26 803例中期妊娠妇女血清筛查胎儿染色体异常的结果分析

目的 评价江苏省以人群为基础的中期妊娠母血清筛查胎儿染色体异常的效率。方法 采用分层抽样和整群抽样相结合的多阶段抽样方法,在江苏省苏南、苏中、苏北地区以乡（镇）或街道为单位,抽取95个项目点,抽样时间为1年。项目点所有妊娠15-20周的妇女接受母血清甲胎蛋白（AFP）、人绒毛膜促性腺激素游离β亚单位（f-βHCG）检测,同时B超确定孕龄,在孕妇体重校正的基础上,计算胎儿染色体异常的风险值。对高风险者,在知情同意的基础上进行确诊检查。随访所有活产儿至出生后的0．5～4岁。结果 95个项目点1年中共有妊娠妇女27313名,参与产前筛查者26803例,占同期总妊娠妇女的98％。孕妇平均年龄25．1岁,≥35岁者占1．7％。母血清筛查为唐氏综合征高风险者1244例、爱德华综合征高风险者105例,筛查阳性率分别占筛查人群的5％、0．4％。最终妊娠结局显示染色体异常胎儿及婴幼儿共20例,其中唐氏综合征9例、爱德华综合征5例,其他染色体异常6例。本组中期妊娠母血清AFP、f-βHCG联合筛查唐氏综合征的检出率为56％（5／9）,爱德华综合征检出率80％（4／5）。结论 在严格质量控制的基础上,妊娠中期母血清AFP、f-βHCG二联筛查胎儿染色体异常有较高的检出率,但良好的筛查成本效益比与目标出生缺陷的人群发病率有关。     

妊娠中期母血清唐氏综合征三联筛查4 680例与不良妊娠结果分析

Currentlythetriplemarkerscreenoffetoprotein(AFP),unconjugatedestriol(uE3)andhumanchori onicgonadotropin(hCG)testcandetectapproximately60%(58%-82%)ofthepregnanciesaffectedbytri somy21,withafalsepositiverateofabout5%-10%[1].Currentlyprenatalscreeningforfeta…     

Comparison of second-trimester maternal serum free-β-human chorionic gonadotropin and α-fetoprotein between normal singleton and twin pregnancies: a population-based study

Background  The second-trimester maternal serum screening in twin pregnancy is still controversial, as the serum marker levels in twins are not as clear as those in singletons. This study aimed to evaluate the relationship between the levels of the second-trimester maternal serum free β-human chorionic gonadotropin (free β-HCG) and α-fetoprotein (AFP) in normal twin and singleton pregnancies and to estimate feasible analysis methods for utilizing these markers in second trimester screening for twin pregnancy.
Methods  On the basis of a prospective population-based study of second-trimester maternal serum screening, the concentrations of maternal serum AFP and free β-HCG of 195 normal twin pregnancy and 26 512 singleton controls at gestational weeks 15 to 20 were measured by time-resolved fluoroimmunoassay in one laboratory. The levels of markers were compared between the twins and singletons using weight-correction and gestational age-specific model.
Results  According to the research protocol, 95 communities were randomly sampled, which covered the whole Jiangsu province, the east of China. A total of 26 803 pregnant women (98%), from the target population accepted prenatal screening for maternal serum AFP, β-HCG detection, and all babies were followed up for at least six months. There were 197 (0.73%) twin pregnancies, of which one case had fetal trisomy 18, and one case with fetal anencephaly. The others were normal twin pregnancy. From a total enrollment of 26 803 women participants, 26 512 women with normal singleton pregnancies were selected as the model controls. The other 291 pregnancies, including trisomy 21, neural tube defect (NTD), trisomy 18, and other fetal abnormalities, were excluded. No significant differences were found in the medians of gestational age-specific maternal serum free β-hCG and AFP in normal twin pregnancy comparing with twice those in model controls with the exception of the medians for free β-hCG during the 16th gestational week (P=0.012).
Conclusion  The weight-correction and gestational age-specific levels of Chinese Han population maternal serum free β-hCG and AFP in normal twins were twice the levels as those in the singleton controls during the 17–19 gestational weeks.

