妊娠肝内胆汁淤积症孕妇及其新生儿血清总胆酸水平变化对胎儿心脏功能的影响

目的 探讨妊娠肝内胆汁淤积症(ICP)孕妇及其新生儿脐动脉血(脐血)血清总胆酸(TBA)水平变化对胎儿心脏功能的影响.方法 应用循环酶法测定30例ICP孕妇(ICP组)及30例正常妊娠妇女(对照组)外周静脉血及其新生儿脐血TBA水平,单克隆夹心酶联免疫法测定新生儿脐血心肌肌钙蛋白I(cTnI)水平,用彩色多普勒超声诊断仪测定胎儿左心室Tei指数.结果 (1)TBA:ICP组孕妇血清TBA水平为(36.0±9.6)μmol/L,新生儿脐血TBA水平为(10.1±2.0)μmol/L;分别高于对照组的(3.8±0.9)、(5.5±0.4)μmol/L,差异均有统计学意义(P<0.01),且ICP组孕妇血清TBA水平明显高于其分娩的新生儿脐血TBA水平,两者比较,差异有统计学意义(P<0.01),对照组孕妇血清TBA水平明显低于其分娩的新生儿脐血TBA水平,两者比较,差异也有统计学意义(P<0.01).(2)Tei指数:ICP组胎儿左心室Tei指数为0.58±0.04,明显高于对照组的0.43±0.03,差异有统计学意义(P<0.01).(3)cTnI:ICP组新生儿脐血cTnI水平为(0.92±0.23)μg/L,明显高于对照组的(0.52±0.10)μg/L,差异也有统计学意义(P<0.01).(4)ICP组脐血TBA水平与孕妇血清TBA、脐血cTnI水平及胎儿左心室Tei指数均呈正相关关系(r=0.769、0.635、0.758,P<0.01);脐血cTnI水平与胎儿左心室Tei指数呈正相关关系(r=0.637,P<0.01).结论ICP胎儿存在左心室功能异常及心肌损伤,这种损伤可能与孕妇血TBA水平升高有密切关系;胎儿左心室Tei指数可作为监测ICP胎儿心脏功能及心肌损伤程度的指标.     

肝内胆汁淤积症孕妇血胆汁酸预测围生儿预后最佳临界值的探讨

目的 :探讨肝内胆汁淤积症 (ICP)孕妇血清胆汁酸水平在预测围生儿预后中的最佳临界值。方法 :通过受试者工作特征曲线寻找和确定用于预测围生儿预后不良的最佳临界值 ,并以此临界值为界分组分析 2 0 8例ICP孕妇血清胆汁酸值与围生儿的预后。结果 :预测发生围生儿预后不良的胆汁酸最佳临界值为 30 .75 μmol/L。血清胆汁酸≥ 30 .75 μmol/L组围产儿死亡率、胎儿宫内窘迫、早产、新生儿窒息的发生率比 <30 .75 μmol/L组高 ,差异有显著性 (P <0 .0 5 ) ,但出生缺陷发生率两组差异无显著性 (P >0 .0 5 )。结论 :血清胆汁酸水平是预测ICP孕妇围生儿预后的一项重要指标 ,其预测围生儿预后的最佳临界值为30 .75 μmol/L ,灵敏度为 82 % ,特异度为 72 .2 %。当血总胆汁酸水平≥ 30 .75 μmol/L时围生儿预后不良发生率明显增加     

