抗磷脂综合征的围产期抗凝治疗

抗磷脂综合征(APS)是一组以弥漫性动静脉血栓形成、病理妊娠和持续性抗磷脂抗体阳性为特征的综合征。APS能增加复发性流产、早产、死产、子痫前期、胎儿生长受限等妊娠并发症的发生率。不利的妊娠结局和妊娠期血栓形成之间有关联。围产期APS的治疗主要是对症治疗、防止再次发生血栓和病理妊娠。低剂量阿司匹林和肝素能改善APS的妊娠结局。     

抗磷脂综合征合并妊娠干预时机对妊娠结局的影响分析

目的分析抗磷脂综合征(antiphospholipid syndrome,APS)合并妊娠不同干预时机对产科和围产结局的影响,探讨APS早期干预对于降低产科并发症和改善母儿结局的作用。方法对2006年1月至2014年12月北京大学第三医院收治的127例原发性抗磷脂综合征合并单胎妊娠并分娩的孕妇的临床资料进行回顾性分析,按照围孕期和孕期针对APS不同的干预时机分为未干预组、孕前干预组、孕14周干预组及≥孕14周干预组,分析妊娠期APS干预时机对妊娠结局的影响。结果 APS未干预组早发子痫前期的发生率显著高于其他各时期干预组(P0.008);孕早期干预组早发子痫前期的发生率显著低于孕14周后干预组(P0.008)。APS未干预组和≥孕14周干预组早发子痫前期、胎儿生长受限、羊水过少、新生儿窒息、血栓的发生率均高于孕前干预组和孕14周干预组,早发子痫前期和胎儿生长受限的发病率在APS不同干预时机组中差异有统计学意义(P0.001,P0.05)。孕14周干预与37周之后分娩呈正相关(OR=5.515,95%CI:1.876~16.215,P=0.027)。结论早期排查和干预APS有利于改善APS妊娠者的产科和围产结局。     

应用静脉滴注人免疫球蛋白联合抗凝疗法治疗妊娠早期合并抗磷脂综合征临床分析

目的 探讨静脉滴注（静滴）人免疫球蛋白联合抗凝疗法治疗妊娠早期合并抗磷脂综合征（APS）临床价值。 方法 回顾性分析2013年5月至2014年10月沈阳市妇婴医院350例有不良孕产史的妇女,排除其他常见原因后,进行抗心磷脂抗体(ACA)、抗β2-糖蛋白1（β2-GP1）抗体测定,再结合其不良孕产史,其中79例患者诊断为抗磷脂综合征（APS）,15例APS患者接受单纯口服阿司匹林治疗（Ⅰ组）,26例APS患者接受低分子肝素联合阿司匹林治疗（Ⅱ组）,38例APS患者接受静滴人免疫球蛋白联合低分子肝素、阿司匹林治疗（Ⅲ组）。 结果 Ⅲ组38例APS患者中有34例妊娠至13周末,4例流产,流产率为10.5%;Ⅱ组18例妊娠至13周末,8例流产,流产率为30.8%;Ⅰ组7例妊娠至13周末,8例流产,流产率高达53.3%。结论 应用静滴人免疫球蛋白联合抗凝疗法治疗妊娠早期合并抗磷脂综合征可明显改善孕早期妊娠结局,为治疗妊娠合并APS的有效方法。     

抗磷脂综合征与病理妊娠

抗磷脂综合征(antiphospholipid syndrome，APS)是指抗磷脂抗体(antiphospholipid antibody，APA)阳性并伴有血栓形成或病理妊娠的一组临床征象的总称。妊娠合并抗磷脂综合征的患者也可出现血小板减少的临床表现。     

非标准抗磷脂抗体检测对于风湿病合并不良妊娠患者的治疗意义

抗磷脂综合征(APS)的诊断普遍依据2006年版悉尼标准,非标准抗磷脂综合征(NC-APS)是近年来对于不完全满足悉尼标准但又合并APS相关不良妊娠事件提出的概念.在对这些有不良妊娠结局患者的研究中,开展非标准抗磷脂抗体(NC-aPL)的检测有助于提高NC-APS的诊断率,也使风湿病患者不良妊娠风险评估及治疗能得到更多...     

