产科抗磷脂综合征的诊断和治疗

产科抗磷脂综合征可导致早期复发性流产、死胎、胎盘功能不全和子痫前期等。小剂量阿司匹林和低分子量肝素为一线治疗方案，但仍有30%的病例治疗失败。难治性产科抗磷脂综合征、灾难性抗磷脂综合征的治疗可以使用羟基氯喹、糖皮质激素、静脉免疫球蛋白和血浆置换。抗磷脂综合征妊娠已成为产科研究的一个重要领域，新的治疗方法不断出现。     

妊娠合并抗磷脂综合征的诊治

抗磷脂综合征（antiphospholipid syndrome,APS）是一种由抗磷脂抗体引起的非炎症性自身免疫病。妊娠合并APS易发生早期反复自然流产,孕晚期胎死宫内,胎儿生长受限,血小板减少,子痫前期或子痫以及胎盘功能障碍等不良妊娠结局,严重危及母儿健康。临床上应充分重视妊娠合并APS的诊断和治疗。     

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。     

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     

子痫前期胎盘因素在胎儿生长受限中的作用

胎儿生长受限(FGR)为子痫前期最常见的并发症,子痫前期和胎儿生长受限的发病基础有共同之处,与胎盘浅着床代偿性分泌一系列异常活性因子有关,并引发胎盘功能不良、胎儿生长受限等妊娠不良结局。近年许多实验着力于进一步研究子痫前期血管生长因子、胎盘内分泌激素及细胞因子的表达差异与FGR发生的相关性,为子痫前期的病情发展及预测妊娠结局和治疗提供新的依据。     

脂联素在子痫前期患者胎盘组织中的表达与其发病的关系

目的 探讨脂联素在子痫前期患者胎盘组织中的表达与其发病的关系.方法 采用免疫组化链霉菌抗生物蛋白-过氧化物连接(SP)法及RT-PCR技术,检测20例正常足月妊娠孕妇(正常妊娠组)、12例轻度子痫前期(轻度子痫前期组)及22例重度子痫前期(重度子痫前期组)患者胎盘组织中脂联素蛋白及其mRNA的表达,并分析其与子痫前期发病的关系.结果 (1)3组孕妇胎盘绒毛合体滋养细胞及细胞滋养细胞胞质内脂联素蛋白均呈阳性表达,且各组内胎盘母面及子面脂联素蛋白的表达水平相互比较,差异均无统计学意义(P＞0.05).(2)重度子痫前期组胎盘组织中脂联素蛋白的表达水平(30 984±14 604)低于轻度子痫前期组(58 360±8910)及正常妊娠组(53 246±17 554),差异均有统计学意义(P＜0.01).重度子痫前期组中妊娠足月者胎盘组织中脂联素蛋白的表达水平(38 890±20 386)与未足月者(29 319±8997)比较,差异无统计学意义(P＞0.05);但与正常妊娠组比较,差异有统计学意义(P＜0.05).(3)3组孕妇胎盘组织中均有脂联素mRNA的表达.其中重度子痫前期组胎盘组织中脂联素mRNA表达水平(1.0±0.2)低于轻度子痫前期组(2.9±0.8)及正常妊娠组(3.3±1.1),差异有统计学意义(P＜0.05).结论 重度子痫前期患者胎盘组织中脂联素mRNA表达水平下降导致其蛋白表达水平也下降,提示脂联素的异常表达参与了子痫前期的发病.     

miRNA在子痫前期发病与诊断中的意义

与正常妊娠的胎盘相比,子痫前期患者胎盘组织中存在着多种差异化表达的miRNA,其中miR-210、miR-455和miR-17-92通过对多种信号途径的调节,影响了胎盘滋养细胞的正常功能,参与了子痫前期的发生。miRNA的独有特性,使其成为新型的生物标记分子,多个研究组探讨了循环miRNA对子痫前期发病的早期诊断或预测能力,初步证实miRNA可以作为子痫前期的早期预测标记物。     

子痫前期发病机制研究进展

子痫前期是一种妊娠期特有疾病,滋养细胞对子宫螺旋动脉重塑障碍可能是子痫前期发病的根本原因,滋养细胞本身异常,以及滋养细胞与其所处微环境相互作用异常都可以导致滋养细胞重塑功能障碍;子痫前期临床表现是功能异常的胎盘释放到母体循环中的一些因子所引起,血管内皮生长因子1可溶性受体是最重要的子痫前期因子之一,有可能成为子痫前期早期诊断新指标.     

