无创DNA检测技术在产前筛查中的临床应用

目的 探讨无创DNA基因检测技术应用于产前筛查中的临床价值及意义。方法 回顾性分析在我院2015年1月~2017年1月针对553例孕妇包括预产期年龄≥35岁的高龄产妇、唐筛结果为高风险、临界风险或单项指标异常、超声软指标等孕妇。在充分知情同意,进行遗传咨询后选择胎儿无创DNA产前检测,对检测结果为高风险孕妇进一步进行染色体核型分析,对低风险孕妇进行电话追踪随访。结果 553例孕妇外周血中,541例低风险,12例高风险,在高风险病例中7例提示21三体异常;2例提示18号染色体异常;1例提示13三体异常;2例提示胎儿性染色体异常;无创DNA检测结果为高风险的12例孕妇,均进行了羊水或脐血穿刺,7例21三体高风险中7例为47,XN,+21;2例18三体高风险者中1例为47,XN,+18,1例为46,XN;1例13三体高风险者中1例为47,XN,+13;2例性染色体异常中,1例为XXY,1例为45X。并对无创DNA检测阴性的出生新生儿进行随访,未诉明显异常。应用无创DNA检测技术诊断胎儿染色体疾病的敏感度为100.00%,特异度为99.91%,假阴性率为0,假阴性率为0.09%,无创DNA产前检测对21三体,13三体和性染色体的符合率为100.00%,对18三体的符合率为50.00%。结论 无创DNA检测技术在产前筛查中准确性高,假阳性和假阴性低的优点,可提高产前筛查效率,减少染色体疾病患儿的出生,是快捷、安全、较介入性产前诊断易于接受、值得推广的安全可靠的产前筛查方法,是今后发展的必然趋势。但无创DNA检测出的高风险孕妇,也必须进行羊水穿刺进一步确诊。     

杭州萧山区7952例孕妇血清产前筛查结果与分娩结局的分析

目的了解孕中期产前筛查对胎儿染色体异常及神经管缺陷的作用,以降低出生缺陷。方法应用时间分辨荧光免疫法对萧山区7952例孕15～19＋6周孕妇血清AFP和Free-β-HCG进行产前筛查,同时对孕妇分娩结局进行随访结果。结果血清产前筛查7952人,高风险222例,高风险率为2.79%。其中21-三体综合征高风险189例;18-三体综合征高风险8例;NTD高风险25例。7952例月孕妇分娩随访结果显示：高风险222例中产前诊断羊水穿刺112例,羊水穿刺率50.45%。其中14人为高风险结局异常,异常发生率为6.30%;通过羊水穿刺检查及超声检查,发现3例21-三体综合征、1例心内膜缺损、染色体缢痕延长1例。低风险7730人中尚有96人为低风险分娩结局异常,占低风险人群的1.24%。以上共计110例结局异常分娩结局病例中,其中31例自然流产、医学终止妊娠41例、死胎19例、新生儿异常19例。结论产前筛查结合产前诊断对预防染色体异常和其他先天畸形儿的出生,具有重要作用。     

孕妇产前诊断指征与胎儿染色体异常的关系

目的探讨产前诊断指征和产前诊断胎儿染色体异常间的关系。方法选择2018年6月至2018年12月于贵港市人民医院就诊的孕妇100例,收集所有孕妇产前诊断指征的资料,同时收集羊膜腔穿刺术检测胎儿染色体核型分析的结果。结果胎儿染色体异常共9例,总异常率占9.00%,其中无创基因检测异常组的胎儿染色体异常检出率为60.00%,明显高于高龄组的3.03%、唐氏筛查高危组的5.26%及胎儿超声异常组的7.69%,差异均有统计学意义(P<0.05);夫妇染色体异常组的胎儿染色体异常检出率为50.00%,明显高于高龄组,差异均有统计学意义(P<0.05);高龄组、唐氏筛查高危组、胎儿超声异常组间异常检出率无明显差异(P>0.05)。结论产前诊断指征与胎儿染色体异常密切相关,羊膜腔穿刺行染色体核型分析,能够有效检出胎儿染色体异常,对于有产前诊断指征的孕妇应尽早接受产前诊断,以降低新生儿出生缺陷的发生率。     

