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。     

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。     

孕妇血清妊娠相关血浆蛋白A水平与不良妊娠的关系

目的 :确定不同孕周的孕妇其妊娠相关血浆蛋白A(PAPP A)的正常参考值 ,分析PAPP A水平与不良妊娠的关系。方法 :用酶联免疫吸附试验 (ELISA)测定孕妇血清PAPP A浓度 ,统计各孕周孕妇PAPP A值 ,并分组讨论不良妊娠与PAPP A的关系。结果 :获得 4～ 4 2周PAPP A浓度中位数、0 5倍中位数、2 5倍中位数。PAPP A低值与胎儿核型异常、难免流产、死胎有关 ;PAPP A高值与双胎、中重度妊高征有关 ;先兆流产预后差者PAPP A值低于先兆流产预后佳者。结论 :从 14 0 0例孕妇血清中得到的PAPP A浓度统计值 0 5～ 2 5MoM可作为正常参考 ,试用于我省产前筛查 ;母体血清PAPP A的测定值可作为胎儿染色体异常、流产、死胎、妊高征及双胎的辅助诊断指标。     

荧光原位杂交技术在妊娠晚期应用价值探讨

目的:探讨妊娠晚期宫内发育异常胎儿羊水间期细胞荧光原位杂交(FISH)检测的意义。方法:选取2014年1月至2015年12月青岛市妇女儿童医院胎儿医学中心接诊的妊娠26~40周行羊水细胞FISH检测的83例孕妇。评价妊娠晚期FISH技术用于检测唐氏筛查高风险孕妇、高龄孕妇以及发育异常胎儿染色体异常检测的意义。结果:80例孕妇接受妊娠晚期羊水细胞FISH检测,有妊娠中期产前诊断指征的孕妇中,胎儿染色体异常患病率为26%(8/31)。妊娠晚期发现发育或结构异常的胎儿中,胎儿染色体异常患病率为6%(3/49)。妊娠晚期出现发育或结构异常的胎儿中,3例患儿均为21三体,其妊娠晚期超声表现分别为侧脑室扩张合并脐血流异常、十二指肠闭锁合并羊水扩张及胎儿生长受限。结论:对于妊娠中期有产前诊断指征但错过诊断时机的胎儿,需在妊娠晚期行羊水细胞FISH检测。妊娠晚期超声提示发育或结构异常的胎儿,需考虑行羊水FISH检测。     

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。     

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。     

孕妇血清PAPP-A与妊高征的相关性研究

目的:探讨孕妇血清妊娠相关血浆蛋白A(PAPP A)与妊娠高血压综合征(妊高征)之间的相关性。方法:采用双抗夹心酶联免疫法测定1 0 3例正常孕妇及95例妊高征患者血清PAPP-A的水平。结果:①正常妊娠随着孕周的延长,PAPP -A水平呈稳定的增高趋势。孕周与PAPP A呈正相关。②妊高征组的PAPP A水平明显高于对照组,组间差异有非常显著性(P <0 .0 1 ) ,而且随着病情的加重,PAPP A水平呈增高趋势,组间差异有非常显著性(P <0 .0 1 )。③不同妊娠时期,妊高征组的PAPP A水平均显著高于对照组的相应时段,组间差异均有非常显著性(P <0 .0 1 )。结论:孕妇血清PAPP A水平可作为诊断妊高征的客观指标及判断病情严重程度的参照指标。     

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。     

荧光原位杂交技术在检测假性肥大型肌营养不良症缺失型携带者中的应用

目的:应用荧光原位杂交(FISH)筛查技术检测假性肥大型肌营养不良症(DMD/BMD)缺失型携带者。方法:以外显子特异Cosmid DNA为探针(含18个外显子),采用中期和间期单色FISH技术,对9例正常男、女性及来自不同缺失型DMD/BMD家系的5例女性外周血标本、来自健康孕妇的2例羊水和2例绒毛标本进行分析。结果:72～100％外周血淋巴细胞中期相或间期核、60～70％羊水细胞间期核、95～99％绒毛细胞间期核显示预期信号。FISH检出1名、排除2名缺失型携带者。结论:充分利用FISH技术优点,结合现有其它技术,可有效筛查DMD/BMD缺失型携带者,并为女性胎儿DMD/BMD缺失型携带者产前诊断奠定基础。     