妊娠合并抗磷脂综合征四例临床分析

妊娠合并抗磷脂综合征(antiphospholipid synalrome, APS)指由抗磷脂抗体引起的一组临床征象的总称,主要表现为血栓形成、习惯性流产、血小板减少等,临床并不多见,由于常引起不良妊娠结局或形成动静脉血栓,对母儿造成严重的危害,需引起妇产科医生的重视.现将我科诊治的4例妊娠合并APS分析如下.     

妊娠合并抗磷脂综合征的诊治

抗磷脂综合征(antiphospholipid syndrome,APS)是指抗磷脂抗体(antiphospholipid antibody,APA)阳性并伴有血栓形成或病理妊娠的一组临床征象的总称,可引起早产、流产、先兆子痫、胎儿生长受限等多种不良妊娠结局。2006年公布的《关于APS分类诊断修订标准的国际共识声明》提出了APS的最新诊断标准。妊娠合并APS的治疗包括单独或联合应用免疫抑制剂和抗凝剂、静脉注射免疫球蛋白、血浆交换等。     

抗磷脂抗体综合征、代谢综合征与早发型重度子痫前期的相关性

近年来在对早发型重度子痫前期特点的研究中发现,血液高凝、慢性DIC、脂质过氧化、血管内皮损伤易形成血栓前状态.同时又发现该种疾病常合并代谢综合征及抗磷脂抗体综合征(APS),而APS、代谢综合征早在早发型重度子痫前期发病前就已存在,并且随着病情的发展而加重.     

自身免疫性疾病子痫前期的防范

子痫前期是常见的妊娠期并发症,孕产妇及围产儿患病率和病死率较高,以妊娠20周后出现高血压和蛋白尿为主要临床表现。在子痫前期出现临床症状之前对子痫前期高危人群进行预测较为困难。系统性红斑狼疮（SLE）和抗磷脂综合征（APS）患者妊娠期子痫前期发生的风险更高。对SLE和APS患者在妊娠期间子痫前期发病机制的理解有助于解释这些自身免疫性疾病患者为什么子痫前期发生率增加。对高危SLE和APS患者的子痫前期进行早期预测和识别,对这些高危患者进行密切监测和治疗,是改善不良母儿结局的关键。对高危SLE和APS患者使用小剂量阿司匹林预防治疗是迄今为止最好的子痫前期的预防方法。     

子痫前期HELLP和APS血清游离脂肪酸水平对滋养细胞脂质沉积影响的研究

目的探讨子痫前期,HELLP综合征和抗磷脂综合征血清中游离脂肪酸水平对滋养细胞内脂质沉积的不同影响。方法采用早发型重度子痫前期（E-PE组）、重度子痫前期并发HELLP（PE-HELLP组）及抗磷脂综合征（APS组）的不同病理妊娠血清和正常妊娠孕妇（NC组）血清孵育体外原代培养人绒毛滋养细胞和细胞系HTR8/SVneo。ELISA法检测血清中CHO、TG和FFA含量;脂肪特殊染色检测细胞内脂滴沉积。结果E-PE组和APS组中血清FFA水平和滋养细胞内脂滴沉积均明显高于PE-HELLP组及NC组（P〈0.05）;PE-HELLP组中血清FFA水平和滋养细胞内脂滴沉积高于NC组（P〈0.05）。血清游离脂肪酸水平与滋养细胞内脂质沉积量呈正相关（R=0.8669、0.8435、0.7734,P〈0.05）。结论早发型重度子痫前期、HELLP和APS间存在不同程度的脂肪酸氧化代谢异常。     

