子痫前期与代谢组学

<正>子痫前期(preeclampsia,PE)是妊娠期妇女特有的疾病,发病率高达3%,常伴有严重的母婴并发症,是导致孕妇死亡的主要原因[1]。子痫前期是以妊娠中期出现高血压和蛋白尿为特征,分为早发型(34周之前)和晚发型(34周后)子痫前期[2]。子痫前期的发病机制迄今尚未完全阐明,目前认为该病始发于妊娠早期,引起胎盘血管发育障碍,导致胎盘的浅着床、氧化应激及系统性炎症反     

妊娠期高血压疾病患者胎盘组织中溶血磷脂酸受体蛋白Edg4、7的表达及其意义

目的 探讨胎盘组织中溶血磷脂酸受体蛋白Edg4、7的表达与妊娠期高血压疾病发生的关系及作用机制。方法 采用免疫组化链霉菌抗生物素蛋白-过氧化物酶（SP）法,检测20例正常晚期妊娠妇女（正常晚孕组）、20例妊娠期高血压患者（妊娠期高血压组）、20例轻度子痫前期患者（轻度子痫前期组）、30例重度子痫前期患者（重度子痫前期组）的胎盘组织中溶血磷脂酸受体蛋白Edg4与Edg7的表达。结果（1）表达部位：Edg4与Edg7主要表达于胎盘绒毛滋养细胞及蜕膜细胞的细胞质和细胞膜。（2）Edg4和Edg7在胎盘绒毛滋养细胞中的表达阳性率：正常晚孕组分别为25％和20％,妊娠期高血压组分别为60％和40％,轻度子痫前期组分别为80％和65％,重度子痫前期组分别为83．3％和86,7％。轻、重度子痫前期组阳性率明显高于正常晚孕组,两组分别比较,差异有统计学意义（P〈0,05）;妊娠期高血压组与正常晚孕妇组比较,差异无统计学意义（P〉0．05）。（3）Edg4和Edg7在胎盘蜕膜细胞中的表达阳性率：正常晚孕组分别为20％和25％,妊娠期高血压组分别为55％和50％,轻度子痫前期组分别为70％和55％,重度子痫前期组分别为83．3％和73．3％。轻度子痫前期组及重度子痫前期组阳性表达率明显高于正常晚孕组,两组分别比较,差异有统计学意义（P〈0．05）;妊娠期高血压组与正常晚孕组比较,差异无统计学意义（P〉0．05）。结论 妊娠期高血压疾病患者胎盘组织中溶血磷脂酸受体蛋白Edg4、7呈高表达,提示溶血磷脂酸与胎盘组织中的特异性受体Edg4、7结合,并参与了妊娠期高血压疾病的发生。     

长链脂肪酸氧化酶mRNA在正常妊娠及重度子痫前期胎盘中的表达

目的研究长链羟酰基辅酶A脱氢酶(long-chain3-hydroxyacyl-CoAdehydrogenase,LCHAD)在正常妊娠不同孕期绒毛或胎盘组织的表达情况以及在伴有肝脏损害和不伴有肝脏损害重度子痫前期胎盘的表达差异。方法应用原位杂交和RT-PCR方法对早孕绒毛组织(10例)、妊娠中期胎盘组织(10例)、正常妊娠晚期胎盘组织(10例)及32例重度子痫前期胎盘组织进行LCHAD基因的定位表达及半定量测定。结果原位杂交实验显示正常妊娠早、中、晚期绒毛或胎盘组织及重度子痫前期胎盘组织滋养细胞中存在LCHAD阳性表达。RT-PCR实验显示①妊娠早期绒毛LCHAD表达与妊娠中期比较,P=0.844;妊娠早期绒毛LCHAD表达高于晚期胎盘,P=0.020;妊娠中期胎盘LCHAD表达也高于晚期胎盘P=0.026;②发病孕周≤34周早发型重度子痫前期伴肝损害胎盘组织中LCHAD表达均值为(0.449±0.038),不伴肝损害LCHAD表达均值为(0.482±0.042),伴肝损害较不伴肝损害者表达有减弱,但两组比较,P=0.084;发病孕周≤34周早发型重度子痫前期伴肝损害LCHAD表达量与正常晚期比较,P=0.05,而不伴肝损害重度子痫前期LCHAD表达量与正常晚期比较,P=0.775。结论本研究显示在妊娠的早中晚期滋养细胞中均存在长链脂肪酸氧化代谢,妊娠早中期LCHAD的mRNA表达高于妊娠晚期;早发型重度子痫前期伴肝损害胎盘组织中LCHAD表达均值与不伴有肝损害者比较虽无统计学差异,但是有明显降低趋势。提示长链脂肪酸氧化代谢对子痫前期伴发肝脏损害的影响还有待酶活性和蛋白水平以及代谢调节方面的深入研究。     

