孕晚期母血清生化指标异常和不良妊娠结局关系的临床研究

随着围生期保健的加强,早期筛查高危妊娠,及时处理,对减少不良妊娠结局有重要意义。最近有报道孕中期母血清生化指标异常与一些不良妊娠结局间存在一定关系。本研究在孕晚期测定HCG、uE3、HPL三个血清生化指标,探讨孕晚期血清生化指标异常是否与不良妊娠结局存在一定的关系。     

孕中期血绒毛膜促性腺激素水平异常改变与不良妊娠结局的关系

目的 探讨孕中期血绒毛促性腺激素（hCG)水平异常改变与先兆子痫、胎膜早破及早产的关系。方法 采用放射免疫技术测定200例孕15－22周妇女血清hCG水平，动态观察其妊娠结局，分析其血hCG水平与妊娠结局的关系。结果 各孕周血hCG水平中位数（M)差异无显著性（P＞0.05）；发展为先兆子痫、膜早破及早产者血hCG水平显著高于正常妊娠结局者，孕中期血hCG水平≥2M者先兆子痫、胎膜早破及早产的发生率分别为30.9%(25/81)、35.8%(29/81)和14.8%(12/81),显著高于血hCG水平＜2M者（8.4%、6.7%、7.6%，P＜0.01）；以总体孕中期血hCG的中位数的2倍为临界值，预测先兆子痫、胎膜早破及早产的特异性、灵敏性、阳性预测值及阴性预测分别为89.4%,68.7%,40.5%和92.7%,73.6%,33.3%,和95.7%;85.6%,50%,14.2%和94.9%。结论 孕中期血hCG升高是先兆子痫，胎膜早破及早产的危险信号，可作为预测不良妊娠结局的指标。     

孕中期孕妇母血清hCG测定对于妊娠高血压综合征的预测性研究

目的 为明确孕中期血清绒毛膜促性腺激素(hCG)的异常升高是否增加妊高征发生的危险及其能否作为预测妊高征的有效指标。方法 在孕中期(13-27周)对432例单胎妊妇进行血清hCG的测定,并将测得值转换成中位数的倍数(mom),随访妊娠情况至产后,利用群组研究的方法,将hCG异常升高组作为研究组,而低于相应阈值的组作为对照组,探讨hCG的异常升高和妊高征的关系。结果 孕中期血清hCG的异常升高增加了重度妊高征(先兆子痫)发生的危险,而与轻中度妊高征的发生无明显关系。当hCG≥2.0 mom、≥2.5 mom或≥3.0 mom时,发生先兆子痫的危险分别是对照组的7.88倍,31.2倍或34.5倍,95％CI分别为1.55-40.12,2.56-68.03,6.31-188.67;95％CI的下限均大于1;筛查的敏感度均为50％,特异度分别为88.7％,93％,97％。结论孕中期血清hCG的异常升高增加了先兆子痫发生的危险,孕中期hCG的异常升高值可作为预报妊高征及监测病情程度的指标。     

3657例孕中期唐氏筛查及产前诊断的临床价值分析

目的探讨孕中期唐氏筛查对检出胎儿染色体异常和妊娠不良结局的临床价值。方法应用时间分辨荧光免疫法对3657例孕中期(14～20+6周)妇女进行血清标记物AFP和free-β-hCG2项指标双标记检测。筛查结果应用LifeCycle和Elipse软件计算唐氏综合征风险。唐氏筛查风险切割值为1∶270,当切割值≥1∶270时为唐氏高危孕妇。对于高危孕妇,于孕18～22周左右进行羊膜腔穿刺,抽取羊水进行胎儿染色体核型分析。并继续追踪胎儿和孕妇情况。结果在有回访资料的3258例孕妇中,去筛查到高危212例,唐氏筛查阳性率为5.8%(212/3657)。其中68例接受羊水或脐血穿刺产前诊断,占筛查高危孕妇的32.1%(68/212);发现胎儿染色体异常8例,异常检出率11.8%(8/68),其中3例唐氏综合征、2例18-三体综合征、1例Turner’s综合征、1例9号染色体臂间倒位、1例平衡易位。唐氏筛查高风险和低风险组不良妊娠结局分别为6.6%和3.4%,呈显著性差异(p0.05)。结论孕中期产前筛查是预测异常胎儿和不良妊娠结局的有效指标。结合羊水培养或脐血培养等产前诊断技术和方法,对预防先天缺陷儿出生有重要临床应用价值。     