体外受精/卵胞质内单精子显微注射双卵双胎减胎后妊娠结局的病例对照研究

目的探讨双卵双胎妊娠早期减胎为单胎的妊娠结局。方法 2008年1月—2014年12月期间体外受精及卵胞质内单精子注射-胚胎移植(IVF/ICSI-ET)后双胎妊娠早期(孕45~75 d)减胎为单胎者102例(A组),三胎妊娠早期减胎为双胎者73例(B组)以及双胎妊娠未减胎者4 638例(C组),比较其中晚期流产率、早产率等进一步的妊娠结局。结果 IVF/ICSI-ET后A组与B组和C组比较,早产率(10.8%,58.6%,42.1%)、低出生体质量儿率(6.8%,44.1%,30.3%)明显降低,孕周[(38.0±2.0)周,(35.7±2.3)周,(36.4±2.1)周]、出生体质量[(3.17±0.53)kg,(2.51±0.59)kg,(2.69±0.53)kg]明显增加,差异有统计学意义(P0.05),中晚期流产率差异无统计学意义(P0.05)。结论 IVF/ICSI后的双卵双胎妊娠,于孕早期行减胎术安全,具有更好的妊娠结局。     

The reasons for termination of pregnancy in the third trimester.

OBJECTIVE: To analyse the process in making decisions leading to termination of pregnancy in the third trimester and to evaluate the maternal morbidity associated with this procedure. DESIGN: Retrospective study. SETTING: The Maternité Port Royal University Hospital, Paris, France. POPULATION: A consecutive series of 956 terminations of pregnancy performed for fetal anomalies in singleton pregnancies, 305 of which were in the third trimester and 651 in the second. MAIN OUTCOME MEASURES: Indications for termination of pregnancy; process leading to late termination of pregnancy; maternal morbidity. RESULTS: One hundred and thirteen (37%) third trimester terminations of pregnancy were associated with false negative resulted from the results of earlier screening tests. In 15 terminations (5%), the decision was postponed, although the poor fetal prognosis was established earlier. In 55 (18%) the diagnosis was not possible earlier than the third trimester, and in 122 (40%) the diagnosis was possible earlier but the poor prognosis for the fetus was not established until the third trimester. Maternal morbidity due to termination of pregnancy was similar in the second and third trimester. CONCLUSION: One-third of late terminations of pregnancy could have been avoided by more efficient screening in the second trimester. However, because fetal prognosis is not always clear when a malformation is diagnosed, postponing the decision until fetal development allows more thorough evaluation and may avoid unnecessary termination of pregnancy in the second trimester. This could be the main beneficial aspect of not setting a limit to the gestational age for performing termination of pregnancy.     

Pharmacokinetics of low molecular weight heparin and unfractionated heparin in pregnancy

OBJECTIVE: Little pharmacokinetic data are available for either low molecular weight heparins (LMWHs) or unfractionated heparins (UFHs) in pregnancy. The objectives of this study were to determine whether differences exist in the pharmacokinetics of dalteparin and UFH before and during the first, second, and third trimesters of pregnancy in women with the antiphospholipid antibody syndrome (APS). Adjustments in our dosing protocol would be made if differences existed. METHODS: Women with APS who were contemplating pregnancy were randomized to dalteparin 2500 U, 2500 U, 5000 U, and 7500 U daily, or UFH 5000 U, 5000 U, 7500 U, and 10,000 U every 12 hours, prior to pregnancy and the first, second, and third trimesters, respectively. Serial plasma concentrations of heparin were measured during 4 blood sampling days by determining anti-factor Xa activity. RESULTS: Fifteen (n = 9 receiving dalteparin and n = 6 receiving UFH) completed all four sampling periods. For dalteparin, significant differences (P <.05) were detected, using area under the curve (AUC), between pre-pregnancy versus third trimester, first versus second trimester, first versus third trimester, and second versus third trimester. No significant differences were detected in the UFH group. CONCLUSION: In APS, our original dosing protocol of dalteparin yielded significant differences (P <.05) in drug exposure throughout pregnancy. Based on these results, we recommend a prophylactic dalteparin dosing regimen of 2500 U every 24 hours pre-pregnancy (and for 6 weeks postpartum), and 5000 U every 24 hours during the first, second, and third trimesters. Due to lack of significant differences in AUC throughout pregnancy for UFH, we recommend continuing with our original dosing protocol.     