早期正常和异常妊娠相关血浆蛋白-A水平研究及意义

目的：探讨妊娠相关血浆蛋白－A（PAPP－A）与先兆流产，异位妊娠、葡萄胎等异常妊娠的相关性及临床意义。方法：采用ELISA双抗夹心酶联免疫法对100例5－12周正常妊娠PAPP－A的亚单位SPP－A水平进行测定，确定SPP－A医学参考值范围。测定35例先兆流产、23例异常妊娠6例葡萄胎SPP－A值并与同孕周正常妊娠SPP－1值进行比较，结果：早期正常妊娠PAPP－A自第5孕周始随孕周而逐渐升高，先兆流产和异位妊娠的PAPP－A明显低于同孕周正常妊娠均值，差异显著，经保胎治疗的无兆流产PAPP－A低值者，仍有63．6％发生流产；95．7％异位妊娠患者PAPP－A分布在同孕周正常妊娠中位数值以下；葡萄胎患者PAPP－A较同孕周正常妊娠中位数值高。结论：PAPP－A可作为早孕诊断指标。在先兆流产，异位妊娠及葡萄胎的早期诊断，判断预后及监测等方面具有重要的临床价值。     

21-三体综合征妊娠早期联合筛查模式的评估

目的：评估妊娠早期联合筛查21-三体综合征模式的质量。方法：入选者为500例妊娠11～13＋6周进行产前筛查的妊娠妇女,超声检测胎儿颈项透明层（nuchal translucency,NT）厚度,同时取妊娠妇女静脉血,以时间分辨法检测血清中游离人绒毛膜促性腺激素亚单位（β-hCG）及妊娠相关蛋白A（PAPP-A）水平,并根据患者年龄、体质量、种族、吸烟史、妊娠方式、妊娠周数等转化成该指标的中位数倍数（MoM）,风险值为1∶270,联合评估妊娠妇女21-三体综合征的患病风险,记录实施产前诊断妊娠妇女胎儿的染色体核型。所有妊娠妇女均进行妊娠期监测及产后随访,将妊娠妇女及胎儿结局输入数据库。最后对妊娠早期时的筛查模式及筛查质量进行评估。结果：①500例中有6例为21-三体高风险（行产前诊断5例）,其中3例在产前诊断时确诊。另有40例为年龄高风险（＞35岁）,其中5例行产前诊断,均为正常核型胎儿。②在妊娠早期,非21-三体核型胎儿的NT厚度随其顶臀长（CRL）增加而增加。③正常胎儿母亲血清PAPP-A水平随妊娠周增加而增加,β-hCG水平随妊娠周增加而下降。结论：①单独年龄高风险不应作为产前诊断的指标。②NT厚度与妊娠周相关,应进行多中心大样本研究,并根据不同妊娠周建立适合中国人群的NT诊断标准。③妊娠早期筛查应在有超声NT测量资质的医院进行,且最好在妊娠12周时进行。④妊娠早期母亲血清PAPP-A及β-hCG水平变化与妊娠周有关。     

应用荧光原位杂交技术快速诊断胎儿染色体数目异常

目的 探讨荧光原位杂交（ｆｌｕｏｒｅｃｅｎｔ ｉｎ ｓｉｔｕ ｈｙｂｒｉｄｉｚａｔｉｏｎ,ＦＩＳＨ）技术在快速产前诊断胎儿染色体数目异常中的价值。方法 对２０例孕１６￣３６周,有产前诊断指征者,在Ｂ超引导下经腹抽取羊水后,应用Ｘ、Ｙ、１８号染色体着丝粒探针１３ｑ１４－ｑ２１和２１ｑ１１特异性探讨,对未培养的羊水间期细胞进行ＦＩＳＨ,然后用荧光显微镜进行观察,并用Ａｐｐｌｉｅｄ ｉｍａｇｉｎｇ染色体     

