妊娠早期孕妇血清解整合素-金属蛋白酶12水平变化与妊娠结局

值为0.29,明显低于正常单胎孕妇,差异有统计学意义(P<0.05).结论 早孕期孕妇血清中ADAM 12-S水平随孕周增加而上升,可用于非整倍体常染色体异常的筛查,同时还可预测胎停育、异位妊娠等早期妊娠丢失;ADAM 12-S可作为产前筛查指标,建议在孕9～12周时进行.     

孕妇血清妊娠相关蛋白和金属蛋白酶12变化与胚停育的相关性

目的探讨孕早期血清妊娠相关蛋白-A(PAPP-A)和血清金属蛋白酶12(ADAM12)-S水平变化及其与胚停育的相关性。方法回顾性分析2007年6月至2009年6月就诊于温州市第二人民医院788例孕早期(6～13周)孕妇,应用全自动时间分辨荧光免疫分析法测定其血清中PAPP-A和ADAM12-S水平,并对测定结果及结局进行分析。结果 (1)孕6、7、8、9、10、11、12、13周孕妇血清PAPP-A的中位数分别为93.19、222.56、438.63、790.56、1388.98、2440.99、3266.46、4031.83mU/L。血清PAPP-A水平呈现出随孕周增加而逐渐上升的趋势,呈线型相关(r=0.964,P<0.05)。(2)孕6、7、8、9、10、11、12、13周孕妇血清ADAM12-S中位数分别为60.08、114.13、222.12、295.29、378.11、435.66、500.93、564.95μg/L。孕妇血清ADAM12-A的水平呈现出随孕周增加而逐渐上升趋势,呈线型相关(r=0.997,P<0.05)。(3)妊娠早期孕妇的血清PAPP-A水平与ADAM12-S的水平呈正相关(r=0.793,P<0.05)。(4)788例中正常单胎孕妇657例,胚胎停止发育者75例,胚停育者血清PAPP-A及ADAM12-S水平明显低于同孕周正常早孕妇女,两组间差异有统计学意义(P<0.05)。结论孕早期孕妇血清PAPP-A和ADAM12-S水平随孕周增加而上升,可能是预测胚胎停止发育的指标。     

解整合素-金属蛋白酶12作为子(癇)前期筛查标志物的初步研究

目的 初步评价孕中期血清解整合素-金属蛋白酶12(a disintegrin and metalloprotease 12,ADAM 12)可否作为子癇前期筛查的一种标志物. 方法 通过病例-对照研究,采用初步建立的间接竞争法ELISA检测100例子癇前期患者与200例正常妊娠妇女孕14～18周血清标本中的ADAM 12水平,将其转换成MoM值后比较其有无明显差异. 结果 正常孕妇孕14～18周血清ADAM 12中位数分别为680/μg/L、738 μg/L、801 μg/L、849μg/L和900/μg/L,子癇前期患者孕14～18周血清ADAM 12中位数分别为598μg/L、664 μg/L、729/μg/L、791 μg/L和839μg/L.子癇前期组患者血清ADAM 12 LogMoM平均值-0.05242,明显低于正常孕妇组血清ADAM 12 LogMoM平均值-0.003 68(P＜0.01). 结论 子癇前期组患者孕14～18周血清ADAM 12水平明显低于正常孕妇,孕中期血清ADAM 12可能作为子癇前期筛查的一种标志物.     