妊娠中期唐氏综合征筛查血清标志物异常与不良妊娠结局

目的 探讨妊娠中期唐氏综合征筛查血清标志物异常与不良妊娠结局的关系.方法 2009年1月1日至2011年1月31日在北京协和医院产科门诊进行妊娠中期三联筛查、在本院分娩并随访到妊娠结局者,共1935例.采用时间分辨荧光免疫分析技术测定妊娠中期(妊娠15～20+6周)孕妇血清甲胎蛋白(alpha fetoprotein,AFP)、游离β-人绒毛膜促性腺激素(β-human chorionic gonadotropin,β-hCG)及游离雌三醇(unconjugated estriol,uE3)水平.分析血清标志物正常者与异常者之间不良妊娠结局发生率的差异.采用t检验和x2检验进行统计学分析. 结果 (1)1935例孕妇中,血清标志物正常者(正常组)1255例；异常者680例,包括单项异常者577例,2项异常者89例以及3项异常者14例.根据血清标志物异常的情况,将577例单项异常者分为AFP升高组17例、AFP降低组114例、p-hCG升高组242例、β-hCG降低组139例及uE3降低组65例.AFP降低组妊娠中期体重及β-hCG降低组的分娩孕龄大于正常组[分别为(61.3±9.1) kg与(59.5±8.3) kg、(272.6±11.8)d与(274.4±10.1)d,t=2.21和1.99,P均＜0.01].(2)正常组不良妊娠结局发生率为42.8％(537/1255),与血清标志物异常者(43.7％,297/680)相比,差异无统计学意义(RR=1.02,P=0.71).与正常组相比,AFP升高组前置胎盘及胎盘形态异常发生率[分别为25.5％(32/1255)与2/17、4.1％ (51/1255)与5/17,RR=4.61和7.24]、AFP降低组妊娠期糖尿病(gestational diabetes mellitus,GDM)发生率[8.1％(101/1255)与14.4％ (16/114),RR=1.74]、β-hCG升高组胎盘胎膜滞留发生率[3.5％(44/1255)与6.2％(15/242),RR=1.77]及 β-hCG降低组子痫前期发生率[1.7％(21/1255)与6.5％(9/139),RR=3.87]均升高,差异均具有统计学意义(P均＜0.05).(3)血清标志物2项异常者共89例.AFP低β-hCG高组小于胎龄儿、羊水过少和胎盘早剥发生率均高于正常组[小于胎龄儿:6.9％(2/29)与1.8％(22/1255),RR=3.94;羊水过少:20.7％(6/29)与6.4％(80/1255),RR=3.24]；AFP低uE3低组羊水过少发生率高于正常组[3/14与6.4％(80/1255),RR=3.36]；p-hCG低uE3低组早产和GDM发生率高于正常组[早产:2/6与4.3％ (54/1255),RR=7.75;GDM:3/6与8.0％(101/1255),RR=6.21];差异均具有统计学意义(P均＜0.05).(4)血清标志物3项异常者共14例,这些孕妇的血清标志物异常与妊娠不良结局的关系没有统计学意义. 结论 唐氏综合征筛查血清标志物异常与不良妊娠结局有较为密切的关系,妊娠期应密切监测.     