Prenatal diagnosis and prevalence of Down syndrome in the Parisian population, 2001-2005

OBJECTIVES: To assess recent trends in the prevalence of Down syndrome and the proportion of cases with a prenatal diagnosis in the Parisian population. PATIENTS AND METHODS: Four hundred and ninety-nine cases of Down syndrome were registered by the Paris Registry of Congenital Anomalies during the period 2001-2005. All cases with prenatal diagnosis were confirmed by cytogenetic examination. We analyzed trends in the total and live birth prevalence, the proportion of cases with a prenatal diagnosis and those with a pregnancy termination, as well as gestational age at diagnosis and termination. Analyses were stratified by maternal age and trends were tested by the Cochran-Armitage test and Anova. RESULTS: Total prevalence of Down syndrome remained high (37.6 per 10,000 births, 95%CI 34.2-40.9) during this period because of advanced maternal age in Paris. The proportion of cases with a prenatal diagnosis (overall average 85.5%, 95% CI 81.8-88.1), and live birth prevalence of Down syndrome (7.1 per 10,000 live births, 95%CI 5.7-8.6) have remained fairly stable over time. The great majority of women (95% CI 95% 92.7-96.9) opted for a pregnancy termination following a prenatal diagnosis of Down syndrome. A trend towards an earlier gestational age at prenatal diagnosis was noted among women less than 30 years of age. DISCUSSION AND CONCLUSION: It is important to continue to evaluate changes in the prenatal diagnosis of Down syndrome, notably in view of potential changes in screening practices and policies, and particularly if a first trimester strategy is adopted following recent recommendation by the "Haute Autorité de santé".     

经母血采集胎儿细胞行产前诊断的最佳时间探讨

目的：探讨利用母血循环中胎儿细胞进行产前诊断的最佳采血时间。方法：对４１例孕龄为６～１４周的妇女连续取血，采用套式聚合酶链反应技术检测人类Ｙ染色体特异的锌指蛋白基因（ＺＦＹ）。结果：１９例妊娠男性胎儿妇女外周血ＺＦＹ随着孕龄的增加，其胎儿单拷贝基因的检出率增高，其中孕６周时检出率为１／１９（５．３％），孕１１周时为１３／１９（６８．４％），而到孕１４周时，则达到１８／１９（９５．０％）；对２２例妊娠女性胎儿妇女外周血进行ＺＦＹ检测时，无一例假阳性结果，这一检测方法在妊娠早期进行胎儿性别鉴定的总准确率达到９７．８％（４０／４１）。结论：利用母血循环中胎儿细胞进行产前诊断的最佳采血时间应在妊娠１４周，同时提示胎儿细胞最早进入母血循环中的时间在不同个体间存在明显的差异。     

采母体外周血应用PCR技术产前检测胎儿性别初探

建立一种对性连锁遗传病胎儿进行非侵入性产前诊断的快速,实用的方法。方法用套式聚合酶链反应技术对１８例孕周为１８－４０周,年龄为２２－３０岁的初产妇外周血男性单拷贝的ＤＹＳ１４基因进行特异性扩增。     

Nuchal Translucency Thresholds in Prenatal Screening for Down Syndrome and Trisomy 18