Placental transfer of Zidovudine in first trimester of pregnancy

OBJECTIVE: Zidovudine is one of the most common antiretroviral drugs used to prevent vertical transmission of human immunodeficiency virus. However, it is not recommended for use in the first trimester of pregnancy because of reservations about its potential teratogenicity during the organogenesis phase. The objective of this study was to investigate the placental transfer of zidovudine in the first trimester of human pregnancy. METHODS: Twenty-six pregnant women were given 2 oral doses of zidovudine (200 mg) before first trimester surgical termination of pregnancy. Maternal blood, fetal tissue, and coelomic and amniotic fluid were collected for drug analysis. RESULTS: Zidovudine was detected in all samples of maternal serum and fetal tissue but present in only 7 samples of amniotic and coelomic fluid. Zidovudine concentration in fetal tissue was similar to that of maternal serum. The median fetal/maternal ratio was 0.92 and was not associated with gestational age (r = 0.03, P = .89). CONCLUSION: Zidovudine crossed the first trimester human placenta readily and achieved the level of maternal serum rapidly. Patients who choose to take zidovudine in first trimester of pregnancy should be counseled about the potential fetal effects.     

Antiphospholipid antibodies and pregnancy loss: a disorder of inflammation

The antiphospholipid syndrome (APS) is a leading cause of miscarriage and maternal and fetal morbidity. APS is characterized by thrombosis and pregnancy loss that occur in the presence of antiphospholipid (aPL) antibodies. Using a mouse model of APS induced by passive transfer of human aPL antibodies, we have shown that complement activation plays an essential and causative role in pregnancy loss and fetal growth restriction, and that blocking activation of the complement cascade rescues pregnancies. Conventional treatment for APS patients is sub-anticoagulant doses of heparin throughout pregnancy. Could heparin prevent pregnancy loss by inhibiting complement? In our experimental model of APS, heparin inhibits activation of complement on trophoblasts in vivo and in vitro, and anticoagulation in and of itself is not sufficient to prevent pregnancy complications. These studies underscore the importance of inflammation in fetal injury associated with aPL antibodies and raise the importance of developing and testing targeted complement inhibitory therapy for patients with APS.     

Cervical fetal fibronectin as a predictor of first trimester pregnancy outcome in unexplained recurrent miscarriage

OBJECTIVE: To determine whether cervical fetal fibronectin is a reliable predictor of first trimester pregnancy outcome in patients with unexplained recurrent miscarriage. STUDY DESIGN: A prospective observational study was carried out on 49 pregnant women with a history of unexplained recurrent miscarriage. In all participants the presence of fetal fibronectin in the cervical secretion was determined with a qualitative rapid immunoassay. The outcome of the first trimester pregnancy was recorded a successful outcome was a pregnancy that progressed beyond 12 weeks of gestation; a miscarriage referred to a pregnancy loss in the first 12 weeks. RESULTS: Of the 49 subjects screened, fetal fibronectin was positive in 17 and negative in 32. Overall, 14 pregnancies resulted in fetal loss before the 12th week of gestation. Fetal cervical fibronectin was positive in 6 of the 14 patients who miscarried and in 11 of the 35 in whom outcome was successful. As predictor of first trimester pregnancy outcome the test had a sensitivity and a specificity of 43% and 69% and positive and negative predictive values of 35%, and 75%, respectively. Subgroup analysis by number of previous miscarriages and maternal age gave similar values. CONCLUSION: This study examines the possible value of cervical fetal fibronectin in predicting first trimester pregnancy outcome. We conclude that the occurrence of positive or negative fetal cervical fibronectin test has only limited predictive value and therefore its use cannot be considered for clinical application.     