子痫前期孕妇孕中期血清sEng、sFlt-1水平与妊娠结局的关系研究

目的探究子痫前期(PE)孕妇孕中期血清可溶性内皮因子(sEng)、可溶性fms样酪氨酸激酶1(sFlt-1)水平与妊娠结局的关系。方法回顾性分析2018年1月至2019年1月在甘肃省天水市第一人民医院妇产科生产的98例PE孕妇(疾病组)和健康孕妇98例(健康组)临床资料,依据疾病组妊娠结局不同分为良好组和不良组,对比疾病组、健康组血清sEng、sFlt-1水平及妊娠结局,并对PE孕妇妊娠结局影响因素进行分析。结果疾病组血清sEng、sFlt-1水平较健康组明显高(P 0.05),疾病组不良妊娠结局总发生率明显高于健康组(P 0.05),不良组孕中期血清甘油三脂、总胆固醇、sEng、sFlt-1水平较良好组明显高(P 0.05),孕中期血清sEng、sFlt-1水平为PE孕妇妊娠结局的高危因素(P 0.05)。结论 PE孕妇孕中期血清s Eng、s Flt-1水平明显增高,孕中期PE孕妇血清sEng、sFlt-1水平增高可增加不良妊娠结局发生风险,积极监测孕中期血清sEng、sFlt-1水平对降低PE孕妇不良妊娠结局风险有积极意义。     

孕中期产前筛查435例高风险孕妇妊娠的结局

2001年9月~2005年5月31日应用母血清生化指标二联法(AFP Freeβ-HCG)对妊娠15~20周的5457例孕妇,开展孕中期唐氏综合征筛查,采用血二联测定值加上孕妇年龄、体重及孕周,由软件计算风险率。对筛查为高危孕妇者建议做羊水细胞培养或脐带血细胞培养,明确诊断胎儿染色体。1资料与方法1.1筛查对象筛查对像均来自本院产科门诊,孕14 1~20 6周,年龄在21~48岁,自愿参加产前筛查者。1.2方法采用孕妇空腹静脉血2ml,分离血清保存于-20℃冰箱,筛查指标为孕妇血清AFP和Freeβ-HCG浓度。测定方法采用时间分辨荧光法(DELFLA),Eu和Sm双标记试剂盒,由…     

15230例孕中期唐氏筛查产前诊断的临床应用

目的:探讨孕中期唐氏筛查对检出胎儿染色体异常的预测价值。方法:2008年1月至2009年10月,采用时间荧光免疫分辨法对我院15230例孕中期(15～20+6周)妇女进行血清标志物甲胎蛋白(AFP)、游离雌三醇(uE3)、绒毛膜促性腺激素(β-HCG)3项指标进行检测,对于筛查结果为高风险的孕妇于孕20～24周行羊膜腔穿刺进行胎儿羊水细胞染色体核型分析,并对唐氏筛查情况进行效果评价。结果:984例孕妇唐氏筛查为高风险,高风险率为6.46%,其中唐氏综合征阳性孕妇736例,18-三体阳性78例,神经管缺陷阳性169例。有773例高风险孕妇接受羊水穿刺,发现胎儿染色体异常29例,异常检出率为3.75%,其中唐氏综合征11例,18-三体1例,69,XXX1例。唐氏筛查的敏感性和特异性分别为92.86%和95.25%。结论:孕中期唐氏筛查是预测异常胎儿和不良妊娠结局的有效手段之一,羊水细胞核型分析在产前诊断中具有重要的实用价值。     

血清高糖基化hCG检测在21-三体综合征产前筛查中的意义探讨

目的初步探讨孕母血清高糖基化hCG(HhCG)用于孕中期产前筛查21-三体的临床意义。方法采用Nichols全自动化学免疫发光分析仪测定115例孕15～20周的孕妇(包括17例21-三体妊娠和98例正常妊娠)的血清高糖基化hCG水平。结果 17例21-三体妊娠的孕妇HhCGMoM值中位数为10.11,约是正常妊娠中位数值(3.55)的3倍。将115例孕妇按AFP、F-β-hCG筛查结果分成21-三体妊娠者和高风险、低风险正常妊娠3组,3组数据呈对数正态分布,组间比较,21-三体妊娠孕妇HhCGMoM值高于高风险、低风险正常妊娠(P0.02、P0.001)。除此,17例21-三体妊娠者HhCGMoM值均大于2.9(文献提示的21三体高风险判断阈值);2例AFP、F-β-hCG产前筛查为假阴性患者其HhCGMoM值分别为7.5、10.11,均大于2.9。结论 21-三体妊娠者孕中期血清HhCG较正常妊娠升高,血清HhCG指标有产前筛查的应用价值。     