胎盘生长因子与子痫前期发病及一氧化氮关系的研究

目的:探讨胎盘生长因子(PLGF)在子痫前期发病中的作用及其与一氧化氮的关系。方法:选择妊娠期高血压疾病患者45例,其中妊娠期高血压10例,轻度子痫前期12例,重度23例;选择同期正常妊娠妇女20例作为对照组。采用免疫组织化学染色法和逆转录-聚合酶链式反应(RT-PCR)检测两组患者胎盘PLGF蛋白及mRNA的表达。采用硝酸盐还原酶法测定两组胎盘组织NO浓度的变化。结果:(1)免疫组化结果显示,轻度和重度子痫前期的胎盘绒毛合体滋养细胞、绒毛间质PLGF表达均显著低于正常妊娠组(P<0.05),妊娠期高血压组与正常组无差别;PLGF在妊娠期高血压、子痫前期组及正常妊娠组分布范围基本一致,主要分布在绒毛合体滋养细胞和间质细胞胞浆,部分血管合体膜上也有表达;(2)轻、重度子痫前期胎盘组织PLGF mRNA平均灰度分别为3.33±0.39、1.97±0.29,显著低于正常妊娠组的平均灰度4.87±0.60(P<0.01);(3)轻、重度子痫前期胎盘组织中NO浓度分别为8.20±5.56μmol/g、6.46±2.25μmol/g,显著低于对照组18.10±7.12μmol/g(P<0.05);妊娠期高血压组胎盘组织NO浓度与对照组差异无显著性;(4)胎盘组织中胎盘生长因子表达水平与胎盘组织NO浓度呈显著正相关(r=0.54,P<0.05)。结论:子痫前期胎盘组织中胎盘生长因子水平降低,NO浓度下降,可能在子痫前期的发病中起一定作用。     

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.     

妊娠期高血压疾病剖宫产孕妇再次妊娠发生早发型子痫前期的临床分析

目的 分析既往因妊娠期高血压疾病剖宫产孕妇再次妊娠发生早发型子痫前期的危险因素及母儿围产期结局.方法 收集2017年1月至12月来自11家三级医院既往因妊娠期高血压疾病剖宫产后再次妊娠的478例孕妇的临床资料,采用Logistic多因素回归分析方法,分析既往高血压类型和再次妊娠的临床特征与早发型子痫前期的相关性,以及早...     

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.     

早发型和晚发型重度子痫前期分娩方式及母婴结局分析

目的探讨早发型和晚发型重度子痫前期分娩方式及母婴结局。方法收集1977-2010年在西安交通大学医学院第一附属医院产科住院的重度子痫前期患者4457例,其中早发型860例,晚发型3597例。回顾性分析其分娩方式及母婴结局。结果早发型和晚发型重度子痫前期剖宫产率分别为57.7%和36.9%,早发型明显高于晚发型(P=0.02);胎盘早剥是最常见并发症,在早发型和晚发型重度子痫前期发生率分别为6.7%和4.6%(P<0.05)。早发型和晚发型重度子痫前期围生儿死亡率分别为3.6%和2.2%(P<0.01)。特别是早发型妊娠34周前终止妊娠者,围生儿死亡率高达4.9%。结论子痫前期终止妊娠的主要方式为剖宫产术;发病孕周越早,母婴不良结局发生率越高。     