佛山地区产前筛查与产前诊断分析研究

目的佛山地区产前筛查与产前诊断分析研究。方法选择自2006年1月～2008年12月来本院进行产前检查的孕妇共41 656例,其中有2 9101例自愿行血清学筛查,孕周为15～25周,年龄21～42岁,平均年龄为25.73岁。有41 333例行超声筛查,孕周11～36周。对唐氏筛查及B超筛查结果为高风险的孕妇进行遗传咨询,建议进行产前诊断确诊。产前诊断的方法采用羊膜腔穿刺羊水细胞培养或经腹脐静脉穿刺脐血细胞培养,染色体检查采用G带染色。结果在血清筛查2 9101例孕妇中,筛查出高风险3227例,阳性率为11.1%。其中21三体高风险1287例,占4.4%;18三体高风险423例,占1.45%。在血清筛查高风险的3227例孕妇中,接受产前诊断者1065例,占33%（1065/3227）。染色体核型异常者100例,占12.49%,占高风险孕妇的4.12%（100/3227）。其中21三体19例,18三体2例,检出率为1.97%（21/1065）,占染色体核型异常的21%（21/100）。有41 333例行超声筛查,超声检查筛查出高风险851例,阳性率为2.06%。行产前诊断206例,染色体异常45例,占21.84%（45/206）,其中检查出21三体5例,18三体8例,13三体1例,占染色体异常的31.11%（14/45）。结论将孕妇年龄、血清学检测和超声筛查作为产前筛查唐氏综合征的方法,明显提高了筛查阳性率,通过产前筛查将高风险的人群筛查出来作产前诊断,减少了缺陷儿出生。     

怀化地区7859例孕中期唐氏筛查和产前诊断结果分析

目的探讨孕中期唐氏筛查和产前诊断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7859例孕中期(14-20周)妇女进行血清标记物三联方案(hA;FP+free-β-hCG+uE3)检测。筛查结果应用Multical软件计算21三体、18三体综合征和开放性神经管畸形的风险(rish)概率。对于高风险孕妇经遗传咨询,知情同意,自愿选择行产前诊断,于孕18-24周左右在超声引导下进行羊膜腔穿刺,抽取羊水培养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7859例孕妇中,筛查到高风险732例,唐氏筛查阳性率为7.65%(601/7859)。其中367例接受羊水或脐血穿刺产前诊断,占筛查高风险孕妇的50.13%(367/732);发现胎儿染色体异常16例,异常检出率4.36(16/367),其中6例唐氏综合征、5例18-三体综合征、4例Turner’s综合征、1例9号染色体臂间倒位。唐氏筛查高风险和低风险组不良妊娠结局分别为6.15%和1.46%,呈显著性差异(<0.05)。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、提高人口素质有重要临床应用价值。     

母血清、超声及联合筛查对出生缺陷产前诊断的比较性研究

目的探讨母血清生化指标、产前超声及联合筛查对出生缺陷产前诊断的价值。方法回顾性比较研究自2001年1月至2009年12月前行产前检查或遗传咨询的12 221例孕妇,依据其接受产前检查的项目分为血清组、超声组和联合组。筛查后对有介入性产前诊断指征者在超声引导下进行羊水或脐血采集并行染色体分析,确诊是否有染色体异常。结果接受检查的12 221例孕妇中血清组共计6091例,超声组共计5110例,联合组共计1021例。全部孕妇共检出出生缺陷儿937例。其中血清组孕妇中共筛查出高风险孕妇450例,检出染色体异常12例。超声组共检查出胎儿发育异常739例,共检出染色体异常52例。联合组发现胎儿发育异常的孕妇一共有162例,检出染色体异常30例。应用统计学χ2检验进行两两比较,在对染色体异常的检测上,超声的检测率比血清筛查的检测率明显增高（P〈0.05）,而超声与母血清联合筛查的检测率比单纯超声筛查的检测率高（P〈0.05）。结论血清生化指标筛查占用卫生资源较少,方法易掌握,可作为某些染色体病普及性筛查的首选方法;超声筛查为无创性,可重复性高,不受孕周限制,并可检出更多的结构异常;而酌情联合应用血清生化指标筛查和超声筛查,可明显提高染色体异常的检出率,降低筛查假阳性率。     