孕中期NIPT联合血清AFP、free β-hCG及uE3检测在唐氏综合征筛查的临床价值

目的探究无创产前DNA检测(NIPT)联合血清学指标应用于唐氏综合征孕中期筛查的临床效果。方法对2 590例孕妇临床资料进行回顾性分析,以羊膜穿刺/脐静脉穿刺细胞染色检查结果为"金标准",比较NIPT及联合血清甲胎蛋白(AFP)、游离β-人绒毛促性腺激素(free β-hCG)、非结合雌三醇(uE3)对唐氏综合征的筛查准确度差异,采用受试者工作特征(ROC)曲线,描述各检查方案对唐氏综合征的预测价值。结果 NIPT联合血清学指标筛查唐氏综合征准确度为87.34%(2 262/2 590),显著高于单纯NIPT或单纯血清学指标筛查结果(P0.05),其ROC曲线下面积(AUC)为0.790(95%CI=0.663～0.918)。结论 NIPT联合血清AFP、free β-hCG及uE3能有效增强孕中期唐氏综合征筛查的准确性,对不良妊娠结局有较高预测价值。     

中孕期母体血清游离β-HCG水平过高与不良妊娠结局相关性的研究

目的:探讨中孕期母体血清人绒毛膜促性腺激素游离β亚基(游离β-HCG)水平异常与早产、出生缺陷、死胎等不良妊娠结局的相关性。方法:回顾分析分娩产妇在中孕期测定的血清游离β-HCG水平,按血清游离β-HCG中位数倍数(MOM)分组,统计分析不同组间早产等不良妊娠结局发生率的差异,探讨不良妊娠结局与中孕期母体血清游离β-HCG水平异常的相关性。结果:中孕期母体血清游离β-HCG过高(≥2.0MOM)的产妇组,早产等不良妊娠结局发生率为31.23%(149/477);母体血清游离β-HCG过低(≤0.5MOM)组,早产等不良妊娠结局发生率为5.12%(29/566);母体血清游离β-HCG正常(0.51～1.99MOM)组中,早产等不良妊娠结局的发生率为1.49%(32/2147)。经Spearman相关性分析,母体血清游离β-HCG水平过高与早产、死胎、肢体畸形、染色体异常等不良妊娠结局的发生显著正相关;母体血清游离β-HCG水平过低与染色体异常发生显著负相关。结论:中孕期孕妇血清游离β-HCG水平过高,与早产、死胎、肢体畸形的发生相关。中孕期孕妇血清游离β-HCG水平过高或过低均提示胎儿患染色体疾病的风险增高。     

Additional benefits of first trimester screening

The goal of first trimester screening for aneuploidy is to provide patients their risk assessment for fetal Down syndrome. Nonetheless, it has been noted that combined screening offers physicians and patients other important pregnancy information. For example, first trimester ultrasound results in accurate pregnancy dating and enables the early diagnosis of multiple gestations during the period when amnionicity and chorionicity is best discerned. It also detects a limited number of fetal anatomical abnormalities, affording patients time to make decisions regarding the management of their pregnancies. A cystic hygroma, one of the most powerful ultrasound markers for fetal aneuploidy, can be detected on first trimester ultrasound. An enlarged nuchal translucency may identify fetuses at risk for other adverse outcomes and for congenital heart defects. In addition, abnormal first trimester serum markers are associated with adverse pregnancy outcomes, and knowledge of these abnormalities may help with patient counseling and management.     