早发型重度子痫前期妊娠结局分析

目的:探讨早发型重度子痫前期的临床特点及围生结局。方法:回顾性分析2006年6月至2009年6月四川大学华西第二医院收治的重度子痫前期患者413例,以发病孕周34周为界限,分为早发型重度子痫前期组156例(早发型组)及晚发型重度子痫前期组257例(晚发型组)。比较两组一般情况、并发症、分娩方式及围生儿结局等指标。结果:早发型组患者在终止妊娠孕周、延长孕周时间、住院时间、入院时血压、24小时尿蛋白、并发症发生率及围生儿结局等方面与晚发型组比较,差异均有高度统计学意义(P<0.01)。结论:早发型重度子痫前期患者病情严重,围生儿预后不佳,应根据母胎情况,适时剖宫产终止妊娠。     

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.     

早孕期（8~12周）血清D-二聚体、纤维蛋白原和妊娠相关蛋白A单独与联合预测稽留流产的效能#br#

Objective?To investigate the efficiencies of serum D-dimer (D-D), fibrinogen (Fib), pregnancy-associated plasma protein-A (PAPP-A) alone and in combination to predict missed abortion in early pregnancy (8~12 weeks). Methods?A total of 170 puerperae were selected as the research objects to compare the levels of DD, Fib and pregnancy-related protein A during the first trimester (8~12 weeks) of puerperae with different pregnancy outcomes. Results?During the first pregnancy examination, the serum DD in the missed abortion group and the threatened abortion group was significantly higher than that in the normal pregnancy group, and Fib and pregnancy-related protein A were significantly lower than those in the normal pregnancy group (P<0.05), significantly lower than the threatened abortion group (P<0.05). The areas under the curve of serum DD, Fib and pregnancy-related protein A for predicting missed abortion were 0.761, 0.828 and 0.721, respectively, and the combined prediction area of the three was 0.923, with sensitivity and specificity up to 91.72% and 81.53%. Conclusion?Combination of serum D-D, Fib and PAPP-A can improve the predictive efficiency and early diagnosis rate of missed abortion.     

The Prognostic Value of HCG, PAPP-A, Oestradiol-170 and Progesterone in Early Human Pregnancy

Four serum parameters were assayed weekly from the 4th to the 12th week of pregnancy and finally at 16 weeks, to assess their relative prognostic values for predicting pregnancy outcome. Of 85 pregnancies generated following treatment for infertility, 16 cases had blighted ova and subsequently aborted at a mean age of 9.9 +/- 0.5 weeks. Serum HCG concentrations differentiated (p less than 0.005) between ongoing pregnancies and blighted ova as early as the 4th week which was often several weeks in advance of clinical abortion. PAPP-A, oestradiol-17 beta and progesterone did not differentiate between the 2 groups until 7 weeks (p less than 0.005, p less than 0.001 and p less than 0.001 respectively). PAPP-A measurements detected ongoing pregnancies at week 4 (16.5 +/- 5 micrograms/l) but HCG remains the more sensitive diagnostic test. The lower limits of oestradiol-17 beta and progesterone for ongoing pregnancies were 670 pmol/l and 37 nmol/l respectively. The circulating concentrations of all 4 serum markers were unaffected by administration of medroxyprogesterone acetate from 6 to 16 weeks in both ongoing and aborting pregnancies.     