     

孕中期母血唐氏筛查分析与遗传咨询

目的探讨孕中期母血唐氏筛查及异常妊娠的临床价值。方法采集孕中期(16～20周)母血,以美国Zymed孕中期唐氏综合征产前筛查试剂盒检测血清AFP和β-HCG,结合母龄、孕周、体质量等,采用软件综合计算胎儿染色体病的发病风险。对高风险孕妇行羊水细胞或脐带血细胞核型分析以确诊,并跟踪到胎儿出生。同时,将孕妇分为≥35和﹤35周岁组,唐氏阳性和阴性组,分别对其筛查结果和不良妊娠进行分析。结果共筛查6000例,552例阳性,漏检1例,阳性率约9.2%,接受羊水或脐带血穿刺者463例(84%),胎儿有染色体异常者共27例,建议终止妊娠者14例,其余13例为染色体多态性变异。≥35和﹤35周岁两组孕妇筛查阳性率分别是95.5%和8.2%(P<0.0001),其胎儿染色体异常率分别是4.5%和2.9%(P>0.5);筛查阳性和阴性两组中妊娠不良结局发生率分别为5.6%和0.05%(P<0.0001),妊娠并发症发生率分别率分别为11.8%和3.7%(P<0.0001),胎儿染色体多态性发生率分别为2.8%和1.1%(P>0.5)。结论孕中期血清AFP和β-HCG联合检测,对于预测胎儿染色体病具有重要临床价值,可有效降低染色...     

1502例孕中期孕妇产前三联筛查结果分析

目的探讨应用母亲血清标志物检查筛查胎儿唐氏综合征的临床价值。方法应用ACCESS全自动免疫化学发光仪及配套试剂对妊娠15—22周的1502例孕妇进行血清AFP、β-hCG、μE3的测定,风险率〉1：380定为筛查阳性,再作羊水检查进行产前诊断。结果1502例孕妇中筛查为阳性者47例（3．13％）,接受产前诊断者45例,有3例21-三体核型胎儿,2例神经管畸形胎儿,1例18-三体综合征胎儿。结论孕中期应用母亲血清生化指标筛查唐氏综合征胎儿并结合产前诊断是减少唐氏综合征患儿出生的有效方法。     

产前筛查母血清标志物与产科并发症关系的研究

目的通过对孕中期（孕15～20周）母血清中游离β-hcG和AFP检测,研究血清标志物与某些产科并发症的关系,以期早期发现,早期诊断产科并发症。方法对妊娠15～20周孕妇,抽取静脉血,检测AFP和fβ-hcg。结果当游离β-hcGMoM值≥2.0时,孕中期高水平AFPMoM值与早产、低体重儿、前置胎盘、新生儿窒息有关;当AFPMoM值在0.5～2.0时,孕中期高水平fβ-hcGMoM值与羊水过少,羊水污染,过期妊娠,胎窘,胎盘植入有关;当游离β-hcGMoM值在0.5～2.0时,孕中期高水平AFPMoM值与重度子痫前期、胎膜早破、前置胎盘有关。结论孕中期高水平血清标志物与一些产科并发症如早产、低体重儿、前置胎盘、胎盘植入、胎膜早破、羊水过少、羊水污染、胎儿宫内窘迫、新生儿窒息、子痫前期有关。     

