9例18三体综合征胎儿的产前诊断

目的探讨利用孕妇血清筛查和胎儿超声筛查进行18三体综合征胎儿产前诊断的有效性。方法对36例首诊主诉为产前筛查胎儿18三体高危、92例首诊主诉为胎儿超声有异常发现的孕18~32周孕妇共128例，进行羊膜腔穿刺羊水细胞培养、或脐血管穿刺脐血细胞培养染色体分析。结果128例胎儿核型中，9例为18三体综合征，2例为其它染色体异常，染色体异常发现率为8．59％（11／128）。首诊主诉为18三体高危发现18三体4例，异常发现率11．11％（4／36）；首诊主诉胎儿超声异常发现18三体5例，其它染色体异常2例，异常发现率7．61％，其中2例18三体合并有筛查高危和超声异常。结论孕妇血清生化指标筛查结合胎儿超声检查是产前检出18三体胎儿的有效筛查手段。     

多重连接依赖探针扩增技术检测胎儿非整倍体染色体异常

目的 探讨多重连接依赖探针扩增技术(multiplex ligation-dependent probe amplifiea-tion,MLPA)在检测胎儿非整倍体染色体异常中的作用. 方法 2007年6月至2008年12月对263例需进行产前诊断的孕妇(产前诊断组)取羊水或脐血进行MLPA检测,同时进行传统的染色体核型分析.对26例发生稽留流产或死胎的孕妇取胎儿组织提取DNA进行MLPA检测. 结果 产前诊断组检出5例21-三体,4例18-三体,1例13-三体和3例45,X,与细胞核型分析结果一致.稽留流产或死胎组检出2例45,x和1例18-三体. 结论 MLPA可用于检测胎儿最常见的13、18、21、X、Y染色体非整倍体异常,用于产前诊断,快速简单,准确经济,有一定的临床推广价值.     

247例妊娠中期孕妇羊水细胞染色体核型分析

目的 分析妊娠中期进行产前诊断的孕妇羊水细胞染色体核型，了解此期异常核型发生的频率、类型及与各种产前诊断指征的关系。方法 对247例妊娠中期孕妇行羊膜腔穿刺术抽羊水作羊水细胞培养检查染色体核型。结果 发现异常核型14例，异常核型出现频率为5．67％，其中三体型7例，占异常核型的50％，分别为21三体4例，18三体2例，13三体1例；其次为平衡易位6例，占42．86％。高龄孕妇中21三体检出率为5．56％(1／18)，非高龄组为1．31％(3／229)，P=0．235，差异无显著性。15例产前常规B超检查发现胎儿发育异常的孕妇中，检出三体儿3例。结论 在有各种产前诊断指征的妊娠中期孕妇中，胎儿染色体异常发生率为5．67％，染色体三体为主要的异常核型。孕中期B超检查做为产前常规筛查可提高胎儿染色体异常的检出率。     

妊娠早期胎儿染色体异常的超声检查

新生儿出生缺陷主要包括染色体异常和结构异常。染色体异常中最常见的是21-三体畸形（Down’s综合征），18-三体畸形，13-三体畸形和45-XO畸形（Turner综合征），染色体异常胎儿的围产死亡率高，出生后的新生儿可以伴有脏器结构异常、智力障碍、生育能力降低等。国内外学者对胎儿缺陷的产前诊断已经进行了多方面的研究，有些已在临床上广泛应用。在这些筛查方法中脐血、羊水中胎儿脱落细胞及早期妊娠绒毛细胞的培养进行染色体核型分析已经被证明是染色体异常诊断的肯定方法，但这些检查均为有创性操作，具有一定的流产风险性。无创性而有效的产前筛查方法是国内外学者们探索的方向。目前，对胎儿染色体异常的筛查主要是在妊娠14周以后通过联合血清学筛查，并结合超声检查进行综合评价。随着医疗技术水平的不断提高，     

胎儿游离DNA用于无创产前检测21、18、13三体综合征的临床研究

目的探讨孕妇外周血中胎儿游离DNA在无创产前诊断21、18、13三体综合征的临床意义。方法收集2012年1月至2013年12月在广州医科大学附属第二医院妊娠11~32周进行无创产前检测的单活胎孕妇433例,提取胎儿游离DNA,制备测序文库,应用大规模平行测序技术,获得胎儿患染色体三体综合征的风险,并将无创结果与核型分析及分娩结局进行分析。结果 433例无创产前检测孕妇中,胎儿游离DNA高风险9例,其中21三体6例,18三体1例,13三体1例,Turner综合征1例,均与羊水/脐血培养细胞染色体核型分析结果相符;成功随访374例,5例因非染色体原因终止妊娠,369例成功分娩,新生儿外貌及智力发育未发现明显异常,其中6例新生儿外周血细胞染色体核型分析与无创结果相符。结论在孕妇中采用无创产前检测21、18、13三体综合征是可行的,可有效降低后续的侵入性产前诊断的数量,值得临床推广应用。     