妊娠期肝内胆汁淤积症胎儿胆汁酸水平与肺表面活性物质的相关性研究

目的 探讨妊娠期肝内胆汁淤积症(ICP)胎儿总胆汁酸水平与胎儿肺表面活性物质(PS)的关系.方法 选择2008年4月至2010年2月在中南大学湘雅二医院住院行剖宫产分娩的ICP孕妇55例(ICP组),记录ICP组孕妇的新生儿出生至产后7 d的一般情况,凡符合胎儿窘迫、新生儿窒息、新生儿呼吸窘迫综合征其中1项者为病理围产儿,无上述情况为正常围产儿.另选同期健康孕妇23例为对照组.采用循环酶法测定两组孕妇血、脐血及羊水中总胆汁酸水平;ELISA法测定两组胎儿脐血肺表面活性蛋白A(SP-A)水平;高效液相色谱法测定两组羊水中磷脂酰胆碱(PC)、磷脂酰肌醇(PI)、溶血卵磷脂(LPC)、神经鞘磷脂(SM)的含量.结果 (1)ICP组孕妇血、脐血及羊水中总胆汁酸水平分别为(30.1±7.9)、(9.3±3.3)及(4.4 ±1.5)mmol/L,明显高于对照组的(4.8±2.2)、(4.9±0.9)及(1.4±1.1)mmol/L,两组分别比较,差异均有统计学意义(P＜0.05).(2)ICP 组胎儿脐血SP-A水平为(29.5±6.4)μg/L,明显高于对照组的(22.6±7.4)μg/L,两组比较,差异均有统计学意义(P＜0.05).(3)ICP组中病理围产儿20例,健康围产儿35例,病理围产儿脐血总胆汁酸及SP-A水平分别为(10.9±2.2)mmol/L及(37.0±5.9)μg/L,健康围产儿分别为(8.0±2.8)mmol/L及(26.7±4.8)μg/L,两者比较,差异有统计学意义(P＜0.05).(4)脐血总胆汁酸水平分别与孕妇血、羊水总胆汁酸水平呈正相关(r1=0.706,r2=0.763,P＜0.05);脐血SP-A水平与脐血总胆汁酸水平呈正相关(r3=0.494,P＜0.05).(5)ICP组羊水中PC及PI的含量分别为(65.4±7.2)及(3.8±0.6)mg/L,均明显低于对照组的(69.7±3.7)及(4.3±0.7)mg/L,两组比较,差异有统计学意义(P＜0.05);ICP组羊水LPC的含量为(4.8±0.9)mg/L,明显高于对照组的(4.2±0.6)mg/L,两组比较,差异有统计学意义(P＜0.05);ICP组羊水SM的含量为(3.5±0.8)mg/L,与对照组的(4.0±0.5)mg/L比较,差异无统计学意义(P＞0.05).(6)ICP组羊水PC/LPC比值(14.2±3.2)明显低于对照组(16.9±2.5),差异有统计学意义(P＜0.05).(7)脐血总胆汁酸水平与羊水PC、PI的含量均呈负相关(r1=-0.561,r2=-0.407,P＜0.05);与LPC含量无相关性(r3=0.260,P＞0.05).结论 ICP孕妇的胎儿脐血及羊水中总胆汁酸水平均明显高于健康孕妇,其胎儿PS的改变与胎儿体内高总胆汁酸水平有关.

Abstract：

Objective To explore the relationship between total bile acid(TBA)concentration and fetal pulmonary surfactant in intrahepatic cholestasis of pregnancy(ICP).Methods Fifry five patients with ICP(ICP group)who received cesarean section from April 2008 to February 2010 in Second Xiangya Hospital,Central South University,were recruited.The general conditions of the neonates within 7 days after birth in ICP group were recorded.Those with fetal distress,neonatal asphyxia,or neonatal respiratory distress syndrome were referred as pathological neonates, others were referred as normal neonates. Over the same period, 23 healthy gravidas were recruited as control group. Enzymatic method was used to detect the TBA concentrations in maternal blood, cord blood and amniotic fluid. ELISA was employed to measure the urfactant protein A (SP-A) concentration in cord blood. High performance liquid chromatography system was used to detect the concentrations of phesphatidylcholine (PC),phosphatidylinositol (PI),lysophosphatidylcholine ( LPC), and sphingomyelin(SM) in amniotic fluid. Results ( 1 ) The concentrations of TBA in maternal blood, cord blood and amniotic fluid were ( 30. 1 ± 7.9 ), (9. 3± 3. 3 ) and (4. 4 ± 1.5 ) mmol/L in ICP group, (4. 8 ± 2. 2), (4. 9 ± 0. 9) and ( 1.4 v 1.1 ) mmol/L in control group, respectively. The differences between the two groups were significant ( P ＜ 0. 05 ). ( 2 ) The SP-A concentration in cord blood in ICP group was ( 29. 5 ± 6. 4 ) μg/L, significantly higher than that in control group, which was ( 22. 6 ± 7. 4 )μg/L ( P＜ 0. 05 ). ( 3 ) There were 20 pathological neonates and 35 normal neonates in ICP group. In pathological neonates, the concentrations of TBA and SP-A in cord blood were (10.9 ± 2.2) mmol/L,(37.0 ± 5.9 ) μg/L, respectively; and were ( 8.0 ± 2. 8 ) mmol/L, ( 26. 7 ± 4. 8 ) μg/L in normal neonates. The differences were significant (P＜ 0. 05 ). (4) There was a positive correlation between TBA concentration in cord blood and in maternal blood ( r1 = 0. 706, P＜0. 05 ). The TBA concentration in cord blood was positively correlated with SP-A concentration as well ( r3 = 0. 494,P ＜ 0. 05 ). (5) The PC and PI concentrations in amniotic fluid were (65.4 ± 7.2) mg/L and ( 3. 8 ± 0. 6 ) mg/L in ICP group, ( 69. 7 ±3.7) mg/L and (4. 3 ± 0. 7 ) mg/L in control group, respectively. The differences were significant (P ＜0. 05 ). The concentration of LPC in amniotic fluid in ICP group was (4. 8 ±0. 9) mg/L, significantly higher than that in control group (P＜0. 05), which was (4. 2 ±0. 6) mg/L. The concentration of SM in amniotic fluid was (3.5±0. 8) mg/L in ICP group, (4. 0 ± 0. 5 ) mg/L in control group, with no significant difference ( P＞0. 05 ). (6) The ratio of PC/LPC in ICP group ( 14. 2± 3. 2 ) was significantly lower than that in control group ( 16. 9 ± 2. 5 ) ( P＜ 0. 05 ). ( 7 ) The TBA concentration in cord blood was negatively correlated with PC and PI concentrations (r1 = -0. 561, r2 = -0. 407, P ＜ 0. 05 ), and had no correlation with LPC concentration (r3 = 0. 260, P＞ 0. 05). Conclusions ( 1 ) The fetal TBA concentrations in both cord blood and amniotic fluid of patients with ICP was higher than those of healthy gravidas, they were also positively correlated with maternal TBA concentration. (2) ICP resulted in the change of fetal pulmonary surfactant and this change was associated with TBA concentrations in both cord blood and amniotic fluid.     