四川地区21 723例早孕期唐氏综合征筛查报告

  目的  比较分析采用不同筛查方案对四川地区早孕期孕妇进行唐氏综合征产前筛查的筛查效率,探寻早孕期高效的唐氏综合征筛查方案。  方法  回顾性分析2011年1月至2017年12月于四川大学华西第二医院产前诊断中心接受早孕期血清学生化指标联合胎儿颈项透明层（NT）厚度筛查的单胎妊娠孕妇的结果。根据接受羊膜腔穿刺胎儿染色体检查的染色体结果及未接受羊膜腔穿刺的孕妇电话随访结果,了解胎儿染色体情况。比较分析孕妇年龄、NT厚度、血清学生化指标筛查、联合筛查这4种筛查方案对早孕期唐氏综合征的筛查效率。  结果  符合纳入标准的21 723例孕妇中,确诊唐氏综合征33例,18-三体综合征19例,性染色体异常4例及其他染色体异常8例。早期联合筛查唐氏综合征检出率72.73%,假阳性率2.49%;18-三体综合征检出率73.68%,假阳性率0.39%。对唐氏综合征而言,当假阳性率为5%时,以孕妇预产期年龄为筛查指标时,检出率为15.15%;以NT厚度为筛查指标时,检出率为57.58%;以早孕期血清学生化指标作为筛查方案时,检出率为60.61%;以早孕期联合筛查作为筛查方案时,检出率为87.88%。  结论  4种筛查方案中,早孕期联合筛查能够有效筛查出唐氏综合征胎儿,对其他染色体异常也有良好的筛查效果,是早孕期较好的产前筛查方案。     

AFP对杭州地区神经管缺陷孕中期筛查的作用

目的分析杭州地区孕中期妇女运用甲胎蛋白(alpha fetoprotein,AFP)在妊娠中期筛查胎儿神经管缺陷(neural tube defect,NTD)的结果;并据此修正筛查指标的孕周中位数值。方法对杭州地区孕14~20周的妇女进行产前AFP检测。胎儿先天畸形经B超检查确诊或引产证实。应用非线性加权回归求得本地区筛查指标的中位数,并计算中位倍数值进行分布拟合。比较标化前后检测效果。结果8516例孕妇中,检出NTD高风险55例,筛查阳性率为0.65%(55/8516),都进行三维彩超诊断,发现异常7例,均引产证实。杭州地区孕中期妇女AFP中位数比欧洲妇女高18%;用修正后的中位数重新分析,孕中期假阳性率降低。结论孕中期血清AFP检测,可作为孕中期神经管缺陷筛查优选项目。而根据地域人群的差异,对MultiCalc软件内嵌中位数进行修正后更适于杭州地区孕中期妇女的产前筛查。     

母血清生化二联、三联标记物筛查胎儿唐氏综合征

目的 用母血清生化标记物筛查胎儿唐氏综合征(Down’s syndrome,DS)等先天异常。方法 应用孕妇血清指标和时间分辨荧光免疫分析法对本院1996年11月-2001年3月在本科产前检查的2886例孕妇进行DS胎儿筛查。对高危孕妇作羊腹腔穿刺或早孕绒毛取材以得到胎儿染色体。对应用的指标捡出率及假阳性率进行分析。结果 共捡出11例DS,8例无脑儿;DS检出率3．8‰。结论 妊娠相关血浆蛋白A(PAPP-A)筛查胎儿DS有很好的价值并能使产前诊断时期提前,甲胎蛋白 游离人绒毛膜促性腺激素(AFP freeβ-HCG)可用于检测DS和胎儿异常。     

三维超声结合母血清生化指标在中孕期胎儿筛查中的价值

目的 探讨三维超声结合母血清生化指标在中孕期胎儿筛查中的价值.方法　对中孕期胎儿分系统进行三维超声检查,再结合母血清中甲胎蛋白(AFP)、人绒毛膜促性腺激素β亚基(Free-βHCG),诊断胎儿畸形情况,并与引产或出生后的胎儿对照分析.结果 1108例中孕期胎儿三维超声检查结构异常15例,漏诊5例,误诊2例.1108例母血清生化指标检查,唐氏综合征高风险123例,18例行羊水检查,其中唐氏综合征高风险6例.1108例中神经管畸形高风险者49例.两种检查方法比较,有统计学意义.结论　该方法有效地减少胎儿畸形的漏诊和误诊,提高患者的满意率,最大限度地减少医疗纠纷,减低医疗风险,减轻医生的压力.     