妊娠早期子宫动脉的多普勒监测对子痫前期的预测价值

提前识别孕妇患子痫前期的风险,可以降低孕产妇和胎儿的发病率和死亡率。子宫动脉多普勒频谱分析在妊娠中期预测子痫前期的研究已较广泛。利用妊娠早期子宫动脉多普勒来预测子痫前期成为了近年的研究热点。子宫动脉多普勒参数作为单独的标志物,其敏感度不高。妊娠早期子宫动脉多普勒参数(如搏动指数)与母体特征及相关生化标志物(如妊娠相关血浆蛋白A、胎盘生长因子)相结合,对早发型子痫前期的检测率高于90%。但结合生化标志物增加了成本,未来研究的方向是筛选最佳组合的预测模型来早期预测子痫前期。     

Sonographic assessment of the extra-abdominal fetal small bowel in gastroschisis: a retrospective longitudinal study in relation to prenatal complications

OBJECTIVE: An explorative retrospective study following a case-series of fetuses with isolated gastroschisis, to evaluate if small-bowel dilatation may be indicative for emerging obstetric complications. The secondary aim was to establish preliminary normative curves for the external diameter and wall thickness of eventerated fetal small bowel in gastroschisis during the second and third trimester of pregnancy. METHODS AND MATERIALS: Fourteen fetuses with isolated gastroschisis were followed at a single center. Repeated ultrasound examinations for fetal surveillance with measurement of fetal small-bowel diameter and wall thickness over the course of pregnancy until delivery were performed. RESULTS: Longitudinal data analysis showed significantly increasing bowel diameter and wall thickness of eventerated small bowel with advancing gestation. Dilatation of small bowel more than 25 mm in the third trimester of pregnancy was associated with an increased risk of short-term prenatal complications as fetal distress or intrauterine fetal death (PPV 100%; 95% CI: 29.2-100%, NPV 100%; 95% CI: 71.5-100%). CONCLUSIONS: Dilatation of the extra-abdominal fetal small bowel in the third trimester may allow identifying fetuses with increased risk of fetal distress requiring closer monitoring of fetal well-being or delivery in a short interval to prevent impending fetal death.     

应用表观遗传学方法检测母体循环中游离胎儿DNA

目的:探讨表观遗传学方法检测孕妇血浆中游离胎儿DNA水平的应用价值。方法:随机选择早、中、晚期妊娠孕妇各20例,以非妊娠妇女20例为对照组。提取血浆中的总游离DNA,用甲基化特异性PCR(MSP)方法检测各组血浆标本中目的基因m-maspin(一种肿瘤抑制基因启动子的甲基化序列)、u-maspin(前者的未甲基化序列)的表达水平,再进行相对定量,对妊娠组和对照组样本均数进行统计学分析。结果:(1)m-maspin在妊娠早、中、晚期孕妇血浆中的浓度分别是非妊娠妇女血浆中浓度的1.0、1.1、1.1倍,差异无统计学意义(P>0.05);(2)u-maspin在正常非妊娠妇女血浆中未能检测到,在60例孕妇血浆中57例可检测到,它在孕妇血浆中的浓度随妊娠进展呈升高趋势,中、晚期妊娠妇女血浆中其浓度相对于早期妊娠分别为1.7倍和3.1倍,差异有统计学意义(P<0.01)。结论:m-maspin不是妊娠特异性标志物,u-maspin为妊娠特异性标志物。u-maspin基因可作为孕妇血浆中游离胎儿DNA水平变化的表观遗传学标志,相对于以胎儿性别基因作为遗传学标志的检测方法,它有助于扩大非创伤性产前诊断的临床应用范围。