ObjectiveTo determine if nuchal translucency (NT) can be used as a first trimester triage marker in prenatal screening for Down syndrome and trisomy 18.MethodsData from first trimester prenatal screening in 77 443 women were stratified by maternal and gestational ages. They were then analyzed to identify NT thresholds above or below which only positive (high-risk) or negative (low-risk) results were reported by a first trimester prenatal screening test combining PAPP-A, free β-hCG and NT.ResultsCombined prenatal screening was always positive for Down syndrome when NT thickness exceeded 4.0 mm. As women aged, this upper NT threshold value changed according to gestational age. In women aged 35 to 37 years, combined prenatal screening was always positive when NT exceeded 2.8 mm, 3.0 mm, and 3.4 mm at 11, 12, and 13 weeks of gestation, respectively. In women over 42 years of age, the upper threshold value for NT was 1.8 mm, 2.4 mm, and 2.7 mm at 11, 12, and 13 weeks of gestation, respectively. In women less than 35 years of age, we identified lower threshold values below which combined prenatal screening for Down syndrome was always negative.ConclusionIn prenatal screening for Down syndrome and trisomy 18, it is possible to identify NT threshold values above which biochemical screening provides no additional benefit. In pregnancies in which NT is above the established upper cut-offs, invasive prenatal screening can be offered without delay.     

Preference assessment of prenatal diagnosis for Down syndrome: is 35 years a rational cutoff?

OBJECTIVE: To compare the perceptions of miscarriage and birth of a child with Down syndrome among pregnant women and to evaluate the implications of these preferences for the traditional 35-year old maternal age risk boundary. METHODS: An interviewer-administered survey was given to 186 pregnant women receiving antepartum care at a university hospital. Preferences, as reflected by utilities, for birth of a child with Down syndrome and pregnancy miscarriage, stratified by patient characteristics, were assessed. RESULTS: The utility for the birth of a child with Down syndrome decreased (p < 0.001) as clinical severity increased from mild (0.78) to severe (0.65). Miscarriage of a pregnancy had a mean utility of 0.76 +/- 0.31. Women who desired prenatal diagnosis had a utility value for miscarriage (0.79 +/- 0.28) that was significantly higher than for the birth of a child with Down syndrome of unknown severity (0.73 +/- 0.27). In multivariable logistic regression, desire for prenatal diagnosis was the only factor associated with a preference of miscarriage over birth of an affected child (odds ratio 2.26, 95% confidence interval 1.03, 4.96). CONCLUSION: Women who desire prenatal diagnosis do not perceive the birth of a child with Down syndrome and a pregnancy miscarriage to be equivalent health states. This finding calls into question the rationale of the 35-year-old maternal age criterion and suggests that actual patient preferences should be better incorporated into the decision to offer definitive prenatal diagnosis.     

Periconceptional exposure to contraceptive pills and risk for Down syndrome.

OBJECTIVE: There are some studies which analyzed the relationship between prenatal exposure to oral contraceptives (OCs) and Down syndrome, with conflicting results even in women using OCs and conceiving at different intervals after discontinuing the use of contraceptive pills. We analyzed the risk for Down syndrome in infants of women who become pregnant while taking OC. STUDY DESIGN: We used the data from the Spanish Collaborative Study of Congenital Malformations (ECEMC). The ECEMC is a case-control study and surveillance system. For each malformed infant (case), the next non-malformed infant of the same sex born in the same hospital is selected as a control subject, from whom the collaborating physicians collected the same data as for the malformed infant. For the present study, we used two different approaches. First, the pair-matching analysis. Second, a case-control using the rest of the total of 17,183 controls from the ECEMC database with specified data on maternal use of OCs and maternal age. To control for maternal age, we used a logistic regression analysis. RESULTS: The results show an increased risk of 2.8-fold for infants with Down syndrome in women younger than 35 years of age if the mother became pregnant while she was taking OCs. We did not observe this result for women older than 34 years of age. CONCLUSION: Our results showed that the risk for Down syndrome in infants born to mothers with less than 35 years of age (as a group) who became pregnant while taking OCs is near the risk for Down syndrome of mothers with more than 34 years of age, women who are candidates for prenatal diagnosis. Thus, based on our results, one may consider the possibility of offering prenatal diagnosis for Down syndrome to young women who became pregnant while taking OCs.     