早发子痫前期血清T-钙粘蛋白水平与子宫动脉血流关系研究

目的探讨早发子痫前期血清T-钙粘蛋白(T-cadherin)水平与子宫动脉血流的关系。方法选择2017年7月至2018年1月于中国医科大学附属盛京医院门诊及住院检查的孕28~34周单胎妊娠孕妇77例,其中39例子痫前期孕妇为研究组,38例正常孕妇为对照组。采用酶联免疫吸附法(ELISA)检测两组孕妇血清T-cadherin水平,抽血当日行彩色多普勒超声检测两组孕妇的双侧子宫动脉搏动指数(PI)、阻力指数(RI)及收缩期与舒张期血流速度比值(S/D)。比较两组孕妇血清T-cadherin水平的差异及血清T-cadherin水平与子宫动脉血流各个指标间的相关性。记录研究组孕妇分娩时的孕周及新生儿体重,研究T-cadherin水平与妊娠结局的关系。结果研究组T-cadherin为(3.93±0.99)μg/L,低于对照组的(5.03±0.73)μg/L(P0.01)。研究组子宫动脉S/D、PI及RI值明显高于对照组(P0.01)。相关性分析显示,研究组血清T-cadherin水平与子宫动脉PI值间r=-0.715,P0.001,与子宫动脉RI值间r=-0.725,P0.001,与子宫动脉S/D值间r=-0.63,P0.001;对照组孕妇血清T-cadherin的水平与子宫动脉PI、RI及S/D之间无相关性(P0.05)。研究组孕妇血清T-cadherin的水平与分娩孕周之间r=0.605,P0.001,与新生儿体重之间r=0.671,P0.001。结论早发子痫前期患者血清T-cadherin与子宫动脉血流呈负相关,并与早发子痫前期发病有关,可能在子痫前期的发病中处于主导地位,且与疾病进展和妊娠结局相关。     

多胎妊娠孕中期减至双胎与初始双胎妊娠的妊娠结局比较

目的 探讨多胎妊娠孕妇孕中期行减胎术减至双胎后与初始双胎孕妇的妊娠结局比较.方法 选择2007年8月至2010年9月在山东大学附属省立医院妇产科门诊或住院、多胎妊娠孕妇567例,其中双胎妊娠孕妇478例为非减胎组;妊娠12周以后在本院实施孕中期减胎术(在超声引导下经腹的胎心内氯化钾注射法),由初始多胎减至双胎的孕妇89例为减胎组.减胎组孕妇中,初始三胎70例,初始四胎13例,初始五胎及以上6例.观察两组孕妇年龄、分娩孕周、妊娠并发症、新生儿出生体质量及新生儿结局.结果 (1)两组孕妇年龄及分娩孕周:非减胎组与减胎组孕妇平均年龄分别为(29.7±4.5)和(29.9±5.0)岁,两组比较,差异无统计学意义(P=0.755).非减胎组与减胎组孕妇平均分娩孕周分别为(35.3±3.9)和(34.4±6.3)周,两组比较,差异有统计学意义(P＜0.01).分娩孕周＜28周者(即流产)在非减胎组发生率为6.3％( 30/478),在减胎组为15.7％( 14/89),两组比较,差异有统计学意义(P=0.002).(2)两组妊娠并发症:子痫前期发生率在非减胎组及减胎组分别为8.2％ (39/478)和12.4％(11/89),两组比较,差异无统计学意义(P=0.199);妊娠期糖尿病发生率在非减胎组及减胎组分别为1.7％(8/478)和3.4％( 3/89),两组比较,差异无统计学意义(P =0.287).(3)两组新生儿情况:①非减胎组两个胎儿出生体质量差值＞400g的发生率为28.9％(138/478),减胎组为27.0％ (24/89),两组比较,差异无统计学意义(P=0.715).非减胎组两个胎儿出生体质量差值＞100g的发生率为75.1％(359/478),减胎组为75.3％(67/89),两组比较,差异无统计学意义(P =0.972).②非减胎组新生儿平均出生体质量为(2700 ±468)g,明显高于减胎组的(2352 ±602)g,两组比较,差异有统计学意义(P＜0.01).非减胎组＞孕36周+1 分娩的新生儿平均出生体质量为(2809 ±424)g,减胎组为(2707±506)g,两组比较,差异有统计学意义(P＜0.01).③减胎组及非减胎组＞28孕周分娩新生儿的死亡率分别为1.3％( 1/78)和2.2％( 10/448);减胎组及非减胎组新生儿患病率分别为3.8％ (3/78)和4.0％ (18/448),两组＞28孕周分娩的新生儿死亡率及患病率分别比较,差异均无统计学意义(P =0.588、0.943).结论 多胎妊娠减胎至双胎的妊娠结局较初始双胎者差,其流产率较高;多胎妊娠减胎后分娩孕周受初始胎儿数的影响,新生儿出生体重质量低于初始双胎.     