妊娠期高血压疾病胎儿纤维连接蛋白及人绒毛膜促性腺激素的定量变化

目的探讨妊娠期高血压疾病(HDCP)中胎儿纤维连接蛋白(fetal fibronectin,FFN)及血清人绒毛膜促性腺激素(β-HCG)定量的变化,为临床治疗提供更有效的试验依据。方法 2010年1月至2011年1月在中山大学附属中山市人民医院利用前瞻性对照研究方法,采用酶联免疫吸附法检测妊娠期高血压疾病组(HDCP组38例,其中妊娠期高血压患者12例,轻度子痫前期患者15例,重度子痫前期患者11例)及正常妊娠组(45例)孕16～20周、24～28周、32～36周时FFN及血β-HCG定量。对照组(健康未孕的育龄期女性50例)于常规检查时抽血检测以上两值。结果对照组FFN均值为(225±76)mg/L;正常妊娠组在孕20周前与对照组比较FFN差异无统计学意义(P>0.05);孕24周后比较FFN差异有统计学意义(P<0.05),且有随孕周增加而逐渐升高的趋势;HD-CP组与对照组及同孕周正常妊娠组比较FFN差异均有统计学意义(P<0.05),且与病情进展程度及孕周增加情况呈一致性。对照组血β-HCG均为0;HDCP组中血β-HCG定量与同孕周正常妊娠组比较,孕16～20周时差异无统计学意义(P>0.05),孕24周后差异有统计学意义(P<0.05),且与病情进展程度及孕周增加情况呈一致性。结论孕早期孕妇联合检测FFN及血β-HCG定量对HDCP特别是重度子痫前期具有重要的预测价值,并可减少子痫前期的发生率。     

Predicting complications of pregnancy with first-trimester maternal serum free-betahCG, PAPP-A and inhibin-A

OBJECTIVE: To find whether fbetahCG, PAPP-A and inhibin-A levels in maternal serum or fetal nuchal translucency (NT) thickness at the first-trimester screening for trisomy 21 (T21) might detect women at high risk for adverse pregnancy outcomes. METHODS: A retrospective analysis of 1136 women with singleton pregnancy between 10 and 14 weeks. Women with pregnancy complications were allotted to five subgroups: small for gestational age (SGA), large for gestational age (LGA), gestational diabetes (GDM), hypertensive disorders, preterm delivery; women with normal pregnancy represented the control group. NT, maternal serum fbetahCG, PAPP-A and inhibin-A were measured. Mann-Whitney test was used for the comparison of fbetahCG, PAPP-A, inhibin-A and NT between a subgroup of a certain pregnancy complication and the control group. Multivariate logistic regression models were built to explore the relationship among different variables and the occurrence of pregnancy complications. RESULTS: PAPP-A values were significantly lower in women who delivered SGA babies (n=51, 0.76 MoM; p=0.002) and significantly higher in women who delivered LGA babies (n=120, 1.12 MoM; p=0.036). In women with GDM (n=27), fbetahCG, PAPP-A and inhibin-A were insignificantly lower than in controls, whereas in women with hypertensive disorders (n=56) no significant differences between the groups were found. In women with a preterm delivery (<34 weeks) (n=17), inhibin-A levels were significantly higher (1.25 MoM; p=0.015). CONCLUSION: Low PAPP-A level is associated with the delivery of an SGA baby and high PAPP-A with the delivery of an LGA baby. High inhibin-A is associated with preterm delivery before 34 weeks. Feto-placental products in the first trimester do not prove to be useful as a screening tool for predicting pregnancy complications.     

VCAM-1和PAPP-A在妊娠期高血压疾病患者中的表达及其相关性研究

目的:研究血管细胞黏附分子-1(VCAM-1)和妊娠相关血浆蛋白-A(PAPP-A)在妊娠期高血压疾病患者血清中的变化及在胎盘组织中的表达情况,探讨与妊娠期高血压疾病发病机制的关系。方法:收集2009年3月至2011年6月我院确诊为妊娠期高血压疾病的120例孕妇为实验组,正常孕妇40例为对照组。采用酶联免疫吸附法(ELISA)测定两组孕妇血清中VCAM-1和PAPP-A水平变化并进行比较。采用免疫组织化学染色方法检测VCAM-1和PAPP-A在两组胎盘组织中的表达。结果:①实验组VCAM-1和PAPP-A血清水平明显高于对照组,差异有统计学意义(P<0.05)。②VCAM-1在实验组胎盘组织中阳性表达较对照组减弱,差异有统计学意义(P<0.05)。PAPP-A在实验组胎盘组织中阳性表达较对照组明显增强,差异有统计学意义(P<0.05)。③实验组中血清VCAM-1、PAPP-A表达呈明显正相关(r=0.713,P<0.05),实验组胎盘免疫组化VCAM-1、PAPP-A表达呈负相关(r=-0.513,P<0.05)。结论:VCAM-1和PAPP-A在孕期母血清及胎盘组织中的改变与妊娠期高血压疾病的发病有明确关系。     