无创产前基因检测在胎儿染色体非整倍体筛查中的应用研究

目的:探讨无创产前基因检测(NIPT)在胎儿染色体非整倍体疾病诊断中的临床应用价值及意义。方法:收集2016年1月至2016年12月在我院行NIPT检测的6030例单活胎孕妇(孕12~32周)外周血标本并提取胎儿游离DNA,进行文库构建后利用高通量测序技术,结合生物学信息分析,推算出胎儿患染色体疾病的风险率。对检测结果提示高风险者建议行羊水或者脐血穿刺及染色体核型分析;对检测结果低风险者进行电话跟踪随访。结果:行NIPT检测的6030例孕妇检出高风险67例,其中21-三体高风险16例,18-三体高风险3例,13-三体高风险5例,性染色体异常高风险34例,其他染色体异常高风险9例。67例高风险孕妇中,10例拒绝进一步产前诊断,余57例均行羊水/脐血穿刺检查,其中确诊胎儿染色体异常34例(21-三体16例,18-三体2例,13-三体2例,性染色体异常12例,其他染色体异常2例);余23例羊水/脐血穿刺结果正常者,继续妊娠。NIPT对21-三体和18-三体的阳性预测值达100.00%和66.67%,但对13-三体、性染色体异常以及其他染色体异常的阳性预测值仅50.00%、42.85%和33.33%。结论:NIPT对21-三体和18-三体的检测符合率较高,但对13-三体、性染色体异常以及其他染色体异常符合率偏低。NIPT是一项筛查技术,测序高风险的孕妇仍需行羊水/脐血穿刺,以保证产前诊断的准确性。     

血清学筛查与胎儿超声检查在18、13三体综合征产前诊断中的应用

目的:探讨利用孕妇血清学筛查和胎儿超声检查进行18、13三体综合征胎儿产前诊断的有效性。方法:①对78例(A组)产前血清学筛查18、13三体高风险孕妇,拒绝进行产前诊断的孕妇进行随访观察。②对56例(B组)首诊主诉胎儿超声检查有结构异常的孕妇、134例(C组)首诊主诉为产前血清学筛查胎儿18三体高风险的孕妇,于孕18～32周行羊膜腔穿刺羊水细胞培养,或脐血管穿刺脐血细胞培养染色体分析。结果:A组的18三体筛查高风险孕妇有2例出现B超检查结构异常而放弃妊娠,1例产后检查新生儿先天性心脏病。B组发现18三体3例,13三体3例,其他染色体异常7例,异常发现率23.21%(13/56);其中2例18三体合并有血清学筛查高风险。C组发现胎儿异常4例,其中2例确诊为18三体,异常发现率2.99%(4/134)。结论:孕妇血清生化指标筛查结合胎儿超声检查是产前检出18、13三体综合征胎儿的有效检查方法。     

3405例产前诊断的指证及其结果评价

目的:分析产前诊断指证与胎儿染色体检测结果的关系。方法:3405例有产前诊断指证的孕妇,进行羊膜腔穿刺或脐静脉穿刺术,取羊水细胞或脐血细胞培养,作胎儿染色体核型分析。结果:3405例孕妇共检出胎儿染色体异常88例,染色体异常率为2.6%,显著高于一般人群的异常率(P<0.01)。其中夫妇一方为染色体平衡易位携带者组的胎儿染色体异常率达25.9%(7/27),产前胎儿超声异常标记组、孕母血清唐氏筛查阳性组和高龄孕妇组的异常率分别为6.2%(49/778)、1.7%(22/1283)和1.1%(7/664)。18-或21-三体儿妊娠史组、体外受精组、本次妊娠有先兆流产史组和孕期不良因素接触组,均未检出胎儿染色体异常。结论:出现胎儿染色体异常率最高的指证,依次为夫妇一方染色体平衡易位携带者、产前超声发现胎儿异常标记、孕母血清唐氏筛查阳性和高龄孕妇。有针对性地进行产前诊断,可有效地控制和减少出生缺陷的发生。     