正常妊娠和妊娠高血压综合征妇女血清瘦素水平的动态检测

目的　动态检测正常妊娠、妊娠高血压综合征 (妊高征 )妇女血清瘦素水平的变化特点。方法　采用放射免疫法测定 40例正常非妊娠妇女 (对照组 )以及 5 0例正常妊娠和 14例妊高征妇女(观察组 )孕 16～ 2 0、2 4～ 2 8、3 2～ 3 6周及分娩前的血清瘦素水平及其新生儿的脐血瘦素水平 ,同时测量身高、体重、血压及胎盘重量。结果　 ( 1)随着孕周的增加 ,观察组妇女血清瘦素水平呈上升趋势 ,其中妊高征妇女血清瘦素水平为 ( 14 1± 2 2 )～ ( 2 5 4± 2 7) μg/L ,较正常妊娠妇女的 ( 13 4± 3 0 )～( 2 1 4± 3 7) μg/L明显上升 (P <0 0 1) ,并持续至妊娠结束 ,而正常妊娠妇女血清瘦素水平在孕 2 8～3 6周时上升明显 ,孕 2 8周前及孕 3 6周后上升缓慢。 ( 2 )体重、体重指数与血清瘦素水平的相关性分析结果显示 ,正常妊娠、对照组妇女均呈显著性正相关 (r =0 478～ 0 63 9,P <0 0 5或P <0 0 1) ,而妊高征妇女无显著相关性 (r=0 0 3 5～ 0 3 79,P >0 0 5 )。( 3 )收缩压、舒张压、平均动脉压与血清瘦素水平的相关性分析结果显示 ,正常妊娠、孕 2 0周前的妊高征及对照组妇女无显著相关性 (r=0 113～0 498,P >0 0 5 ) ,而妊高征妇女孕 2 0周后呈显著正相关 (r=0 63 9～ 0 85 2 ,P <0 0 5 )     

E2动态监测在预测早期先兆流产妊娠结局中的应用价值

目的探究动态监测雌二醇(E2)在预测早期先兆流产妊娠结局中的应用价值。方法选取2014年2月~12月我院收治的妊娠期单胎孕妇163例,根据妊娠结果将其分为继续妊娠组53例、妊娠失败组46例和正常妊娠组64例。通过化学发光免疫法则,定时对三组孕妇血清E2水平进行测定。结果妊娠第6周,继续妊娠组与妊娠失败组E2水平分别为(429.83±73.64)pg/m L和(391.96±86.87)pg/m L,明显低于正常妊娠组的(698.59±64.34)pg/m L,差异有统计学意义(P0.05);妊娠第7周,妊娠失败组E2水平低于继续妊娠组和正常妊娠组,差异有统计学意义(P0.05)。妊娠第8周,妊娠失败组E2水平仍低于继续妊娠组和正常妊娠组,差异有统计学意义(P0.05)。且继续妊娠组和正常妊娠组的E2水平随孕周增加而增加。结论动态监测E2在预测早期先兆流产妊娠结局中有应用意义,值得临床推广。     