转甲状腺素蛋白与子痫前期发病关系的研究

目的通过建立子痫前期孕鼠模型探讨转甲状腺素蛋白与子痫前期发病的关系。方法将健康SPF级CD-1小鼠按雌雄比2:1合笼,雌鼠受孕后,随机将孕鼠分为四组,以使用生理盐水作为对照组,使用亚硝基左旋精氨酸甲酯(L-NAME)建立子痫前期孕鼠模型,另两组使用TTR稳定剂及在子痫前期孕鼠模型上使用TTR稳定剂;观察四组孕鼠的血压情况;使用ELISA方法检测四组孕鼠在妊娠第18天时的尿蛋白情况和不同妊娠天数时血清TTR水平;比较四组孕鼠胎鼠和胎盘重量的差异;用Western blot方法检测四组孕鼠胎盘TTR的蛋白表达水平。结果 (1)模型组孕鼠出现血压升高、尿蛋白明显增加和血清TTR水平下降,与对照组相比差异有统计学意义;给予TTR稳定剂治疗的子痫前期孕鼠出现血压和尿蛋白下降以及血清TTR水平下降缓慢,与模型组相比差异有统计学意义;(2)模型组胎鼠体重明显低于正常对照组,差异具有统计学意义;使用TTR稳定剂治疗的子痫前期孕鼠中,胎鼠体重增加,与模型组相比差异有统计学意义。四组孕鼠胎盘重量和胎盘TTR蛋白表达没有差异。结论血清TTR水平的增加可以改善子痫前期孕鼠的相关症状,包括高血压、蛋白尿和子代的体重,验证了TTR与子痫前期发病的相关性,TTR下降可以导致子痫前期发生。     

RhoA在子痫前期患者胎盘中的表达

目的:检测正常晚期妊娠和子痫前期患者胎盘RhoA的表达,探讨RhoA在子痫前期发病中的作用。方法:用免疫组织化学SP法及RT-PCR检测40例子痫前期和20例正常晚期妊娠胎盘RhoA蛋白及其mRNA的表达。结果:RhoA主要在滋养细胞表达。轻度子痫前期组和重度子痫前期组RhoA蛋白及mRNA均高于正常晚期妊娠组,差异有统计学意义(P<0.05)。结论:子痫前期患者胎盘RhoA的高表达可能与子痫前期的发病有一定的关系。     

Uterine NK cells and macrophages in pregnancy

The presence of immune cells in the placental bed is important for both mother and child. Although various immune cells can be found in the placental bed, such as regulatory T cells and dendritic cells, uterine NK cells and macrophages are the most prominent immune cells in the placental bed in early pregnancy. uNK cell and macrophage numbers in the placental bed decrease in the third trimester. These cells seem to be specifically adapted for their function and environment. uNK cells do not show cytotoxic activity, but are producers of cytokines, growth factors and many other factors. uNK cell function is regulated by inhibitory and activating receptors binding to HLA class I on trophoblast cells. uNK cells are also involved in regulating trophoblast invasion. Macrophages mainly show an M2-like phenotype and also produce cytokines and various other factors. They are important in phagocytosis of various cells and cell debris in the placental bed. Both cell types are also involved in angiogenesis and spiral artery remodeling in the placental bed. In this review we will elaborate on the most important functions of uNK cells and macrophages in the placental bed in humans. We will also discuss animal models, since they may provide clues for function of uNK cells and macrophages in humans.     

Diminished expression of placental isoferritin p43 component in first trimester abnormal pregnancies

Human placental isoferritin (PLF) is a sub-type of human ferritin mainly composed of a 43 kD protein, which has an immunosuppressive activity and may be involved in the downregulation of the maternal immune system during pregnancy. The aim of this study was to evaluate the distribution of p43 in the placental tissue of abnormal first trimester pregnancies. Samples of villous and decidual tissues were collected between 7 and 12 weeks' gestation from 28 missed abortions and eight complete moles. Samples of placental tissue from 20 normal pregnancies of similar gestational age were used as controls. The localization of p43 was determined by immunohistochemical techniques using CM-H9 monoclonal antibody. Compared to controls, specific p43 immunoreactivity was low in the villous syncytiotrophoblast of missed abortions and absent from all villous cellular types in complete moles. These findings correlate well with the low level of maternal serum PLF found previously in early pregnancy failures and molar gestation. This suggests that PLF may be involved in the pathogenesis of early pregnancy disorders related to an abnormal placentation.     