931例孕妇唐氏综合征产前筛查结果分析

目的了解孕中期产前筛查干预胎儿唐氏综合征的作用。方法采用时间分辨荧光免疫法,检测孕妇血清中AFP和Free-β-HCG的浓度,结合孕妇年龄、孕周、体重等因素,配套软件分析胎儿患唐氏综合征的风险率,高风险孕妇遗传咨询、产前诊断。结果筛查931例孕妇,唐氏综合征高危52例,阳性率5.6%,开放性神经管缺陷高危4例,阳性率0.4%。结论孕中期母体血清标记物联合检测、分析,对防止唐氏儿出生、降低出生缺陷具有重要作用。     

茂名市9368例唐氏综合征产前筛查结果分析

目的了解茂名市产前诊断中心的唐氏综合征产前筛查和产前诊断情况,分析目前产筛存在的问题。方法孕早期筛查采用时间分辨荧光免疫分析法测定血清标志物游离β-人绒毛膜促性腺激素(Freeβ-HCG)和妊娠相关蛋白A(PAPP-A)的浓度,孕中期筛查采用化学发光免疫分析仪测定血清标志物AFP、T-βHCG、μE3的浓度,结合孕妇年龄、体重、孕周等因素,经过配套筛查软件进行风险评估,筛查出高风险对象通过B超和羊水细胞学染色体核型分析确诊,杜绝缺陷胎儿出生。结果9 368例唐氏综合征产前筛查中,查出唐氏综合征高危产妇403例,筛查阳性率为4.30%,经染色体分析确诊唐氏儿6例,18-三体高风险者92例,筛查阳性率为0.98%,经染色体核型分析确诊2例,神经管缺陷高危者62例,筛查阳性率为1.10%,最终确认神经管缺陷胎儿13例。结论唐氏综合征产前筛查和产前诊断可有效降低缺陷胎儿的出生,对优生优育,提高人口素质有重要的意义。     

6.1.3.2 Quality Specifications for S-AFP and S-HCG-β Determinations for Screening of Fetal Abnormalities

High levels of maternal serum α-l-fetoprotein (S-AFP) are associated with fetal structural abnormalities like neutral tube defects and congenital nephrosis. It has a very high detection rate (3,4,5,6) when used for screening of these diseases. On the other hand, the low levels of maternal S-AFP act as a marker of many fetal chromosomal aberrations (2,3,4,8). The detection rate of S-AFP alone for the screening of Down's syndrome is low. Wald et al. (8) have shown that the addition of the determination of maternal serum chorionic gonadotrophin (S-HCG-B) to S-AFP analysis, and using a computer program for risk estimation increases the detection rate for Down's syndrome to about 57% (2) with a false positive rate of 5%. In this study we present the results of our screening program for structural fetal defects and chromosomal aberrations in Eastern Finland, and describe the standardization and quality control of maternal serum AFP and HCG-β analysis.     

鼻前软组织厚度产前筛查唐氏综合征的临床价值

目的 通过超声检测胎儿鼻前软组织厚度(PT),探讨鼻前软组织厚度与唐氏综合征(DS)的关系,建立超声软指标PT中位倍数(MoM)值,明确PT筛查唐氏综合征的临床价值。 方法 对2012年6月—2014年6月期间在温州市中心医院超声检查的孕16～25周的正常胎儿及DS胎儿进行PT测量,组间比较采用t检验或Wilcoxon秩和检验,并行Spearman线性相关分析,采用二次回归模型计算2组MoM(PT)值,并建立风险评估模型,观察敏感度、特异度、阳性预测值、阴性预测值、阳性似然比、阴性似然比指标。 结果 正常组PT平均值为(3.51±0.91) mm,DS组PT平均值为(5.16±0.79) mm,差异有统计学意义(t=12.23,P＜0.05);正常组胎儿PT随孕周增加而增厚,正常胎儿PT的MoM值为1.010,DS胎儿PT的MoM值为1.371。PT为单一指标筛查DS,以5%假阳性率,筛查唐氏综合征胎儿敏感度为58%,阳性预测值为0.46,阴性预测值为0.97,阳性似然比为11.63,阴性似然比为0.44;PT联合年龄高风险筛查DS,以5%假阳性率,敏感度提高到75%,阳性预测值为0.52,阴性预测值为0.98,阳性似然比为14.94,阴性似然比为0.26。 结论 鼻前软组织厚度是孕中期筛查唐氏综合征有效的遗传学超声软指标,唐氏综合征胎儿鼻前软组织厚度较正常胎儿厚。鼻前软组织厚度联合年龄高风险筛查唐氏综合征可以提高筛查敏感度,风险截断值达1/250,应建议行侵入性检查。      