孕早期血清PAPP-A水平与妊娠和围产结局的关系

目的:探讨孕早期血清妊娠相关蛋白-A(pregnancy associatied plasma protein A,PAPP-A)水平对妊娠和围产结局的预测价值。方法:对664例孕4~14周初产妇采用酶联免疫法检测血清PAPP-A水平,并随访该人群至妊娠终止或分娩,分析孕早期血清PAPP-A水平与妊娠和围产结局的关系。结果:①664例初产妇女中,随访到妊娠结局的420例,其中异常妊娠(自然流产、胚胎停止发育)35例(8.33%),建立苏州市围产保健册并成功分娩的385例(91.67%)。②早孕妇女血清PAPP-A水平随孕周的增加而升高。③妊娠结局为异常妊娠的妇女其孕早期血清PAPP-A的中位数倍数值(multiples of the respective normal median,MOM值)水平低于成功分娩者(P<0.05)。④成功分娩孕妇的孕早期血清PAPP-A的MOM值与其早孕期体质量、体质量指数(body mass index,BMI)呈负相关(分别为-0.156,-0.159),与年龄、身高无相关性(P>0.05)。⑤孕早期血清PAPP-A的MOM值与其胎儿性别、出生体质量和分娩方式等无相关性(P>0.05)。结论:孕早期血清PAPP-A水平低常预示早期不良妊娠结局;成功分娩妇女早孕血清PAPP-A水平与其早孕期体质量、BMI呈负相关,但不能预测围产结局。     

The secretion of PAPP-A, ADAM12, and PP13 correlates with the size of the placenta for the first month of pregnancy

Objectives

Pregnancy Associated Protein A (PAPP-A), A Disintegrin and Metalloproteinase 12 (ADAM12) and Placental Protein 13 (PP13) are secreted from the placental trophoblastic tissue and are involved in normal implantation and placental development. The aim of the study was to assess the connection between the secretion of these proteins and the growth of the gestational sac and the placenta.

Study design

In an observational longitudinal study at Oulu University Hospital, women with naturally conceived pregnancies were followed-up weekly to pregnancy week 11.

Main outcome measures

PAPP-A, ADAM12 and PP13 serum concentrations and their correlation with the volumes of the gestational sac and the placenta were assessed using three-dimensional ultrasonography.

Results

The study group consisted of 41 women. The PAPP-A, ADAM12 and PP13 serum concentrations increased continuously from pregnancy week 4 to week 11 and correlated closely with each other. The serum concentrations of PAPP-A, ADAM12 and PP13 also correlated with the volumes of the gestational sac and the placenta up to pregnancy week 8.

Conclusions

The secretion of PAPP-A, ADAM12 and PP13 is closely related to the size of the placenta in the beginning of pregnancy. After 8 weeks of pregnancy, which is the time for luteoplacental shift, the correlation disappears, possibly reflecting the morphologic transformation in the placenta.     

