OBJECTIVE: To determine whether second-trimester maternal serum levels of inhibin A, human chorionic gonadotropin (hCG), unconjugated estriol (uE3), and alpha-fetoprotein (AFP) are predictive of the later onset of preeclampsia in pregnancy. METHODS: Retrospective evaluation of serum analyte levels in 60 women with preeclampsia compared with 300 controls. Levels of each analyte were compared in women with preeclampsia and controls using matched rank analysis. Analytes that were significantly different between groups were examined with univariate and bivariate Gaussian distribution analysis. RESULTS: Second-trimester inhibin A (1.36 multiples of the median [MoM]) and hCG (1.40 MoM) levels were significantly but modestly elevated in women who later developed preeclampsia. A combination test of maternal age plus inhibin A and hCG predicted 23% of cases of preeclampsia with 95% specificity. There was a statistically significant trend for inhibin A, but not hCG, levels to be higher when the onset of preeclampsia occurred within a shorter (<17 weeks) interval after collection of the second-trimester screening sample. CONCLUSIONS: Second-trimester serum levels of inhibin A and hCG are modest predictors of the later onset of preeclampsia. Inhibin A may be a better predictor of early-onset preeclampsia, which is associated with a higher maternal and perinatal morbidity and mortality, than preeclampsia at or near term.     

不同亚型子痫前期患者母儿结局分析

目的分析不同亚型子痫前期患者的母儿结局。 方法回顾性分析2009年1月1日至2019年12月31日在广州医科大学附属第三医院分娩的2960例单胎子痫前期患者早产组与足月产组、早发型组与晚发型组的临床资料及母儿结局。 结果(1)母亲结局：①早产组与足月产组剖宫产率分别为(80.85% vs 61.67%, χ²＝1.327)、入住重症监护病房率(11.84% vs 2.25%, χ²＝86.844)，P值均<0.05；②早发型与晚发型剖宫产率分别为(77.61% vs 70.30%, χ²＝1.327，P<0.05)、入住重症监护病房率(13.00% vs 4.55%, χ²＝69.158，P<0.05)。(2)新生儿结局：①早产组与足月产组在新生儿出生平均体重[(1472.19±673.50)g与(3067.49±523.92)g，Z＝-42.4]，活产比例(81.35% vs 99.31%, χ²＝2.204)，新生儿窒息率(6.39% vs 0.79%, χ²＝53.51)P均<0.05。②早发型组与晚发型组新生儿出生体重[(1169.53±482.39)g vs(2765.37±683.22)g，Z＝-43.895]，活产比例(74.64% vs 98.31%, χ²＝3.926)，新生儿窒息率(8.71% vs 1.31%, χ²＝86.82)，差异均有统计学意义(P<0.05)。 结论子痫前期患者早产组与足月产组相比，早产组母体及新生儿结局均较差。早发型与晚发型子痫前期相比，早发型母儿结局均较差。     

Second-trimester maternal serum placental growth factor and vascular endothelial growth factor for predicting severe,early-onset preeclampsia

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.     

Relationship between ABO blood groups and preeclampsia

ABSTRACT

Objective

To investigate the relationship between ABO blood group and preeclampsia.Methods: A case-control study was conducted, including 230 and 460 women with and without preeclampsia. ABO blood groups were compared and associated factors for preeclampsia were determined.Results: Blood group O was significantly more common in early-onset and less common in late-onset preeclampsia. Regression analysis showed that blood group O decreased the risk of late-onset preeclampsia (aOR 0.63, 95%CI 0.42-0.93) but increased the risk of early-onset preeclampsia (aOR 1.97 95%CI 1.05-3.69).Conclusion: Blood group O decreased the risk of late-onset preeclampsia while it increased the risk of early-onset preeclampsia.     

A prospective cohort study of the value of maternal plasma concentrations of angiogenic and anti-angiogenic factors in early pregnancy and midtrimester in the identification of patients destined to develop preeclampsia

Objective.?Changes in the maternal plasma concentrations of angiogenic (placental growth factor (PlGF) and vascular endothelial growth factor (VEGF)) and anti-angiogenic factors (sEng and vascular endothelial growth factor receptor-1 (sVEGFR-1)) precede the clinical presentation of preeclampsia. This study was conducted to examine the role of maternal plasma PlGF, sEng, and sVEGFR-1 concentrations in early pregnancy and midtrimester in the identification of patients destined to develop preeclampsia.