妊娠期肝内胆汁淤积症胎儿胆汁酸水平与肺表面活性物质的相关性研究

Objective To explore the relationship between total bile acid(TBA)concentration and fetal pulmonary surfactant in intrahepatic cholestasis of pregnancy(ICP).Methods Fifry five patients with ICP(ICP group)who received cesarean section from April 2008 to February 2010 in Second Xiangya Hospital,Central South University,were recruited.The general conditions of the neonates within 7 days after birth in ICP group were recorded.Those with fetal distress,neonatal asphyxia,or neonatal respiratory distress syndrome were referred as pathological neonates, others were referred as normal neonates. Over the same period, 23 healthy gravidas were recruited as control group. Enzymatic method was used to detect the TBA concentrations in maternal blood, cord blood and amniotic fluid. ELISA was employed to measure the urfactant protein A (SP-A) concentration in cord blood. High performance liquid chromatography system was used to detect the concentrations of phesphatidylcholine (PC),phosphatidylinositol (PI),lysophosphatidylcholine ( LPC), and sphingomyelin(SM) in amniotic fluid. Results ( 1 ) The concentrations of TBA in maternal blood, cord blood and amniotic fluid were ( 30. 1 ± 7.9 ), (9. 3± 3. 3 ) and (4. 4 ± 1.5 ) mmol/L in ICP group, (4. 8 ± 2. 2), (4. 9 ± 0. 9) and ( 1.4 v 1.1 ) mmol/L in control group, respectively. The differences between the two groups were significant ( P ＜ 0. 05 ). ( 2 ) The SP-A concentration in cord blood in ICP group was ( 29. 5 ± 6. 4 ) μg/L, significantly higher than that in control group, which was ( 22. 6 ± 7. 4 )μg/L ( P＜ 0. 05 ). ( 3 ) There were 20 pathological neonates and 35 normal neonates in ICP group. In pathological neonates, the concentrations of TBA and SP-A in cord blood were (10.9 ± 2.2) mmol/L,(37.0 ± 5.9 ) μg/L, respectively; and were ( 8.0 ± 2. 8 ) mmol/L, ( 26. 7 ± 4. 8 ) μg/L in normal neonates. The differences were significant (P＜ 0. 05 ). (4) There was a positive correlation between TBA concentration in cord blood and in maternal blood ( r1 = 0. 706, P＜0. 05 ). The TBA concentration in cord blood was positively correlated with SP-A concentration as well ( r3 = 0. 494,P ＜ 0. 05 ). (5) The PC and PI concentrations in amniotic fluid were (65.4 ± 7.2) mg/L and ( 3. 8 ± 0. 6 ) mg/L in ICP group, ( 69. 7 ±3.7) mg/L and (4. 3 ± 0. 7 ) mg/L in control group, respectively. The differences were significant (P ＜0. 05 ). The concentration of LPC in amniotic fluid in ICP group was (4. 8 ±0. 9) mg/L, significantly higher than that in control group (P＜0. 05), which was (4. 2 ±0. 6) mg/L. The concentration of SM in amniotic fluid was (3.5±0. 8) mg/L in ICP group, (4. 0 ± 0. 5 ) mg/L in control group, with no significant difference ( P＞0. 05 ). (6) The ratio of PC/LPC in ICP group ( 14. 2± 3. 2 ) was significantly lower than that in control group ( 16. 9 ± 2. 5 ) ( P＜ 0. 05 ). ( 7 ) The TBA concentration in cord blood was negatively correlated with PC and PI concentrations (r1 = -0. 561, r2 = -0. 407, P ＜ 0. 05 ), and had no correlation with LPC concentration (r3 = 0. 260, P＞ 0. 05). Conclusions ( 1 ) The fetal TBA concentrations in both cord blood and amniotic fluid of patients with ICP was higher than those of healthy gravidas, they were also positively correlated with maternal TBA concentration. (2) ICP resulted in the change of fetal pulmonary surfactant and this change was associated with TBA concentrations in both cord blood and amniotic fluid.     