多胎妊娠选择性减胎术的时机对妊娠结局的影响

目的 比较不同孕周实施减胎术后的妊娠结局,分析选择性减胎术(简称减胎术)的手术时机对妊娠结局的影响. 方法 选择2002年1月至2012年2月期间,在山东大学附属省立医院产科就诊的辅助生殖技术(assisted reproductive technology,ART)后妊娠的双(多)胎妊娠孕妇302例,其中减胎组为三胎和四胎妊娠孕妇152例,分别于妊娠12～13+6(91例)、14～15+6(32例)、16～24+6周(29例)接受了减胎术,对照组为ART后妊娠的双胎妊娠孕妇150例.手术方法采用超声引导下经腹胎儿心脏注射氯化钾.采用回顾性分析方法,记录分娩孕周和新生儿出生体重,观察妊娠期糖尿病和妊娠期高血压疾病的发病情况.采用t检验、单因素方差分析或x2检验进行统计学分析. 结果 减胎组流产率(14.5％,22/152)高于对照组(6.7％,10/150),差异有统计学意义(x2=4.857,P＜0.05);妊娠16～24+6周减胎组流产率(31.0％,9/29)分别高于妊娠12～13+6周减胎组(8.8％,8/91)和对照组,差异均有统计学意义(x2分别为7.212、12.749,P＜0.05);妊娠12～13+6和14～15+6周减胎组流产率(15.6％,5/32)分别与对照组比较,差异均无统计学意义(x2分别为0.370、1.739,P＞0.05).减胎组和对照组的平均分娩孕周分别为(36.9±1.8)周和(37.0±1.8)周,重体重儿出生体重分别为(2720.4±455.0)g和(2729.1±413.8)g、轻体重儿出生体重分别为(2409.2±412.6)g和(2416.2±436.8)g,差异均无统计学意义(t分别为 0.346、-0.163、-0.136,P＞0.05).减胎组和对照组妊娠28～34周分娩率分别为6.2％(8/130)和6.4％(9/140)、胎儿生长不均称发生率分别为12.3％(16/130)和11.4％(16/140)、妊娠期糖尿病发病率分别为3.1％(4/130)和2.1％(3/140),妊娠期高血压疾病发病率分别为11.5％(15/130)和8.6％(12/140),差异均无统计学意义(x2分别为0.009、0.050、0.659、0.010,P＞0.05). 结论 实施选择性减胎术将多胎妊娠减至双胎,术后存在流产风险.掌握适宜的手术时机,在妊娠16周前手术,能够存一定程度上降低流产率.     

检测妊娠区带蛋白临床意义的研究

采用血清妊娠区带蛋白（ＰＺＰ）单向免疫扩散法时７０８例正常妊娠孕妇，２０７例异常妊娠孕妇及１８８例妇科肿瘤患者进行测定。结果表明：正常妊娠孕妇血清ＰＺＰ含量在妊娠第５周即可测出，其含量随孕周的增加而增加，至妊娠４０周达高峰；先兆流产预后佳者，８１．５％分布在正常范围内；妊高征、胎儿宫内生长迟缓、无脑儿、异位妊娠时，ＰＺＰ多在正常范围内；５１．６％恶性葡萄胎患者血清ＰＺＰ含量低于正常范围，绒毛膜癌低值者占８０．０％，在妇科肿瘤中，卵巢癌患者血清ＰＺＰ明显高于卵巢瘤（Ｐ＜０．０１），子宫内膜癌和宫颈癌高于子宫肌瘤（Ｐ＜０．０１）。本研究认为，测定血清ＰＺＰ含量可作为判定先兆流产预后，鉴别滋养细胞肿瘤及妇科良恶性肿瘤的一项重要参考指标。     

孕酮测定在诊断停经6周内异位妊娠的价值探讨

目的:探讨血清孕酮水平测定在诊断停经6周内异位妊娠的价值.方法:检测71例异位妊娠患者(异位妊娠组)血清孕酮值,并以69例入院安胎成功的宫内早孕且停经6周内的患者(宫内妊娠组)血清孕酮值作为对照.结果:异位妊娠组血清孕酮明显低于宫内妊娠组(P<0.01),取异位妊娠组血清孕酮值第95百分位为截断值,P95=47.6 nmol/L,鉴别诊断停经6周内异位妊娠和宫内妊娠的敏感性94.4%,特异性97.1%.结论:血清孕酮水平对孕6周内异位妊娠与宫内早孕有良好的鉴别诊断价值.     