The effects of ethnicity,education and an informational video on pregnant women's knowledge and decisions about a prenatal diagnostic screening test

Prenatal screening for genetic disease and developmental disabilities is rapidly becoming a routine part of the management of low-risk pregnancies. Yet research on how to best inform pregnant women about these tests and their special ethical entailments remains sparse. We asked 130 low-risk pregnant women of diverse ethnic and social class backgrounds a series of questions about a prenatal test they had been offered within the previous 3 months. All had been given an informational booklet about the test at the time it was offered; about half also saw a video. We found that neither group of women retained much of the information they had received about the prenatal screening but that those who saw the video remembered more. Information-retention also varied significantly by ethnicity and level of education.     

B超引导下脐带及羊膜穿刺术产前诊断294例临床分析

目的：探讨妊娠中期在B超引导下羊膜及脐带穿刺技术在产前诊断中的应用及其手术的安全性。方法：1296例高危孕妇接受遗传优生咨询,294例进行了入侵性操作抽取脐血或羊水进行遗传学及生物化学检测。对其结果,母胎并发症进行分析。结果：阳性标本42份,淘汰病胎37例,羊膜穿刺112例均一次成功,脐带穿刺182例一次成功率98.2%。一针成功率85.3%,全部穿刺未发生严重母胎并发症,结论：正确把握适应症,妊娠中期在B超引导下羊膜穿6刺及脐带穿刺是一种安全有效的产前诊断方法。     

义乌地区24756例孕中期产前筛查及随访结果分析

目的探讨孕中期母血产前筛查在临床中的应用和意义。方法应用时间分辨荧光免疫分析法检测孕中期孕妇血清中甲胎蛋白（AFP）、游离绒毛膜促性腺激素（Free-h CG）、未结合雌三醇（u E3）水平,用专用风险分析软件进行数据计算分析,对筛查出的高风险孕妇经优生遗传咨询,行羊水穿刺和产前超声检查。结果 24 756例孕妇中检出各类高风险人群共1491例,筛查阳性率6.02%;高风险孕妇中羊水穿刺率70.42%,妊娠结局随访率100%,胎儿异常发生率1.81%;低风险孕妇妊娠结局随访率96.05%,胎儿异常发生率0.42%。结论通过孕中期产前筛查和产前诊断,可减少缺陷儿的出生,加强随访能够更好的指导优生工作。     

孕中期唐氏筛查法在高龄孕妇中的意义分析

目的 探究唐氏筛查法在高龄孕妇妊娠中期的检出率及准确性。方法 对2017年1月~2017年10月宜春市妇幼保健院215例进行产前检查的孕妇,运用时间分辨免疫荧光法对血清中的甲胎蛋白、人类绒毛膜性腺激素以及游离雌三醇浓度进行测定。经唐氏筛查法检查后提示唐氏综合征高风险者,进行羊水染色体核型检查,分析比较两组孕妇的唐氏筛查高风险率以及染色体异常率。结果 在200例符合纳入标准的孕妇中,经唐氏筛查共检出高风险孕妇15例,适龄组高风险检出率7例（4.60%）低于高龄组8例（16.67%）,差异有统计学意义（P＜0.05）。高风险孕妇经羊水染色体核型检查后发现唐氏综合征胎儿1例,该例患儿母亲为高龄孕妇,已在18孕周时进行引产。产后随访其他新生儿均未出现上述疾病。高风险胎儿其染色体异常率高于低风险胎儿,差异有统计学意义（P＜0.05）。结论 随着孕妇年龄的增加,唐氏筛查的高风险检出率明显增高,同时经唐氏筛查法提示高风险胎儿其染色体异常率明显高于低风险胎儿,因此妊娠中期应用唐氏筛查法评估异常胎儿情况对高龄孕妇有重要意义。     