胎儿颈部软组织厚度及母体血清标记物筛查胎儿异常效果

目的探讨胎儿颈部软组织厚度和母体血清标记物在筛查胎儿发育异常的价值。方法收集399例孕11～14周超声测定胎儿颈部软组织（nuchal translucency,NT）厚度和1125例孕14-21周测定母体二联血清标记物（AFP＋Free—B—HCG）,并对其胎儿结局进行追踪。结果胎儿NT测定和母体血清标记物用于筛查胎儿发育异常的敏感度分别为50．00％和51．11％,特异度分别为98．69％和74．44％。胎儿NT筛查胎儿发育异常的截断值初步计算为2．25mm。结论胎儿NT和母体血清标记（AFP＋Free—β—HcG）筛查胎儿发育异常具有较高的敏感性。     

唐氏高风险胎儿孕中期超声筛查的研究分析

目的探讨孕中期超声筛查在诊断唐氏高风险胎儿中的作用和意义。方法对15~20周孕妇抽血进行血清标记物甲胎蛋白(AFP)、β绒毛膜促性腺激素(β-hCG)筛查,以1:300为切割值,对唐氏高风险者建议孕中期超声筛查及羊膜腔穿刺。结果血清筛查唐氏高风险682例,其中184例同意羊水穿刺,发现21三体4例,阳性率2.17%。孕中期超声筛查635例,发现胎儿异常标记37例,异常检出率5.83%。其中21例分娩,16例引产。结论孕中期超声筛查可检出胎儿结构畸形和软指标异常,联合血清标记物和羊水穿刺可有效减少唐氏儿的出生。     

孕中期AFP,UE_3,β-HCG联合筛查唐氏综合征临床分析

[背景]探讨孕中期唐氏综合征产前筛查的方法及影响其风险值的主要因素.[病例报告]采用全自动化学发光免疫分析仪检测950例孕14～20周孕妇血清甲胎蛋白(AFP)、游离雌三醇(UE3)及人绒毛膜促性腺激素β-亚单位(β-HCG)值,应用美国贝可蔓公司提供的软件对AFP,UE3,β-HCG值进行风险分析,以风险比1∶380为切割点,判断950例孕中期胎儿的风险情况.风险比高于1∶380以上者为10例,其中5例进行了羊水穿刺,经染色体核型分析确诊1例,待分娩后确诊其余胎儿均为阴性,在高危孕妇中阳性率为10.0%.[讨论]上述3个指标联合筛查为较理想的产前唐氏综合征筛查模式.     

唐氏综合征筛查指标MoM值的正态性研究

目的: 考察江苏唐氏综合征产前筛查指标AFP和HCG的MoM值的正态性,探索Johnson分布体系中的SL分布族在上述指标正态性转换中应用的可行性和有效性. 方法: 资料来自于江苏省出生缺陷干预项目研究,采用对数正态和Johnson分布体系中的SL正态性转换方法. 结果: 两指标的MoM值均不服从正态分布;对数MoMHCG值以样本均数和标准差作为参数时,指标AFP的正态性较好,HCG仍不服从正态;Z=0.31时MoM指标SL转换后正态性明显改善. 结论: Johnson分布体系中SL分布族在我国唐氏综合征产前筛查指标HCG的MoM值的正态性转换中具有一定的应用价值.     