Methods. This longitudinal cohort study included 1622 consecutive singleton pregnant women. Plasma samples were obtained in early pregnancy (6–15 weeks) and midtrimester (20–25 weeks). Maternal plasma PlGF, sEng, and sVEGFR-1 concentrations were determined using sensitive and specific immunoassays. The primary outcome was the development of preeclampsia. Secondary outcomes included term, preterm, and early-onset preeclampsia. Receiving operating characteristic curves, sensitivity, specificity, positive and negative likelihood ratios, and multivariable logistic regression were applied. A p-value of <0.05 was considered significant.

Results.?(1) The prevalence of preeclampsia, term, preterm, (<37 weeks) and early-onset preeclampsia (<34 weeks) was 3.8 (62/1622), 2.5 (40/1622), 1.4 (22/1622) and 0.6% (9/1622), respectively; (2) Higher likelihood ratios were provided by ratios of midtrimester plasma concentrations of PlGF, sEng, and sVEGFR-1 than single analytes; (3) Individual angiogenic and anti-angiogenic factors did not perform well in the identification of preeclampsia as a whole; in particular, they perform poorly in the prediction of term preeclampsia; (4) In contrast, a combination of these analytes such as the PlGF/sEng ratio, its delta and slope had the best predictive performance with a sensitivity of 100%, a specificity of 98–99%, and likelihood ratios for a positive test of 57.6, 55.6 and 89.6, respectively, for predicting early-onset preeclampsia.

Conclusions.?(1) The PlGF/sEng ratio and its delta and slope had an excellent predictive performance for the prediction of early-onset preeclampsia, with very high likelihood ratios for a positive test result and very low likelihood ratios for a negative test result; and (2) Although the positive likelihood ratios are high and the positive predictive values low, the number of patients needed to be closely followed is 4:1 for the PlGF/sEng ratio and 3:1 for the slope of PlGF/sEng.     

Maternal plasma concentrations of sST2 and angiogenic/anti-angiogenic factors in preeclampsia

Abstract

Objectives: Angiogenic/anti-angiogenic factors have emerged as one of the promising biomarkers for the prediction of preeclampsia. Since not all patients with preeclampsia can be identified by these analytes, the search for additional biomarkers continues. The soluble form of ST2 (sST2), a protein capable of binding to interleukin (IL)-33 and thus contributing to a Th1-biased immune response, has been reported to be elevated in maternal plasma of women with preeclampsia. The aims of this study were to examine: (1) differences in maternal plasma concentrations of sST2 and IL-33 between women diagnosed with preeclampsia and those having uncomplicated pregnancies; (2) the relationship between sST2, umbilical and uterine artery Doppler velocimetry, and the severity of preeclampsia; and (3) the performance of sST2 and angiogenic/anti-angiogenic factors in identifying patients with preeclampsia at the time of diagnosis.

Methods: This cross-sectional study included women with preeclampsia (n?=?106) and women with an uncomplicated pregnancy (n?=?131). Plasma concentrations of sST2, IL-33, soluble vascular endothelial growth factor receptor (sVEGFR)-1, soluble endoglin (sEng) and placental growth factor (PlGF) were determined by enzyme linked immune sorbent assay. Area under the receiver operating characteristic curve (AUC) for the identification of preeclampsia was examined for each analyte.

Results: (1) Patients with preeclampsia had a higher mean plasma concentrations of sST2 than those with an uncomplicated pregnancy (p?<?0.0001), while no significant difference in the mean plasma concentration of IL-33 between the two groups was observed; (2) the magnitude of this difference was greater in early-onset, compared to late-onset disease, and in severe compared to mild preeclampsia; (3) sST2 plasma concentrations did not correlate with the results of uterine or umbilical artery Doppler velocimetry (p?=?0.7 and p?=?1, respectively) among women with preeclampsia; (4) sST2 correlated positively with plasma concentrations of sVEGFR1-1 and sEng (Spearman’s Rho?=?0.72 and 0.63; each p?<?0.0001), and negatively with PlGF (Spearman’s Rho?=??0.56, p?<?0.0001); and (5) while the AUC achieved by sST2 and angiogenic/anti-angiogenic factors in identifying women with preeclampsia at the time of diagnosis were non-significantly different prior to term (<37 weeks of gestation), thereafter the AUC achieved by sST2 was significantly less than that achieved by angiogenic/anti-angiogenic factors.

Conclusions: Preeclampsia is associated with increased maternal plasma concentrations of sST2. The findings that sST2 concentrations do not correlate with uterine or umbilical artery Doppler velocimetry in women with preeclampsia suggest that elevated maternal plasma sST2 concentrations in preeclampsia are not related to the increased impedance to flow in the utero-placental circulation. The performance of sST2 in identifying preeclampsia at the time of diagnosis prior to 37 weeks of gestation was comparable to that of angiogenic/anti-angiogenic factors. It remains to be elucidated if an elevation of maternal plasma sST2 concentrations in pregnancy is specific to preeclampsia.