妊娠中、晚期血清瘦素、β-hCG及ADAM12水平的变化及其与子痫前期发生的关系

目的：探讨妊娠中、晚期妇女血清瘦素、人绒毛膜促性腺激素β亚单位（β-hCG）及解整合素-金属蛋白酶12（ADAM12）的水平变化及这些指标对子痫前期（PE）发生的预测价值。方法：选择2007年6月—2008年5月在福建省妇幼保健院定期产检和住院分娩的189例妊娠妇女,分别测定妊娠中期（20～24周）和妊娠晚期（30～34周）血清瘦素、β-hCG、ADAM12的浓度,其中25例发展为PE者为病例组,164例正常妊娠者为正常组。根据受试者工作特征（ROC）曲线确定预测界限值。结果：①妊娠中期病例组血清β-hCG、ADAM12浓度显著高于正常组（P＜0.001）。②妊娠晚期病例组血清瘦素、β-hCG、ADAM12浓度明显高于正常组（P＜0.001）。③病例组妊娠晚期血清瘦素、β-hCG及ADAM12水平均较妊娠中期升高（P＜0.05）,正常组妊娠晚期血清瘦素水平较妊娠中期升高（P＜0.001）, 而血清β-hCG与ADAM12水平2组间差异无统计学意义（P＞0.05）。④妊娠中期以血清β-hCG≥32 μg/L、血清ADAM12≥818 μg/L为预测界值,两者联合阳性预测值为82.61%,高于单项阳性预测值（P＜0.05）。两者联合ROC曲线下面积与单项ROC曲线下面积比较差异无统计学意义（P＞0.05）。⑤妊娠晚期以血清瘦素≥23 μg/L、血清β-hCG≥37 μg/L及血清ADAM12≥900 μg/L为预测界值,三者联合阳性预测值达92.31%,高于单项阳性预测值（P＜0.05）。三者联合ROC曲线下面积大于单项β-hCG及瘦素ROC曲线下面积（P＜0.05）,但与单项ADAM12曲线下面积差异无统计学意义（P＜0.05）。⑥联合妊娠中、晚期血清β-hCG预测PE发生的阳性率为81.25%;联合妊娠中、晚期血清ADAM12预测PE发生的阳性率为90.48%,均比单一指标的阳性预测值高。结论：检测妊娠中、晚期妇女血清β-hCG及ADAM12水平可作为PE发生的有效预测指标;联合多项指标并动态监测可进一步提高对PE发生的阳性预测值及准确率。     

妊娠中、晚期血清瘦素、β-hCG及ADAM12水平的变化及其与子痫前期发生的关系

目的：探讨妊娠中、晚期妇女血清瘦素、人绒毛膜促性腺激素β亚单位（β-hCG）及解整合素-金属蛋白酶12（ADAM12）的水平变化及这些指标对子痫前期（PE）发生的预测价值.方法：选择2007年6月-2008年5月在福建省妇幼保健院定期产检和住院分娩的189例妊娠妇女,分别测定妊娠中期（20～24周）和妊娠晚期（30～34周）血清瘦素、β-hCG、ADAM12的浓度,其中25例发展为PE者为病例组,164例正常妊娠者为正常组.根据受试者工作特征（ROC）曲线确定预测界限值.结果：①妊娠中期病例组血清β-hCG、ADAM12浓度显著高于正常组（P＜0.001）.②妊娠晚期病例组血清瘦素、β-hCG、ADAM12浓度明显高于正常组（P＜0.001）.③病例组妊娠晚期血清瘦素、β-hCG及ADAM12水平均较妊娠中期升高（P＜0.05）,正常组妊娠晚期血清瘦素水平较妊娠中期升高（P＜0.001）,而血清β-hCG与ADAM12水平2组间差异无统计学意义（P＞0.05）.④妊娠中期以血清β-hCG≥32 μg/L、血清ADAM12≥818 μg/L为预测界值,两者联合阳性预测值为82.61%,高于单项阳性预测值（P＜0.05）.两者联合ROC曲线下面积与单项ROC曲线下面积比较差异无统计学意义（P＞0.05）.⑤妊娠晚期以血清瘦素≥23 μg/L、血清β-hCG≥37 μg/L及血清ADAM12≥900 μg/L为预测界值,三者联合阳性预测值达92.31%,高于单项阳性预测值（P＜0.05）.三者联合ROC曲线下面积大于单项β-hCG及瘦素ROC曲线下面积（P＜0.05）,但与单项ADAM12曲线下面积差异无统计学意义（P＜0.05）.⑥联合妊娠中、晚期血清β-hCG预测PE发生的阳性率为81.25%;联合妊娠中、晚期血清ADAM12预测PE发生的阳性率为90.48%,均比单一指标的阳性预测值高.结论：检测妊娠中、晚期妇女血清β-hCG及ADAM12水平可作为PE发生的有效预测指标;联合多项指标并动态监测可进一步提高对PE发生的阳性预测值及准确率.     