Uterine artery Doppler in the prediction of adverse pregnancy outcome

PURPOSE OF REVIEW: To review publications, published during the past year, that have examined uterine artery Doppler findings in women with adverse pregnancy outcome. RECENT FINDINGS: Almost two-thirds of stillbirths that occur in the early preterm period (up to 32 weeks) can be predicted by uterine artery Doppler at 23 weeks. First trimester screening studies have shown that an abnormal result increases the risk of subsequent fetal growth restriction, and such women are at particularly high risk when indices remain abnormal in the second trimester. Studies combining uterine artery Doppler with maternal serum markers have demonstrated that measurement of first-trimester maternal serum pregnancy-associated plasma protein A and free beta human chorionic gonadotrophin improve sensitivities of second-trimester Doppler. As these are frequently measured in Down syndrome screening and they lend themselves in screening for pre-eclampsia. Women with abnormal first and second-trimester serum markers constitute a high-risk group. Maternal serum placental protein 13 remains a promising method for early screening, although a recent study suggests lower sensitivities than initially reported. SUMMARY: Uterine artery Doppler screening identifies women at high risk for developing adverse pregnancy outcomes. Detection rates may be increased and false positive rates reduced by combination with maternal characteristics or serum markers.     

The efficacy of first-trimester PAPP-A and free beta hCG levels for predicting adverse pregnancy outcome

OBJECTIVE: To determine whether first-trimester measurements of maternal serum PAPP-A and free beta hCG levels were associated with adverse pregnancy outcomes. STUDY DESIGN: First trimester maternal serum free beta hCG and PAPP-A were measured in 490 singleton pregnancies. Pregnancies were followed by the fetal-maternal unit, and predictive efficacy of these markers for small for gestational age (SGA) babies, gestational diabetes mellitus and hypertensive disorders were analyzed by cut-off values determined by using a ROC analysis, and also, by using the fifth percentile as the cut-off value. RESULTS: The sensitivities for PAPP-A in predicting pregnancies with a SGA baby and those complicated by a hypertensive disorder were 49% and 73%, respectively, when optimal cut-off values were used. Specificities were 76% and 65%, respectively. Serum free beta hCG had no predictive value for individual pregnancy outcomes. CONCLUSION: Efficacy of first trimester maternal serum markers in predicting adverse pregnancy outcome is low. Even after optimization of cut-off values, these markers do not appear to be clinically acceptable as an effective tool for screening for adverse pregnancy outcomes.     

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。     

Combinations of maternal serum markers to predict preeclampsia, small for gestational age, and stillbirth: a systematic review

ObjectiveAbnormal serum screening markers have been associated with adverse pregnancy outcomes. We sought to review the performance of combined abnormal first and/or second trimester maternal serum markers used in prenatal screening for aneuploidy and open neural tube defects for predicting preeclampsia (PET), small for gestational age (SGA), and stillbirth beyond 24 weeks’ gestation.Data Sources and Study SelectionMedline, EMBASE, and Cochrane Library databases were searched for studies from 1970 to May 2010 that analyzed predictive abilities of combined serum markers for defined outcomes.Data Extraction and SynthesisData were extracted independently by two authors, and 15 studies were included. Eight studies of 115 290 pregnancies, 11 studies of 144 853 pregnancies, and seven studies of 80 274 pregnancies examined PET, SGA, and stillbirth respectively. Because of the heterogeneity of marker combinations and thresholds, outcome definitions, and analytic methods, limited meta-analysis was possible for the outcomes of PET and SGA only. Three relatively homogeneous studies on prediction of PET, and two on prediction of SGA were meta-analyzed. Several single studies demonstrated utility in combining markers to predict adverse outcome; however, this effect was not confirmed after metaanalysis. The most common combination of markers evaluated was alpha fetoprotein and human chorionic gonadotrophin for all outcomes. The highest positive likelihood ratios for predicting PET (5.68; 95% CI 0.73 to 43.97) and SGA (6.18; 95% CI 1.84 to 20.85) were seen with combined alpha fetoprotein and human chorionic gonadotrophin (> 2.5 multiples of the median).ConclusionsCurrently, no identifiable combination of serum markers performs well as a screening test for preeclampsia, small for gestational age, and stillbirth beyond 24 weeks. Large cohort studies with standardized screening test parameters and outcomes are needed.     