妊娠期肝内胆汁淤积症胎儿胆汁酸水平与肺表面活性物质的相关性研究

Objective To explore the relationship between total bile acid(TBA)concentration and fetal pulmonary surfactant in intrahepatic cholestasis of pregnancy(ICP).Methods Fifry five patients with ICP(ICP group)who received cesarean section from April 2008 to February 2010 in Second Xiangya Hospital,Central South University,were recruited.The general conditions of the neonates within 7 days after birth in ICP group were recorded.Those with fetal distress,neonatal asphyxia,or neonatal respiratory distress syndrome were referred as pathological neonates, others were referred as normal neonates. Over the same period, 23 healthy gravidas were recruited as control group. Enzymatic method was used to detect the TBA concentrations in maternal blood, cord blood and amniotic fluid. ELISA was employed to measure the urfactant protein A (SP-A) concentration in cord blood. High performance liquid chromatography system was used to detect the concentrations of phesphatidylcholine (PC),phosphatidylinositol (PI),lysophosphatidylcholine ( LPC), and sphingomyelin(SM) in amniotic fluid. Results ( 1 ) The concentrations of TBA in maternal blood, cord blood and amniotic fluid were ( 30. 1 ± 7.9 ), (9. 3± 3. 3 ) and (4. 4 ± 1.5 ) mmol/L in ICP group, (4. 8 ± 2. 2), (4. 9 ± 0. 9) and ( 1.4 v 1.1 ) mmol/L in control group, respectively. The differences between the two groups were significant ( P ＜ 0. 05 ). ( 2 ) The SP-A concentration in cord blood in ICP group was ( 29. 5 ± 6. 4 ) μg/L, significantly higher than that in control group, which was ( 22. 6 ± 7. 4 )μg/L ( P＜ 0. 05 ). ( 3 ) There were 20 pathological neonates and 35 normal neonates in ICP group. In pathological neonates, the concentrations of TBA and SP-A in cord blood were (10.9 ± 2.2) mmol/L,(37.0 ± 5.9 ) μg/L, respectively; and were ( 8.0 ± 2. 8 ) mmol/L, ( 26. 7 ± 4. 8 ) μg/L in normal neonates. The differences were significant (P＜ 0. 05 ). (4) There was a positive correlation between TBA concentration in cord blood and in maternal blood ( r1 = 0. 706, P＜0. 05 ). The TBA concentration in cord blood was positively correlated with SP-A concentration as well ( r3 = 0. 494,P ＜ 0. 05 ). (5) The PC and PI concentrations in amniotic fluid were (65.4 ± 7.2) mg/L and ( 3. 8 ± 0. 6 ) mg/L in ICP group, ( 69. 7 ±3.7) mg/L and (4. 3 ± 0. 7 ) mg/L in control group, respectively. The differences were significant (P ＜0. 05 ). The concentration of LPC in amniotic fluid in ICP group was (4. 8 ±0. 9) mg/L, significantly higher than that in control group (P＜0. 05), which was (4. 2 ±0. 6) mg/L. The concentration of SM in amniotic fluid was (3.5±0. 8) mg/L in ICP group, (4. 0 ± 0. 5 ) mg/L in control group, with no significant difference ( P＞0. 05 ). (6) The ratio of PC/LPC in ICP group ( 14. 2± 3. 2 ) was significantly lower than that in control group ( 16. 9 ± 2. 5 ) ( P＜ 0. 05 ). ( 7 ) The TBA concentration in cord blood was negatively correlated with PC and PI concentrations (r1 = -0. 561, r2 = -0. 407, P ＜ 0. 05 ), and had no correlation with LPC concentration (r3 = 0. 260, P＞ 0. 05). Conclusions ( 1 ) The fetal TBA concentrations in both cord blood and amniotic fluid of patients with ICP was higher than those of healthy gravidas, they were also positively correlated with maternal TBA concentration. (2) ICP resulted in the change of fetal pulmonary surfactant and this change was associated with TBA concentrations in both cord blood and amniotic fluid.     