妊娠中期二联唐氏综合征筛查法在浙南地区32188例孕妇中的筛查效率

目的 采用二联法(母血清甲胎蛋白和β-人绒毛膜促性腺激素)对浙南地区妊娠中期孕妇进行唐氏综合征筛查,评估其筛查效率. 方法 对本地区孕妇根据知情同意原则在妊娠中期取羊水进行常规二联唐氏综合征筛查,筛查出的高风险(≥1∶270)孕妇采用羊膜腔穿刺、羊水细胞培养和染色体核型分析进行产前诊断.通过本地区的三级妇幼保健网对本地区行产前唐氏综合征筛查或未行筛查的孕母分娩的新生儿进行临床随访,对可疑唐氏综合征的新生儿行外周血染色体核型分析进行诊断.正态分布计量资料采用均数±标准差(x-±s)表示,组间差异比较采用两独立样本t检验；计数资料用率表示,组间差异比较采用x2检验.唐氏综合征的危险概率用随机筛查软件进行统计分析. 结果 2007年10月至2010年5月,本地区共32 188例单胎妊娠孕妇接受筛查,唐氏综合征高风险者为1130例,低风险31 058例.高风险者中90.79％(1026/1130)接受产前诊断,确诊7例唐氏综合征胎儿均引产终止妊娠；另外104例未接受产前诊断的孕妇分娩1例唐氏综合征患儿.31 058例低风险者中新生儿出生后确诊唐氏综合征6例,发生率0.19‰.接受产前筛查者中唐氏综合征患病率为0.43‰(14/32 188).妊娠中期二联唐氏综合征筛查检出率为57.14％(8/14),假阳性率为3.48％(1122/32 188),阳性预测值为7.08‰(8/1130).同期,由于各种原因未接受唐氏综合征产前筛查的孕妇达到23 813例,分娩唐氏综合征患儿15例,患病率0.63‰.与接受筛查者中的患病率(0.43‰)差异无统计学意义(x2=1.004,P＞0.05).本地区唐氏综合征总体患病率为0.52‰(29/56 001). 结论 产前筛查和诊断可以减少唐氏综合征患儿出生.但本研究中妊娠中期二联唐氏综合征筛查法的检出率、假阳性率和阳性预测值均较低,可能与本研究所采用的正常值范围并不适用于中国人群有关.     

Diagnosis of fetal acrania during the first trimester nuchal translucency screening for Down syndrome.

OBJECTIVES: Prenatal screening during the first-trimester using fetal nuchal translucency (NT) measurement and maternal serum levels of free beta-human chorionic gonadotropin (hCG) and pregnancy-associated plasma protein-A (PAPP-A) has become an established method for the detection of fetal Down syndrome. Increasing evidence has shown that some of the fetal structural abnormalities could be identified during NT scanning. Second trimester maternal serum alpha-fetoprotein (MSAFP) measurements and ultrasound scans have been widely used in clinical practice to identify fetal neural tube defects (NTDs). In this study, we evaluated the effectiveness of early diagnosis of fetal acrania during NT scanning. METHODS: We reviewed the medical records of 5890 pregnancies that were delivered in our hospital between January 1, 1999 and January 31, 2001. Among them, 3600 pregnant women received NT-based Down syndrome screening at 10-13 weeks' gestation. Pregnancies with fetal NTDs were evaluated and their maternal serum levels of free beta-hCG and PAPP-A were compared with those of the normal control pregnancies. RESULTS: Seven of the 3600 pregnancies were identified with fetal acrania and all of them were detected during first-trimester NT scanning. Among the seven cases, five had measurements of maternal serum concentration free beta-hCG and PAPP-A concentration, yet there were not significant difference between the pregnancies with fetal acrania and those of the control pregnancies (PAPP-A, 1.13 vs. 0.96; free beta-hCG, 1.10 vs. 1.06; P>0.05). Two of the seven affected patients did not have maternal serum biochemical measurements due to the immediate termination of pregnancies. CONCLUSIONS: We demonstrated that pregnancies with fetal acrania could be easily identified at the time of NT scanning. Careful ultrasound inspection of fetal structure during NT measurements at 10-13 weeks of gestation provides an encouraging advantage for early diagnosis of fetal acrania.