First-trimester biochemical markers for Down syndrome

The value of maternal serum pregnancy-associated protein A (PAPP-A), free and total beta human chorionic gonadotrophin (fbetahCG, betahCG) and alpha-fetoprotein (AFP) in screening for Down syndrome (DS) in early pregnancy has been assessed. To evaluate the different biochemical markers, 32 DS pregnancies and 267 controls were used for AFP, betahCG and PAPP-A. A subgroup of those (17 DS and 136 controls) were used to evaluate fbetahCG. All analytes were determined in fresh serum samples. Our results give support to the feasibility of maternal serum levels of PAPP-A as the best biochemical marker for DS in the first trimester, and either betahCG or fbetahCG as the second marker. No differences were found between betahCG and fbetahCG distribution levels as expressed as MoMs in normal and DS pregnancies in this study.     

妊娠合并恶性肿瘤14例临床分析

目的探讨妊娠合并恶性肿瘤患者的临床特点及母儿结局。 方法收集2009年10月至2015年12月就诊于广州医科大学附属第三医院妇产科的14例妊娠合并恶性肿瘤患者的临床资料,对患者的临床特点、孕期治疗、妊娠结局及预后进行分析。 结果14例妊娠合并恶性肿瘤患者的肿瘤类型分别为血液系统恶性肿瘤(8例)、乳腺癌(4例)和宫颈癌(2例)。足月分娩者有5例,早产6例,1例早期人工流产,1例中孕期引产,1例孕期死亡。共分娩新生儿11例,2例乳腺癌患者于孕期接受抗癌治疗,2例新生儿为足月儿;10例患者孕期选择期待治疗,9例患者的新生儿存活,包括3例足月儿和6例早产儿。 结论妊娠合并恶性肿瘤可导致严重的不良妊娠结局,根据病情孕期应进行合理的抗癌治疗可改善患者结局。     

Advances in antenatal screening for Down syndrome.

Antenatal screening for Down Syndrome using maternal age alone is no longer an adequate standard of care. Screening in the early second trimester of pregnancy (between 15 and 20 weeks of pregnancy) using the quadruple test can identify 76% of affected pregnancies with a 5% false-positive rate. Screening in the first trimester of pregnancy (between 10 and 13 weeks of pregnancy) is possible using two biochemical markers (PAPP-A and free beta-hCG) together with an ultrasound marker nuchal translucency measurement; using these three markers together with maternal age can identify 85% of affected pregnancies, with a 5% false-positive rate. While there is debate over issues involved in choosing between first and second trimester screening, the most effective screening test for Down Syndrome is the integrated test based on the integration of the first trimester and the second trimester markers. This has a 94% detection rate for a 5% false-positive rate. If the false-positive rate were set at 1%, the detection rate would be 85%. No other screening test for Down Syndrome can detect such a high proportion of affected pregnancies with such a low false-positive rate.     

Uterine artery Doppler ultrasound in second pregnancy with previous elective cesarean section*

Objectives: To assess the effects of previous cesarean delivery (CD) and placental location on second trimester uterine artery Doppler indices in subsequent pregnancy and to assess the predictive values of abnormal Doppler findings for adverse pregnancy outcomes in women with previous CD.

Study design: This prospective cohort study evaluated 400 gravida two pregnant women (200 with previous none medically indicated CD and 200 with previous normal vaginal deliveries (NVD)) who were referred for second trimester fetal anatomic survey. Uterine artery Doppler studies were performed in all participants who were then followed until delivery.

Results: Compared with women having prior NVD, women with prior CD had significantly higher rates of abnormal uterine artery pulsatility index (PI) (p?p?=?.01). Among women with previous CD, all the measured adverse pregnancy outcomes occurred significantly more often in women with abnormal uterine artery Doppler indices (p?Conclusions: CD seems to be associated with increased risks of impaired placental function and circulation and adverse pregnancy outcomes in the subsequent pregnancy, particularly in women with anteriorly located placenta near the previous uterine scar.