妊娠肝内胆汁淤积症患者胎儿缺氧的影响因素

目的　探讨妊娠肝内胆汁淤积症 (ICP)患者胎儿缺氧机理及其相关因素。方法　分别测定ICP患者 (30例 ,ICP组 )及正常妊娠妇女 (30例 ,对照组 )新生儿脐动脉血胆汁酸总量 (TBA)、次黄嘌呤 (HX)、内皮素 (ET)及有核红细胞 (NRBC)计数。结果　 (1)ICP组缺氧者 (10例 )脐血HX水平为(18.6 8± 15 .73) μmol/L ,明显高于ICP组无缺氧者 (2 0例 ) [(6 .87± 2 .82 ) μmol/L ]及对照组 [(6 .81±2 .83) μmol/L](P <0 .0 1) ;但NRBC[(4 .2 0± 2 .49)个 / 10 0白细胞 ,(3.40± 2 .2 6 )个 / 10 0白细胞 ,(3.5 0± 1.74)个 / 10 0白细胞 ]及ET水平 [(72 .44± 12 .2 3)ng/L ,(70 .16± 2 6 .6 1)ng/L ,(6 7.2 7± 43.5 6 )ng/L],各组相似 (P >0 .0 5 )。 (2 )ICP组缺氧者脐血TBA为 (2 3.77± 11.82 ) μmol/L ,明显高于ICP组无缺氧者 (14.86± 5 .46 ) μmol/L ,ICP组无缺氧者脐血TBA又高于对照组 [(9.2 8± 4.39) μmol/L](P <0 .0 1) ;且ICP组脐血TBA与HX水平呈正相关 (r=0 .6 89,P <0 .0 1) ;ICP组羊水胎粪污染率明显高于对照组 (5 3.3% ,13.3% ;P <0 .0 1) ,ICP组羊水胎粪污染者脐血TBA[(2 1.44± 9.92 ) μmol/L],明显高于羊水清亮者 [(13.6 9± 5 .74) μmol/L],差异有显著性 (P <0 .0 5 )。 结论　ICP时 ,     

妊娠肝内胆汁淤积症患者高水平胆汁酸对血管内皮细胞生长因子的作用

目的　探讨妊娠肝内胆汁淤积症 (ICP)患者高水平胆汁酸对血管内皮细胞生长因子(VEGF)的作用及其与胎儿窘迫的关系。方法　采用酶联免疫吸附试验 (ELISA)法测定 3 3例ICP产妇(ICP组 )和 3 0例正常晚期妊娠妇女 (对照组 )血清中VEGF水平 ;采用免疫组织化学方法测定两组产妇的胎盘血管密度 ;采用放射免疫法测定两组产妇的血清胆汁酸水平。结果　 (1)ICP组产妇的VEGF水平为 (2 0 72± 17)ng/L ,胆汁酸水平为 (47 9± 14 2 )ng/L ,血管密度为 (68± 5 )个 /高倍镜下 ;对照组产妇VEGF水平为 (2 2 5 6± 3 0 )ng/L ,胆汁酸水平为 (1 6± 0 7)ng/L ,血管密度为 (74± 7)个 /高倍镜下。 (2 )ICP组产妇血清中VEGF水平与胆汁酸水平呈负相关 ,与胎盘血管密度呈正相关。对照组产妇血清中VEGF水平与胆汁酸水平无相关性 ,与胎盘血管密度呈正相关。结论　ICP产妇血清中高水平的胆汁酸对血管内皮细胞具有细胞毒性作用 ,导致内皮细胞分泌VEGF减少 ,造成ICP患者胎盘毛细血管减少 ,母儿间物质交换困难。这可能是ICP患者易发生胎儿窘迫及胎死宫内的原因之一。     