ADAM12s in maternal serum as a potential marker of pre-eclampsia

OBJECTIVE: To examine whether maternal serum ADAM12s, a potential first- and second-trimester marker of fetal aneuploidy and fetal growth, had altered concentrations in the first or second trimester of pregnancies subsequently developing pre-eclampsia. METHODS: ADAM12s was measured by a time-resolved fluoroimmunoassay developed by PerkinElmer Life Science. Maternal serum samples from women taking part in early first-trimester aneuploidy screening in whom the pregnancy resulted in pre-eclampsia (64) were identified from a cohort of 4,390 singleton pregnancies in which uterine artery Doppler mean Pulsatility Index (PI) had been measured at 22-24 weeks. From amongst those cases delivering a normal term infant with birth weight greater than the 10th centile for gestational age 240 cases were selected as gestational age-matched controls. A second study group consisting of maternal serum taken at 22-24 weeks at the time of uterine artery Doppler in a group of 12 women developing pre-eclampsia were compared with 86 matched controls from a previously studied cohort of 24 cases and 144 controls. Serum ADAM12s concentrations were converted to multiple of the median (MoM) to take account of gestational age variation. RESULTS: First-trimester maternal serum ADAM12s levels in women who developed pre-eclampsia were reduced with a median MoM of 0.71 which was further reduced in those delivering prior to 35 weeks (0.50). At the 5th centile of normal (0.48 MoM) ADAM12s identified 27% of cases with pre-eclampsia and 47% of those with early pre-eclampsia. Combining ADAM12s with PAPP-A from a previous study only resulted in a further 1% increase in detection of all women developing pre-eclampsia. However combining ADAM12s with mean PI increased the detection rate to 66%. In the second trimester at 22-24 weeks the maternal serum ADAM12s levels were increased in those women developing pre-eclampsia compared to controls (709 vs 486 ug/L, p = 0.045). CONCLUSION: ADAM12s in addition to being a potential marker of aneuploidy may also be a marker of pre-eclampsia. Further studies are required to see if this can improve on the clinical discrimination already provided by PAPP-A in the early first trimester.     

ADAM12: a novel first-trimester maternal serum marker for Down syndrome

OBJECTIVES: The concentration of bioavailable insulin-like growth factor (IGF) I and II is important to foetal growth. It is regulated by insulin-like growth factor binding proteins (IGFBP) 1 through 6. Proteolytic cleavage of IGFBP-3 takes place in human pregnancy serum; accordingly, IGFBP-3 serum levels decrease markedly during pregnancy. ADAM12 (A disintegrin and metalloprotease) is an IGFBP-3 and IGFBP-5 protease and is present in human pregnancy serum. The goal of this study was to determine whether ADAM12 concentration in maternal serum is a useful indicator of foetal health. METHODS: We developed an enzyme-linked immunosorbent assay (ELISA) for the quantification of ADAM12 in serum. The assay range was 42 to 667 micro g/L. Recombinant ADAM12 was used as the standard for calibration. RESULTS: We found that ADAM12 was highly stable in serum. Serum concentration increased from 180 micro g/L at week 8 of pregnancy to 670 micro g/L at 16 weeks, and reached 12 000 micro g/L at term. In 18 first-trimester Down syndrome pregnancies, the concentration of ADAM12 was decreased, thus the median multiple of mean (MoM) value was 0.14 (0.01-0.76). A detection rate for foetal Down syndrome of 82% for a screen-positive rate of 3.2% and a 1:400 risk cut-off was found by Monte Carlo estimation using ADAM12 and maternal age as screening markers. CONCLUSION: ADAM12 is a promising marker for Down syndrome.     