Human Early Placental Development: Potential Roles of the Endometrial Glands

There is strong evidence that the endometrial glands play a key role in regulating placental development in many domestic species, but their contribution in the human has largely been ignored once implantation is complete. Here we re-evaluate their role during the first trimester. Connections between the glands and the intervillous space have been observed from day 17 post-conception through to the end of the first trimester. In the absence of a maternal arterial supply to the early placenta it is believed that the carbohydrate- and lipid-rich secretions represent an important source of nutrients during the first trimester, and possibly the beginning of the second trimester. The secretions also contain a variety of growth factors that may regulate placental morphogenesis since their receptors are present on villous and extravillous trophoblast, and villous endothelial cells. Other components of the secretions may modulate immune responses and trophoblast invasion at the materno-fetal interface. We speculate that lactogenic hormones secreted by decidual cells and the syncytiotrophoblast may act in concert with human chorionic gonadotropin to stimulate the secretory activity of glandular epithelial cells during the first trimester. There is circumstantial evidence, but as yet no conclusive proof, that deficient glandular activity is associated with pregnancy failure in the human.     

Relatively reduced values of plasma alpha-fetoprotein at early second trimester of pregnancies with hypertensive disorders.

Hypertensive disorders during pregnancy implicate placental pathologic conditions, which may interfere with the normal passage of alpha-fetoprotein (AFP) to the maternal blood. We compared the levels of maternal serum (MS) in early second trimester of pregnancies complicated by hypertensive disorders with those of matched controls. The distribution in the study group of MS-AFP multiple of median values was significantly different from the distribution in the control group. Moreover, up to multiple of the median 1.00, the number of hypertensive patients was larger than the number of normotensive pregnant women. The mean level of multiples of the median in the study group was significantly lower than that of the control group (p value = 0.003, 95% confidence interval: -0.30, -0.05). In the analysis of the distinct types of hypertension, the difference remained significant for 85 women in the moderate hypertension subgroup (p value = 0.032, confidence interval: -0.34, -0.02) and was not significant for the severe hypertension subgroup of 22 women (p value = 0.24, 95% confidence interval: -0.57, 0.15) and chronic hypertension subgroup of women (p value = 0.52, 95% confidence interval: -0.44, 0.00). The trend was consistent in all the subgroups. Relatively low values of maternal serum AFP at early second trimester of pregnancies with hypertensive disorders may be a result of placental pathologic involvement and can help in the identification of the women at risk.     

重型胎盘早剥的诊断和处理

胎盘早剥病因未明,是妊娠晚期严重并发症,起病急,发展快,甚至危及母儿生命。尽早发现胎盘早剥能够避免母儿不良结局,如果发生重型胎盘早剥,及时的诊断及处理能够改善母儿预后。     

How to perform transabdominal chorionic villus sampling: a practical guideline

The spread of both first trimester screening for chromosomal abnormalities and the possibility to check for single gene disorders at DNA-analysis has increased the request for chorionic villus sampling (CVS) in the first trimester. In order to perform placental biopsy, two routes are possible: the transcervical (TC) and the transabdominal (TA). In early days, the trancervical technique was the most diffused, but since its introduction into clinical practice, the TA technique has become the approach of choice in detriment of the TC technique. In our institution, we have a 30-year experience in TA-CVS with more than 26?000 procedures performed. Considering the expertise and the volume of procedures undertaken at our unit, we suggest a practical guideline for novel operators in TA-CVS.     

Three-dimensional ultrasound measurement of the placental volume in early pregnancy: method and correlation with biochemical placenta parameters.

Placental size has been an interesting topic of research for many years. The main aim of this study was to investigate the feasibility of measuring the placental volume at the end of the first trimester using three-dimensional (3D) ultrasound and to correlate these volumes to known placental functional indices and to factors affecting the placenta. Women with singleton pregnancies at the end of the first trimester were included into this study. The volume data of the placentae were correlated to the crown-rump length (CRL), placenta-associated plasma protein A (PAPP-A), free beta-human chroangiogonadotropin (f-beta-hCG) and other factors that may affect the placental size or function. A total of 1462 pregnancies could be evaluated. Comparison between CRL and placental volume proved a significant correlation (r=0.43, P< 0.001). Due to the observed proportional growth of CRL and placental volume, a quotient (placental volume/CRL) was calculated for each case. There were no differences between placenta/CRL-quotients in relation to gravidity, parity or smoking. Correlations could be established between the placental volume and PAPP-A and f-beta-hCG (PAPP-A: r=0.28, P< 0.001, f-beta-hCG: r=0.10, P< 0.001). The measurement of the placenta in the first trimester can be performed in a high percentage of cases. The placenta/CRL quotient represents a simple method to compare placentae from different gestational days. The correlation between placental volume and maternal serum screening parameters might provide a chance to refine first trimester Down's syndrome serum screening. Future studies will be needed to evaluate the possible clinical use of first trimester placental volume measurements.     