胎盘胆盐输出泵蛋白的表达及其与妊娠期肝内胆汁淤积症的关系

目的：探讨胎盘组织中胆盐输出泵（bile salt export pump,BSEP）的表达水平及其与妊娠期肝内胆汁淤积症（intrahepatic cholestasis of pregnancy,ICP）的关系。方法：选取2012年2月—2013年8月在苏州市立医院本部产科住院分娩的ICP孕妇30例作为研究组（ICP组）,同期分娩的健康妊娠晚期孕妇30例作为对照组,采用免疫组化（SP）法和蛋白质印迹（western blotting）法测定2组孕妇胎盘组织中BSEP蛋白的表达。结果：BSEP蛋白表达于胎盘滋养细胞的细胞质中。ICP患者胎盘组织BSEP的表达低于正常胎盘组织,差异有统计学意义[（0.197 7±0.111 8） vs. （0.616 0±0.384 9）,P＜0.001]。结论：BSEP蛋白在胎盘组织中表达的降低可能与ICP有关。     

妊娠肝内胆汁淤积症患者体液免疫功能的变化及临床意义

目的 :探讨妊娠期肝内胆汁淤积症 (ICP)体液免疫变化的特点及其临床意义。方法 :采用速率散色比浊法和速率法检测 6 0例妊娠晚期ICP患者和 5 0例正常孕妇血清免疫球蛋白、血清补体C3 、C4和胆汁酸水平 ,并观察其与母婴并发症和妊娠结局的关系。结果 :①ICP组IgG水平为 8.2 9± 2 .0 1g/L ,显著低于正常妊娠组 10 .2± 1.97g/L(P <0 .0 5 ) ,IgM水平为 2 .72± 0 .93g/L ,明显高于正常妊娠组 1.6 2± 0 .84g/L(P <0 .0 5 ) ;②ICP患者血清IgG和IgM水平分别与体内胆汁酸浓度 (4 9.99± 36 .1) μmol/L呈负相关和正相关 ,相关系数 (r)分别为 - 0 .5 12和 0 .32 7(P <0 .0 5 ) ;③如将 95 %正常妊娠妇女体液免疫数值作为正常值范围 ,把ICP患者分为体液免疫异常组和正常组 ,则异常组羊水粪染、胎儿宫内窘迫、早产及围生儿死亡率明显增高。结论 :大部分ICP患者的部份体液免疫功能发生了改变 ,其异常程度与围生期母儿结局明显相关 ,可作为监测ICP病情程度的指标     

妊娠肝内胆汁淤积症患者的胎儿淋巴细胞研究

目的探讨胎儿淋巴细胞在妊娠肝内胆汁淤积症(ICP)发病中的作用。方法采用单向混合淋巴细胞反应法,检测20例ICP患者(ICP组)及20例正常孕妇(对照组)的脐血胎儿淋巴细胞与母体外周血已灭活的淋巴细胞、皮肤组织可溶性抗原、蜕膜组织可溶性抗原的增殖反应情况。结果(1)ICP组脐血胎儿淋巴细胞与母体已灭活的淋巴细胞混合反应中,胎儿淋巴细胞的增殖反应程度为2．75±0．36,显著高于对照组的1．45±0．19,两组比较,差异有统计学意义(P＜0．05);(2) ICP组脐血胎儿淋巴细胞与母体蜕膜组织可溶性抗原混合反应中,胎儿淋巴细胞的增殖反应程度为1．45±0．19,显著高于对照组的0．67±0．24,两组比较,差异有统计学意义(P＜0．05);(3)ICP组脐血胎儿淋巴细胞与母体皮肤组织可溶性抗原反应中,胎儿淋巴细胞的增殖反应程度为1．22±0．44,显著高于对照组的0．66±0．27,两组比较,差异有统计学意义(P＜0．05)。结论胎儿淋巴细胞可能是ICP发病过程中的主要效应细胞之一;母-胎间免疫失衡是ICP发病的重要机制之一。     