Second-trimester ultrasound to detect fetuses with Down syndrome: a meta-analysis

CONTEXT: Second-trimester prenatal ultrasound is widely used in an attempt to detect Down syndrome in fetuses, but the accuracy of this method is unknown. OBJECTIVE: To determine the accuracy of second-trimester ultrasound in detecting Down syndrome in fetuses. DATA SOURCES: English-language articles published between 1980 and February 1999 identified through MEDLINE and manual searches. STUDY SELECTION: Studies were included if they recorded second-trimester findings of ultrasonographic markers, chromosomal abnormalities, and clinical outcomes for a well-described sample of women. A total of 56 articles describing 1930 fetuses with Down syndrome and 130 365 unaffected fetuses were included. DATA EXTRACTION: Articles were independently reviewed, selected, and abstracted by 2 reviewers. Discrepancies in data abstraction were resolved by consensus with a third reviewer. Overall estimates of sensitivity, specificity, and positive and negative likelihood ratios were calculated for the following markers: choroid plexus cyst, thickened nuchal fold, echogenic intracardiac focus, echogenic bowel, renal pyelectasis, and humeral and femoral shortening. Results were stratified by whether markers were identified in isolation or in conjunction with fetal structural malformations. DATA SYNTHESIS: When ultrasonographic markers were observed without associated fetal structural malformations, sensitivity for each was low (range, 1%-16%), and most fetuses with such markers had normal outcomes. A thickened nuchal fold was the most accurate marker for discriminating between unaffected and affected fetuses and was associated with an approximately 17-fold increased risk of Down syndrome. If a thickened nuchal fold is used to screen for Down syndrome, 15 893 average-risk women or 6818 high-risk women would need to be screened for each case of Down syndrome identified. For each of the other 6 markers, when observed without associated structural malformations, the marker had marginal impact on the risk of Down syndrome. Because the markers were detected in only a small number of affected fetuses, the likelihood of Down syndrome did not decrease substantially after normal examination findings (none of the negative likelihood ratios were significant). CONCLUSIONS: A thickened nuchal fold in the second trimester may be useful in distinguishing unaffected fetuses from those with Down syndrome, but the overall sensitivity of this finding is too low for it to be a practical screening test for Down syndrome. When observed without associated structural malformations, the remaining ultrasonographic markers could not discriminate well between unaffected fetuses and those with Down syndrome. Using these markers as a basis for deciding to offer amniocentesis will result in more fetal losses than cases of Down syndrome detected, and will lead to a decrease in the prenatal detection of fetuses with Down syndrome.     

江西省中北部地区孕中期唐氏综合征筛查血清标志物中位数的构建

目的：建立江西省中北部地区孕中期唐氏综合征(Down’s syndrome,DS)产前筛查血清学标志物中位数数据 库。方法：采用时间分辨免疫荧光法对57 548例孕15~20+6周孕妇进行甲胎蛋白(AFP)、游离绒毛膜促性腺激素(β-hCG) 和游离雌三醇(uE3)血清学三联筛查,应用LifeCycle 4.0软件进行风险评估。使用SAS 9.2软件进行模型筛选,构建江西 省中北部地区孕中期DS筛查人群中位数拟合方程,采用新构建的中位数系统重新评估人群患DS风险,并评估其适用 性。结果：江西省中北部地区中位数与内置中位数分布不同,差异有统计学意义(Z=2.201,P=0.028),经模型筛选, 三联指标中位数与孕龄的关系采用加权回归模型拟合,三联指标中位数倍数(MoM值)与体重的关系采用倒数模型, 拟合效果好;新构建的中位数系统较内置系统检出率由62.75%提高到72.55%,假阳性率由5.84%降低至4.94%。结论： 新构建的江西省中北部地区孕中期中位数系统适用于本地区筛查,各地区应建立自己的血清标志物中位数系统以提 高筛查效率。