改良荧光原位杂交技术在产前诊断中的应用

目的:评价改良荧光原位杂交(fluorescent in situ hybridization,FISH)技术在产前诊断中的应用。方法:用改良FISH技术检测119例孕16~24周孕妇的羊水间期细胞及10例孕25~32周胎儿脐血间期细胞,5例孕9~12周绒毛间期细胞,每例均行常规染色体核型分析。结果:应用改良FISH法,所有样本均在6h内获得检测结果,除2例羊水培养失败外,其余样本均在3周内获得细胞遗传学诊断。两种方法均检出特氏综合征、18-三体综合征、21-三体综合征各1例,另5例常规染色体核型分析异常,因超出检测范围,FISH法未能检出,所有样本的两种方法检测结果均一致。结论:经改良后的FISH技术缩短了诊断时间,缓解了孕妇及家属的焦虑心情,且可用于多种不同样本的检测,因其高效、省时、取材多样等优点在产前诊断具有重要的临床价值。     

联合细菌人工染色体微珠技术和染色体核型分析在二孩高龄孕妇产前诊断中的应用研究

目的:探讨联合细菌人工染色体微珠技术(BoBs)和染色体核型分析在二孩高龄孕妇产前诊断中的应用。方法:选择2016年8月至2018年8月在本院遗传咨询门诊、胎儿医学门诊及孕产妇保健门诊就诊的1291例二孩高龄孕妇为研究对象,对羊水细胞的染色体进行核型分析和BoBs分析,对胎儿染色体异常及常见微缺失综合征进行诊断。结果:1291例二孩高龄孕妇羊水样本中,染色体核型分析和产前BoBs均检出染色体异常47例。产前BoBs技术共检测出61例染色体异常,包括30例21-三体,14例18-三体,3例13-三体,14例染色体微缺失/微重复,总体检出率为4.73%,漏检13例,检测失败7例;染色体核型分析检测出60例染色体异常,比BoBs额外检出10例胎儿染色体结构异常,2例低比例的嵌合型染色体以及1例标记染色体,染色体核型分析染色体异常检出率为4.65%;经两者联合检出异常81例,联合检出率为6.27%。染色体核型分析和产前BoBs共同检出的47例二孩高龄孕妇选择了终止妊娠;BoBs漏检的13例胎儿染色体结构异常均为平衡易位或倒位,经遗传咨询后均选择了继续妊娠。BoBs检测失败的7例,经遗传咨询后继续妊娠。染色体核型分析漏检的14例经遗传咨询后均选择了终止妊娠。1291例二孩高龄孕妇均获得随访,其中经染色体核型分析和BoBs检测显示正常的1210例二孩高龄孕妇,胎儿分娩后均为正常健康胎儿;BoBs漏检的13例胎儿染色体结构异常在随访中均未见异常。结论:"核型分析+BoBs"产前诊断模式可以应用于二孩高龄孕妇的产前诊断,值得临床推广和应用。     

The role of fetal echocardiography and genetic sonography in prenatal diagnosis of the Edward's syndrome--analysis of the thirty case diagnosed at the Department of the Diagnosis for Fetal Malformations at the Institute "Polish Mother's Memorial Hospital."

OBJECTIVE: Trisomy 18 (Edward's syndrome) is one of the most common chromosomal aberration in fetuses/neonates. The aim of our study was to assess the usefulness of the fetal echocardiography and genetic sonography in prenatal diagnosis trisomy 18 (retrospective analysis). MATERIAL AND METHOD: Between 1994-2000 at the Institute "Polish Mother's Memorial Hospital" 30 cases of trisomy 18 were diagnosed. RESULTS: Every fetus/neonate presented with congenital anomalies. The most common were: intrauterine growth retardation (96%) and congenital heart defects (92%). CONCLUSIONS: Retrospective analysis indicates the great role of "genetic sonography" and fetal echocardiography in prenatal diagnosis of trisomy 18.     

Choroid plexus cysts in the 2d trimester--an indication for trisomy 18]

The application of high resolution ultrasound in the prenatal diagnosis enables a detailed differentation of the intracerebral structures in the fetus. In a period of 16 months (Jan. 1990-June 1991) we diagnosed at the "Center for prenatal diagnosis and therapy" at the Charité's Hospital in 14 fetuses among 1800 investigated plexus chorioideus cysts. A rapid karyotyping after cordocentesis was performed in 11 cases. In 3 of them a trisomy 18 could be detected. In one fetus having a normal karyotype we could find besides the cysts multiple structural anomalies. In these 4 cases the termination of pregnancy was performed. In the other 10 pregnancies we could observe a spontaneous regression of the plexus cysts. These results suggest that the prenatal diagnosis of plexus chorioideus cysts is a indication for cytogenetic evaluation in order to detect a trisomy 18.     