妊娠肝内胆汁淤积症患者胎盘合体滋养细胞超微结构的观察与脐静脉血总胆酸水平的测定

目的探讨妊娠肝内胆汁淤积症(ICP)患者是否存在胎盘合体滋养细胞超微结构损伤及胎儿胆酸水平的变化。方法选取ICP患者10例(ICP组)和正常孕妇10例(正常组),采用细胞形态学计量方法观察两组孕妇胎盘合体滋养细胞体视学参数变化;采用循环酶法检测两组孕妇分娩胎儿的脐静脉血总胆酸水平。结果(1)ICP组胎盘合体滋养细胞微绒毛的数目及数密度分别为(21±12)个/视野及(1.9±1.3)μm-3,明显少于正常组的(35±11)个/视野及(4.1±3.2)μm-3,两组比较,差异有统计学意义(P<0.05);ICP组胎盘合体滋养细胞微绒毛平均体积及表面积密度分别为(0.1200±0.0050)μm3、(2.500±0.600)μm2/μm3,明显大于正常组的(0.0500±0.0010)μm3及(1.300±0.400)μm2/μm3,两组比较,差异有统计学意义(P<0.05)。(2)ICP组胎盘合体滋养细胞线粒体的平均体积、表面积密度及体积密度分别为(0.0200±0.0020)μm3、(0.600±0.010)μm2/μm3及(0.0800±0.0090)μm3/μm3,明显大于正常组的(0.0100±0.0050)μm3、(0.500±0.030)μm2/μm3及(0.0500±0.0020)μm3/μm3,两组比较,差异有统计学意义(P<0.05)。(3)ICP组胎盘合体滋养细胞内质网的平均体积、表面积密度及体积密度分别为(0.0200±0.0010)μm3、(0.900±0.010)μm2/μm3及(0.0900±0.0050)μm3/μm3,明显大于正常组的(0.0100±0.0030)μm3、(0.500±0.030)μm2/μm3及(0.0500±0.0010)μm3/μm3,两组比较,差异有统计学意义(P<0.05)。(4)ICP组胎儿脐静脉血总胆酸水平为(8.6±3.2)μmol/L,正常组为(4.6±1.5)μmol/L,两组比较,差异有统计学意义(P<0.05)。结论ICP患者高水平的胆酸可能损伤胎盘合体滋养细胞的细胞器,影响胎盘对胆酸的运输功能。     

妊娠期肝内胆汁淤积症发生死胎的临床因素分析

目的 探讨妊娠期肝内胆汁淤积症(ICP)孕妇发生胎儿死亡的临床特点、实验室指标及胎儿监护手段.方法 对1999年1月至2010年12月浙江大学医学院附属妇产科医院收治的发生死胎的21例ICP孕妇的临床资料进行回顾性分析.结果 (1)21例ICP孕妇的平均年龄(30.2±4.6)岁,其中＞35岁者4例;经产妇6例,1例2年前因ICP发生死胎而引产1次;20例单胎妊娠,1例双胎妊娠.(2)21例ICP孕妇的死胎均发生在孕晚期,胎儿死亡的孕周为29～41周,平均(33.8±4.2)周.12例发生在孕29～37周,9例发生在孕37周后.9例为门诊B超检查时确诊胎死宫内;9例因诊断ICP入院治疗期间发生胎心消失;2例临产后胎心消失;1例胎心监护提示V型减速,拟行急诊刮宫产术于麻醉期间胎心消失.在所有ICP孕妇中围产儿死亡率为0.148%(21/14 184).(3)21例ICP孕妇均有皮肤瘙痒,其中11例有全身皮肤瘙痒.10例在发生死胎前自觉胎动减少或消失.21例ICP孕妇血清甘胆酸水平均升高,其中21.49～64.48 μmol/L 11例,t≥64.48 μmol/L 10例.血清总胆汁酸水平升高16例(另5例未检查),最高达270μmoL/L.血清丙氨酸氨基转移酶和天冬氨酸氨基转移酶水平升高14例,总胆红素＞21μmol/L 7例,直接胆红素升高12例.21例ICP孕妇中,重度15例,轻度6例.(4)9例孕妇门诊即确诊宫内死胎未做胎心监护,其余12例住院检查结果 为:胎心监护结果 可疑2例,无应激试验(NST)提示胎心轻度V型减速1例,B超提示脐动脉舒张期血流缺如3例,胎儿生物物理指标评分低值1例.(5)21例ICP孕妇均经阴道分娩.6例为自然宫缩娩出死胎,其余15例予米非司酮配合依沙吖啶羊膜腔注射或缩宫素引产,14例在48 h内成功娩出死胎,仅1例追加地诺前列酮栓后引产成功.所有死胎外观无异常,脐带长度均在正常范围,有4例脐带绕颈或绕体.胎盘胎膜外观无异常,18例羊水Ⅲ度胎粪污染,2例合并羊水过少.10例行死胎及胎盘病理检查,其中1例合并多发畸形,其余死胎病理检查未见明显异常,10例胎盘病理检查均有绒毛膜周围或底蜕膜、大血管周围的纤维蛋白沉积,同时伴有钙化、退行性变、红色梗死及局灶性合体细胞结节增多.结论 ICP孕妇发生死胎的孕周常在孕晚期,时间常在正常宫缩后,ICP重度可能是发生死胎的关键因素;尚无有效的胎儿监护指标可预测死胎的发生.因此,应综合评估病情,加强胎儿监护,适时终止妊娠.