Macrosomia has its roots in early placental development

Introduction

We sought to determine if early placental size, as measured by 3-dimensional ultrasonography, is associated with an increased risk of delivering a macrosomic or large-for-gestational age (LGA) infant.

Methods

We prospectively collected 3-dimensional ultrasound volume sets of singleton pregnancies at 11–14 weeks and 18–24 weeks. Birth weights were collected from the medical records. After delivery, the ultrasound volume set were used to measure the placental volume (PV) and placental quotient (PQ = PV/gestational age), as well as the mean placental and chorionic diameters (MPD and MCD, respectively). Placental measures were analyzed as predictors of macrosomia (birth weight ≥4000 g) and LGA (birth weight ≥90th percentile).

Results

The 578 pregnancies with first trimester volumes included 44 (7.6%) macrosomic and 43 (7.4%) LGA infants. 373 subjects also had second trimester volumes available. A higher PV and PQ were both significantly associated with macrosomia and LGA in both the first and second trimesters. Second trimester MPD was significantly associated with both outcomes as well, while second trimester MCD was only associated with LGA. The above associations remained significant after adjusting for maternal demographic variables such as race, ethnicity, age and diabetes. Adjusted models yielded moderate prediction of macrosomia and LGA (AUC: 0.71–0.77).

Conclusions

Sonographic measurement of the early placenta can identify pregnancies at greater risk of macrosomia and LGA. Macrosomia and LGA are already determined in part by early placental growth and development.     

The determination of basic fibroblast growth factor (bFGF) in human placental tissue and the changes in bFGF during pregnancy]

The purpose of this study is to develop an assay system for quantification of bFGF in human tissue and to investigate the changes in bFGF content in the human placenta during pregnancy. Sixty-two placental tissue samples from various stages of normal pregnancies were collected. Approximately 28 micrograms bFGF was obtained per 1 kg of placental tissue. The recovery rates were 17.1 +/- 7.4%. The purified samples were confirmed as bFGF by SDS-PAGE and enzyme-linked immunoelectrotransfer blot (EITB) with anti-human bFGF monoclonal antibody. The bFGF readings in the human placenta determined by RIA were 11.81 +/- 2.11 fmol/mg protein (first trimester), 20.45 +/- 4.85 (early second trimester), 9.52 +/- 5.02 (late second trimester), 7.41 +/- 2.07 (third trimester), and 7.75 +/- 1.86 (post trimester). The placental bFGF were significantly high in the early stage of second trimester and declined gradually during the remainder of the pregnancy. The RIA values were correlated closely with the values obtained by bioassay. These results demonstrate that our assay system provides a tool for the quantification of bFGF in biological samples and suggest that bFGF, the active mitogen and angiogenic factor, participates in the formation of the human placenta.     

Comparison of placental three-dimensional power Doppler indices and volume in the first and the second trimesters of pregnancy complicated by gestational diabetes mellitus

Objective: To compare the changes of placental three-dimensional power Doppler indices and volume in the first and the second trimesters of pregnancy with gestational diabetes mellitus (GDM).

Methods: This was a prospective case-control study of singleton pregnancies with risk factors for GDM. Data on placental vascular indices including vascularization index (VI), flow index (FI), and vascularization flow index (VFI), as well as placental volume were obtained and analyzed during the first and the second trimesters between pregnant women with and without GDM.

Results: Of the 155 pregnant women enrolled, 31 developed GDM and 124 did not. VI and VFI were significantly lower in the GDM group during the first and second trimesters (VI: p?=?.023, and VFI: p?=?.014 in the first trimester; VI: p?=?.049, and VFI: p?=?.031 in the second trimester). However, the placental volume was similar in both the groups during the first trimester, while it was significantly increased in the GDM group during the second trimester (p?=?.022). There were no significant differences in FI and uterine artery pulsatility index between the two groups. After adjustments in multivariate logistic regression analysis, significant differences were observed in the first trimester VFI (adjusted odds ratio (OR) 0.76, 95% confidence interval (CI) 0.61–0.93), second trimester VFI (adjusted or 0.83, 95%CI 0.71–0.96), and second trimester placental volume (adjusted or 1.03, 95%CI 1.01–1.05).

Conclusions: Placental vascular indices can provide an insight into placental vascularization in GDM during early pregnancy. VFI rather than placental volume may be a sensitive sonographic marker in the first trimester of GDM placentas.