染色体13／21α卫得探针用于产前诊断21三体综合征

目的：探讨应用染色体13／21α卫星探荧光原位杂交（FISH）技术行产前论断21三体综合征的价值。方法：选择10例经产前细胞遗传学检查证实为孕正常胎儿孕妇的羊水细胞（对照组）、3例证实为21三体胎儿孕妇的羊水细胞（观察组）,用13／21α卫星探针对未经培养的羊水细胞间期核进行FISH杂交,结果：两组总杂交率分别为36．7％和38．6％,差异无显著性（P＞0．05）。对照组和观察组含4个杂交信号的核平均丰分比分别为36．5％和3．9％,含5个杂交信号的核平均百分比分别为4．0％和36．1％,差异有极显著性（P＜0．01）,含5个信号的百分比＜36．1％可作为21三体综合征的诊断标准。结论：13／21α卫星探针间期FISH用于未培养的羊不细胞可以快速,准确地在产前诊断21三体综合征。     

Prenatal diagnosis of dilated coronary sinus with persistent left superior vena cava in a fetus with trisomy 18

A case of dilated coronary sinus with persistent left superior vena cava diagnosed at 33 weeks in a fetus with trisomy 18 is reported. The features of this cardiac anomaly on prenatal ultrasonography and its association with trisomy 18 are discussed. Published in 2003 John Wiley & Sons, Ltd.     

染色体13/21α卫星探针用于产前诊断21三体综合征

目的探讨应用染色体13/21α卫星探针荧光原位杂交（FISH）技术行产前诊断21三体综合征的价值。方法选择10例经产前细胞遗传学检查证实为孕正常胎儿孕妇的羊水细胞（对照组）、3例证实为孕21三体胎儿孕妇的羊水细胞（观察组）,用13/21α卫星探针对未经培养的羊水细胞间期核进行FISH杂交。结果两组总杂交率分别为36.7%和38.6%,差异无显著性（P>0.05）。对照组和观察组含4个杂交信号的核平均百分比分别为36.5%和3.9%,含5个杂交信号的核平均百分比分别为4.0%和36.1%,差异有极显著性（P<0.01）,含5个信号的核百分比＜36.1%可作为21三体综合征的诊断标准。结论 13/21α卫星探针间期FISH 用于未培养的羊水细胞可以快速、准确地在产前诊断21三体综合征。     

3D ultrasound and Doppler angiography for evaluation of fetal cardiovascular anomalies

ObjectiveTo highlight the value of 3D ultrasound in the prenatal assessment of fetal cardiovascular anomalies through offline diagnosis and/or second opinion (e.g. via internet link).MethodsA retrospective offline analysis of volume datasets of fetuses diagnosed with cardiovascular anomalies by 2D ultrasound was conducted.ResultsThirty-three fetuses with 38 cardiac malformations were evaluated. Mean gestational age at diagnosis was 26 weeks (range, 20–34 weeks). Isolated cardiovascular malformations were detected in 23 fetuses. Extracardiac abnormalities were identified in 8 fetuses, of which 2 had trisomy 21 and 1 had trisomy 18. One fetus exhibited 22q11 microdeletion. Ten pregnancy terminations were performed.ConclusionOffline analysis of cardiovascular anomalies conferred significant diagnostic advantages over 2D ultrasound. 3D ultrasound is invaluable for the prenatal diagnosis and management of congenital heart diseases. It may be used to facilitate scientific cooperation between high- and low-income countries.     

Choroid plexus cysts: Is biochemical testing a valuable adjunct to targeted ultrasonography?