Abstract：

Objective To investigate the clinical features,critical laboratory parameters,and fetal monitoring methods in intrahepatic cholestasis of pregnancy(ICP).Methods A retrospective analysis of 21 cases of ICP suffered with fetal death in Women's hospital.School of Medicine.Zhejiang University from January 1999 to December 2010 were discussed.Results(1)The average age of ICP patients suffered with fetal death were(30.2±4.6)years old.Among them,4 cases were older than 35 years,six cases were multipara.oneo of them suffered stillbirth 2 year before.Twenty cases were singleton pregnancies and 1 cage was twin pregnancy.(2)All 21 cases of fetal death occurred in the third trimester,12 cases occurred before 37 weeks,9 cases after 37 weeks.Nine cases were diagnosed by ultrasound in outpatient clinics,fetal heart beat disappeared in 9 patients after admission because of ICP, two disappeared after labor, one during anesthesia before emergent surgery. Perinatal mortality rate of ICP was 0. 148% (21/14 184), and fetal death occurred from 29 to 41 weeks with an average gestational age of ( 33.8 ± 4. 2 ) weeks, ( 3 ) Puritus occurred in all 21 cases while 11 of them had pruritus all over the body. Ten pregnant women felt the fetal movement decreased or disappeared before diagnosis of fetal death. The glycocholic acid levels increased in all of the 21 cases. Among them, glycocholic acid levels in 11 cases were (21.49 -64. 48) μmol/L, while in 10 cases were ≥64. 48 μmol/L Serum bile acid levels elevated in 16 cases which had been analyzed ( the other 5 cases had not been checked ), and the highest level reached 270 μmol/L Serum alanine aminotransferase and aspartate aminotransferase were increased in 14 cases. Seven cases had their total bilirubin ＞21 μmoL/L, and 12 cases had their direct bilirubin levels significantly elevated. Among the 21 cases of ICP, 15 cases were in severe status, while the other 6 cases were mild. (4) Nine patients had no antepartum surveillance since fetal death were diagnosed before admission. The results of antepartum surveillance were as follows: 2 cases had nonreassuring nonstress test (NST), one had mild "V" type deceleration. Absence of diastolic flow in umbilical artery were found in 3 cases, and low fetal biophysical score was got in one case. ( 5 ) All 21 patients had vaginal delivery. Six of them delivered after natural contraction, and the remaining 14 cases delivered after oral intake of mifepristone and amniotic injection of ethacridine, or oxytocin induced labor within 48 hours, only one case delivered after additional dinoprostone suppositories. The appearance of fetus, placentas and membranes were normal, the lengths of umbilical cord were average. Four cases were found with cords binding the necks or the bodies. Eighteen cases had grade Ⅲ amniotic fluid with meconium-stained, and 2 cases complicated by oligohydramnios. Ten cases had their fetuses and placentas examined by pathologist. Among them, one case had multiple malformations, no more obvious pathological abnormalities were found in other fetuses. Pathologic examination showed that fibrin deposited around chorion and deciduas basalis, large vessels accompanied by calcification, degeneration,hemorrhagic infarction, and increased focal syncytial nodules could be seen in all of the ten placentas. Conclusions Fetal death in pregnant women with ICP of ten occurs after the contractions, Severe ICP may be a key factor that involved in the occurrence of fetal death. Up to now, there is no valid indicators in fetal monitoring, which can predict fetal death. Extensive assessment of the severity and careful antepartum surveillance should be achieved before timely termination of pregnancy.     

克拉玛依地区妊娠肝内胆汁淤积症流行病学调查结果分析

目的　了解本地区妊娠肝内胆汁淤积症(intrahepatic cholestasis of pregnancy, ICP)的发病率及发病特点。　方法　从妊娠20~24周开始普查,动态观察至36周以上,以总胆汁酸酶循环法测定血清总胆汁酸(total bile acid,TBA),TBA>28.5μmol /L为异常,同时复查肝功能加以确诊。　结果　共普查1275例,确诊为ICP 的患者102 例,发病率为8.00%。妊娠33~36 周ICP的发病率(66/351,18.80%)明显高于其他不同孕龄组(P<0.01)。少数民族孕妇ICP的发病率(47/328,14.33%)高于汉族孕妇(55/947, 5. 81%) (P< 0. 01)。有ICP 高危因素的患者ICP 发病(10/67,14.93%)高于无高危因素组(92/208,7.62%)(P<0.01)。　结论　克拉玛依地区ICP的发病率为8 00%,为ICP的高发地区。少数民族孕妇ICP的发病率明显高于汉族发病率。ICP的发病与孕周、孕妇年龄、家族、服药史等有一定的相关性。TAB在整个孕期的波动范围较大。