The level of ADAM12-S in maternal serum is an early first-trimester marker of fetal trisomy 18

BACKGROUND: ADAM12-S is a pregnancy-associated insulin-like growth factor binding protein-3 (IGFBP-3) and IGFBP-5 protease present in human gestational serum. Recently, maternal serum levels of ADAM12-S were found to be markedly reduced during the first trimester of pregnancies with a Down syndrome (DS) fetus. On the basis of this finding, it was suggested that ADAM12-S might be a useful maternal serum marker of fetal chromosomal disease. OBJECTIVE: Retrospective examination of the use of ADAM12-S as a marker for fetal trisomy 18. METHOD: Serum samples were obtained from ten women during the first semester of their pregnancies with fetuses that had trisomy 18. An ELISA was used to determine the levels of ADAM12 in maternal serum. Results were compared to ADAM12-S levels, previously measured in the serum of 170 women carrying normal pregnancies during the first trimester. RESULTS: In all cases, the ADAM12-S concentration in maternal serum samples was lower in trisomy 18 pregnancies than in normal pregnancies, with a median multiple of the median (MoM) of 0.28 (p < 0.001) CONCLUSION: A reduced concentration of ADAM12-S in maternal serum is a promising marker for foetal trisomy 18, as well as for DS.     

Reduction of the disintegrin and metalloprotease ADAM12 in preeclampsia

OBJECTIVES: The secreted form of ADAM12 is a metalloprotease that may be involved in placental and fetal growth. We examined whether the concentration of ADAM12 in first-trimester maternal serum could be used as a marker for preeclampsia. METHODS: We developed a semiautomated, time-resolved, immunofluorometric assay for the quantification of ADAM12 in serum. The assay detected ADAM12 in a range of 78-1248 microg/L. Serum samples derived from women in the first trimester of a normal pregnancy (n = 324) and from women who later developed preeclampsia during pregnancy (n = 160) were obtained from the First Trimester Copenhagen Study. ADAM12 levels were assayed in these serum samples. Serum levels of ADAM12 were converted to multiples of the median (MoM) after log-linear regression of concentration versus gestational age. RESULTS: Serum ADAM12 levels in women who developed preeclampsia during pregnancy had a mean log MoM of -0.066, which was significantly lower than the mean log MoM of -0.001 for ADAM12 levels observed in serum samples from women with normal pregnancy (P = .008). The mean log MoM was even lower in serum derived from preeclamptic women whose infant's weight at birth was less than 2,500 g (n = 27, mean log MoM of -0.120, P = .053). CONCLUSION: The maternal serum levels of ADAM12 are significantly lower during the first trimester in women who later develop preeclampsia during pregnancy when compared with levels in women with normal pregnancies. Because the secreted form of ADAM12 cleaves insulin-like growth factor binding protein (IGFBP)-3 and IGFBP-5, the IGF axis may play a role in preeclampsia. ADAM12 may be a useful early marker for preeclampsia. LEVEL OF EVIDENCE: II-2.     