First trimester maternal serum free beta human chorionic gonadotrophin and pregnancy associated plasma protein A as predictors of pregnancy complications

Objective To examine the value of first trimester maternal serum free β human chorionic gonadotrophin (β hCG) and pregnancy associated plasma protein A (PAPP-A) as predictors of pregnancy complications.
Design Screening study.
Setting Antenatal clinics.
Population Singleton pregnancies at 10–14 weeks of gestation.
Methods Maternal serum free β hCG and PAPP-A were measured at 10–14 weeks of gestation in 5584 singleton pregnancies. In the 5297 (94.9%) pregnancies with complete follow up free β hCG and PAPP-A were compared between those with normal outcome and those resulting in miscarriage, spontaneous preterm delivery, pregnancy induced hypertension or fetal growth restriction and in those with pre-existing or gestational diabetes.
Results Maternal serum PAPP-A increased and β hCG decreased with gestation. The multiple of median maternal serum PAPP-A was significantly lower in those pregnancies resulting in miscarriage, pregnancy induced hypertension, growth restriction and in those with pre-existing or gestational diabetes mellitus, but not in those complicated by spontaneous preterm delivery. The level was < 10th centile of the reference range in about 20% of the pregnancies that subsequently resulted in miscarriage or developed pregnancy induced hypertension or growth restriction, and in 27% of those that developed gestational diabetes. Maternal serum free β hCG was < 10th centile of the reference range in about 15% of the pregnancies that subsequently resulted in miscarriage or developed pregnancy induced hypertension or growth restriction, and in 20% of those that developed gestational diabetes.
Conclusion Low maternal serum PAPP-A or β hCG at 10–14 weeks of gestation are associated with subsequent development of pregnancy complications.     

妊娠期孕妇血清TTR水平变化及其用于诊断子痫前期的价值

目的:观察正常妊娠人群血清中转甲状腺素蛋白(TTR)浓度在孕期的变化,探讨血清TTR浓度在子痫前期诊断和监测病情中的价值。方法:(1)无并发症及合并症的正常妇女62例,分别于孕前、孕12~16周、20~24周、28~32周和37~41周留取静脉血清。(2)无产科并发症及内外科合并症正常孕妇50例作为对照组,诊断为妊娠期高血压疾病的孕妇分为重度子痫前期组(SPE组,30例)和妊娠期高血压、妊娠合并慢性高血压及轻度子痫前期组(GHD组,49例)。SPE组和GHD组分别于诊断时留取静脉血清,对照组分别在相应孕周留取外周静脉血清。ELISA法测定血清TTR浓度。结果:正常妇女TTR血清水平:孕前(245.65±5.02)mg/L,孕12~16周、20~24周、28~32周和37~41周血清TTR浓度分别为(649.86±43.40)mg/L、(856.10±52.28)mg/L、(410.04±22.82)mg/L、(413.71±24.17)mg/L。SPE组孕妇血清TTR浓度[(86.58±10.23)mg/L]显著低于对照组[(411.64±25.80)mg/L]及GHD组[(468.59±42.93)mg/L](P0.05);GHD组与对照组比较差异无统计学意义(P0.05)。结论:TTR血浆浓度在未孕时最低,随孕周增加逐渐升高,孕20~24周时达高峰,之后快速下降,到孕晚期与孕早期持平。TTR在监测病情变化及对治疗反应方面可能有一定的意义。     

Fluctuations in pregnancy-associated protein A (PAPP-A) levels in the sera of pregnant women

Pregnant serum PAPP-A, SP1 and HPL concentration were measured in 188 normal pregnant sera, 43 pathological sera by Laurell's method for PAPP-A and HPL, by SRID method for SP1. PAPP-A was detected from about 10 weeks of gestational age. Throughout the pregnancy, PAPP-A concentration correlated to gestational age significantly (r = 0.773), while the correlation was not observed in late pregnancy. In normal pregnancy, PAPP-A concentration correlated to both SP1 and HPL concentration through all gestational age significantly. In abnormal pregnancy, however, PAPP-A concentration increased in severe toxemia and IUGR against decreasing SP1 and HPL concentrations. So far as twin pregnancy and hydramnion, PAPP-A, SP1 and HPL concentrations increased together. These results indicate that PAPP-A concentration may reflect feto-placental function in normal pregnancy and predict some obstetric disorders.