OBJECTIVE: We sought to determine whether biochemical testing is a valuable adjunct to ultrasonography in selecting patients with fetal choroid plexus cysts for amniocentesis. STUDY DESIGN: The study population consists of 128 patients who had fetal choroid plexus cysts detected during ultrasonography performed between 18 and 22 weeks' gestation. The patients had genetic counseling, and amniocentesis and biochemical testing were offered to all patients. The data were analyzed by dividing the patients into 3 groups. Group 1 had targeted ultrasonography only, group 2 had ultrasonography and maternal serum alpha-fetoprotein testing, and group 3 had ultrasonography and triple-screen (maternal serum alpha-fetoprotein, human chorionic gonadotropin, and estriol) testing. Outcome was determined by fetal karyotype or by neonatal examination by a pediatrician for patients who declined amniocentesis. RESULTS: There were 25 patients in group 1. Isolated choroid plexus cysts were detected in 20 fetuses, and all had normal outcomes. Additional anomalies were detected in 5 fetuses. Two had normal karyotypes, and 3 had trisomy 18. There were 52 patients in group 2. The maternal serum alpha-fetoprotein levels were normal in 44 patients, 41 of whom had isolated fetal choroid plexus cysts. Of these 44 patients, 40 had normal outcomes, and 1 patient had a fetus with trisomy 18. The remaining 3 patients with normal maternal serum alpha-fetoprotein levels had additional fetal anomalies on ultrasonography, but the karyotypes were normal. The maternal serum alpha-fetoprotein levels were abnormal in 8 patients, of whom 6 had fetuses with isolated choroid plexus cysts and normal karyotypes. Two patients had additional fetal anomalies detected on ultrasonography and had abnormal karyotypes, 1 with trisomy 21 and 1 with trisomy 18. There were 51 patients in group 3. Results of the triple screen were normal in 32 patients. The choroid plexus cysts were isolated in 29 of the 32 patients, and all 29 fetuses had normal karyotypes. The other 3 patients with normal triple-screen results had additional fetal anomalies on ultrasonography. One fetus had normal chromosomes, and 2 had trisomy 18. The remaining 19 patients had abnormal triple-screen results. Among them, 16 fetuses had isolated choroid plexus cysts, 13 of whom were normal, 2 had trisomy 18, and 2 had a de novo unbalanced translocation. The remaining 3 fetuses had additional anomalies, and all 3 fetuses had trisomy 18. There were 14 fetuses with significant chromosomal abnormalities. Nine mothers were <35 years old, and 5 were >/=35 years old. CONCLUSIONS: This study shows the following: (1) The triple screen is a useful adjunct to targeted ultrasonography in selecting patients with fetal choroid plexus cysts for amniocentesis. (2) A normal triple-screen result and the absence of additional fetal anomalies on ultrasonography reliably exclude an underlying chromosomal abnormality, and amniocentesis is not indicated. (3) If the triple-screen result is abnormal, additional anomalies are seen on ultrasonography, or the mother is aged >/=35 years, then fetal karyotyping is recommended. (4) Patients who decline fetal karyotyping should have follow-up ultrasonography in 34 weeks' time.     

Sonographic detection of fetuses with trisomies 13 and 18: accuracy and limitations

Nine fetuses having trisomy 13 and 15 fetuses with trisomy 18 were diagnosed by cytogenetic studies and also underwent a sonogram between 15 and 40 weeks. All nine fetuses with trisomy 13 had been prospectively identified as having sonographic findings suggestive of trisomy 13. Twelve of the 15 fetuses with trisomy 18 had sonographic abnormalities compatible with trisomy 18. Findings included abnormalities of the face and head, extremities, and diaphragmatic hernia. This report examines criteria for the ultrasound diagnosis of trisomies 13 and 18 and describes the accuracy of prenatal sonography for these diagnoses.     

Sensitivity of prenatal ultrasound for detection of trisomy 18

Objectives: To evaluate the sensitivity of prenatal ultrasound (US) for trisomy (T18) diagnosis and describe US findings in a large tertiary care institution in the USA.

Materials and methods: This was a retrospective cohort of all T18 cases diagnosed at our institution from October 2004 to October 2014 based on prenatal or postnatal genetic diagnostic testing. We included all women with a fetus affected by T18 who had a comprehensive US by a maternal–fetal medicine specialist performed at our institution. US findings were reviewed, classified by organ system, and categorized as an anomaly or soft marker. Chi-square or t-test was used for statistical analysis.

Results: We included 128 cases of T18 with confirmed cytogenetic analysis ?110 (86%) of which were diagnosed prenatally or suspected by cell-free DNA and confirmed postnatally, and 18 of which underwent neonatal blood sampling alone. One hundred and twenty-one (95%) had at least one abnormal US finding. Anomalies were more frequently identified on US at ≥20 weeks as compared with <20 weeks (93% versus 76%; p?=?.004). The mean number of findings detected per fetus was 5.1?±?3.0. Fetuses diagnosed by postnatal sampling alone had a similar number of US exams performed and number of abnormal findings compared to those diagnosed prenatally.

Conclusion: Ninety-five percent of fetuses with T18 had at least one abnormal US finding. This sensitivity of is higher than reported in most prior studies, but is not 100%, and should be considered when counseling women regarding prenatal diagnosis of T18.

Rationale: Historical detection rates for abnormal sonographic findings in trisomy 18 fetuses range from 70% to 100%. These studies are limited by small sample sizes. This is a contemporary study of ultrasound findings in a large group of women with confirmed trisomy 18 by prenatal or postnatal genetic diagnosis. We provide expansive detail on soft markers and anomalies broken down by organ-system and gestational age.