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。     

糖代谢异常孕妇体质量及相关因素对新生儿出生体质量的影响

目的 探讨影响糖代谢异常孕妇新生儿出生体质量的相关因素.方法 选择2005年1月-2009年12月在北京大学第一医院分娩的临床资料齐全的妊娠合并糖代谢异常足月单胎孕妇1157例,根据孕前体质指数(BMI)分成4组:53例BMI＜18.5 kg/m2为低体质量组,647例BMI18.5～23.9 kg/m2为理想体质量组,323例BMI 24.0～27.9 kg/m2为超体质量组,134例BMI≥28.0 kg/m2为肥胖组.1157例新生儿按出生体质量分为:出生体质量2500～4000 g为正常体质量儿(987例),其中545例出生体质量3000～3500 g为适宜体质量儿;出生体质量≥4000 g为巨大儿(112例);出生体质量＜2500 g为低体质量儿(58例).记录其孕前体质量、身高、糖代谢异常诊断时间及诊断时体质量、孕期血脂水平、不良产史、糖尿病家族史、分娩孕周、分娩时体质量、新生儿出生体质量.分析孕前BMI、孕期体质量增长(分娩时体质量-孕前体质量)、诊断糖代谢异常的孕周、诊断后孕妇体质量增长(分娩时体质量-诊断糖代谢异常时体质量)、孕期血脂水平、不良产史及糖尿病家族史对新生儿出生体质量的影响及计算孕前不同BMI孕妇分娩适宜体质量儿的孕期体质量适宜增长范围.结果 (1)新生儿平均出生体质量:低体质量组为(3142±333)g,理想体质量组为(3339±476)g,超体质量组为(3381±581)g,肥胖组为(3368±644)g.新生儿出生体质量随孕前BMI增加而增加,低体质量组新生儿平均出生体质量低于其他3组,分别比较,差异均有统计学意义(P＜0.05);但理想体质量组、超体质量组、肥胖组间分别比较,差异均无统计学意义(P＞0.05).(2)分娩正常体质量儿和巨大儿孕妇的孕期体质量增长:分娩正常体质量儿及分娩巨大儿的各组孕妇孕期体质量增长为,理想体质量组分别为(13.5±4.5)及(17.1±5.4)kg,超体质量组分别为(11.6±4.9)及(15.3±6.4)kg,肥胖组分别为(10.3±5.0)及(14.7±7.4)kg,3组分别比较,差异均有统计学意义(P＜0.05);低体质量组分娩巨大儿的孕妇仅1例,无法进行统计学分析.(3)分娩正常体质量儿和巨大儿孕妇的糖代谢异常诊断孕周:理想体质量组分别为(27.8±5.8)及(29.8±5.3)周,超体质量组分别为(26.7±6.8)及(30.2±4.1)周,两者分别组内比较,差异均有统计学意义(P＜0.05);肥胖组分别为(26.2±7.5)及(25.7±9.3)周,差异无统计学意义(P＞0.01);低体质量组分娩巨大儿孕妇例数仅1例,无法进行统计学分析.(4)分娩正常体质量儿与巨大儿孕妇的血脂水平:分娩巨大儿孕妇血清甘油三酯水平[(3.1±1.5)mmol/L]明显高于分娩正常体质量儿的孕妇[(2.7±1.2)mmol/L,P＜0.01];分娩巨大儿孕妇血清高密度脂蛋白胆固醇水平[(1.4±0.3)mmol/L]明显低于分娩正常体质量儿的孕妇[(1.7±0.9)mmol/L,P＜0.05];分娩巨大儿孕妇血清低密度脂蛋白胆固醇及总胆固醇水平[分别为(2.8±0.8)及(5.4±1.1)mmol/L]均低于分娩正常体质量儿的孕妇[分别为(3.0±0.9)及(5.6±1.1)mmol/L],但差异无统计学意义(P＞0.05).(5)影响新生儿出生体质量的相关因素:将年龄、不良产史、糖尿病家族史、孕前BMI、孕期体质量增长、诊断糖代谢异常后孕妇体质量增长、孕期血脂水平、糖代谢异常分类、诊断孕周等因素进行logistic多元回归模型分析,最终进入回归模型的变量中排在前3位的是孕前BMI、孕期体质量增长及高密度脂蛋白胆固醇水平(P＜0.01).结论 妊娠合并糖代谢异常孕妇新生儿出生体质量与孕前BMI、孕期体质量增长、孕期血浆高密度脂蛋白胆固醇水平相关.