甲胎蛋白、人绒毛膜促性腺激素及非结合雌三醇在产前筛查中的临床意义

目的：探讨甲胎蛋白、人绒毛膜促性腺激素及非结合雌三醇在产前筛查中的临床意义。方法：选取我院2014年12月至2015年6月孕周为15~20周的妊娠孕妇血清标本2070例，予以产前甲胎蛋白、人绒毛膜促性腺激素及非结合雌三醇的检测，并且结合孕妇的年龄、孕周、体质量等因素，运用配套的仪器产前筛查风险软件统计唐氏综合症、18–三体综合征及神经管缺陷的风险比例，予以高危孕妇做详细确诊，并依据随访与诊断结果比较高危组与低危组甲胎蛋白、人绒毛膜促性腺激素、非结合雌三醇水平，及出生缺陷阳性确诊率，产前筛查孕妇的年龄分布与出生缺陷的筛查阳性率。结果：高危组甲胎蛋白水平显著高于低危组[(28.74±1.35) vs.(6.93±1.20)μg/L]，人绒毛膜促性腺激素水平显著高于低危组[(2.43±0.37) vs.(1.76±0.25) ng/L]，非结合雌三醇水平明显低于低危组[(5.35±1.23) vs.(7.26±1.14)μg/L]，两组比较差异明显(P<0.05)；≤35岁孕妇出生缺陷总筛查阳性率(4.27%)显著低于>35岁孕妇(26.24%)；高危组孕妇出生缺陷总确诊阳性率(7.14%)明显高于低危孕妇(0.21%)，两组比较差异显著。结论：甲胎蛋白、人绒毛膜促性腺激素及非结合雌三醇产前筛查能够有效筛查出生缺陷的概率，达到优生，值得推广运用。     

The effect of genetic counseling on performance of prenatal cytogenetic diagnosis

Currently the number of pregnant women who have indications for, but do not receive, prenatal cytogenetic diagnosis is increasing. The purpose of this study was to review the prenatal cytogenetic services and to analyze the effect of genetic counseling on performance of the prenatal cytogenetic test. From January 1987 to July 1988, there were 2,796 deliveries at Severance Hospital, Yonsei Medical Center, of which 126 patients had indications for prenatal cytogenetic diagnosis. Chromosomal abnormalities were found in 5 patients (1, monosomy X; 1, trisomy 18; and 3, trisomy 21). Four patients were found in the group who had indications for prenatal cytogenetic diagnosis while only one was found in the group who did not (p less than 0.01). The most common indication for prenatal cytogenetic diagnosis was advanced maternal age (59%). The prenatal test rate was highest in patients whose indications were a previous child with chromosomal abnormality (100%) and parental translocation carrier (100%). Most (89%) of the patients were tested by amniocentesis between the 16th and 20th week of gestation. The two most common reasons for patients not receiving a prenatal cytogenetic diagnosis were late registration (41%) and absence of genetic counseling (34%).     

Psychological response to prenatal genetic counseling and amniocentesis

The purpose of the present study was to characterize the psychological status (attitudes toward selective abortion, perceived risk, comprehension, patient satisfaction, coping, and state anxiety) of pregnant women at increased risk for fetal genetic anomalies who were referred for prenatal genetic counseling and amniocentesis; to determine which of these factors would predict amniocentesis use; and to identify patient outcomes associated with counseling and testing. Participants were 129 women aged 18 years and older who had one or more fetal genetic risk factors. All were recruited from an urban women's health clinic. The results revealed elevated perceptions of risk and moderate state anxiety despite adequate comprehension of, and patient satisfaction with, the process and content of genetic counseling. Approximately 78% agreed to testing; those who consented were more likely to hold favorable attitudes toward abortion than those who refused. Post-counseling, women experienced decrease in their perceived risk of having a baby born with a birth defect although perceived risk estimates remained higher than actual risks. Anxiety was clinically elevated and highest at the pre-counseling stage, though it dissipated to normal levels over time. Previous experience with prenatal diagnostic testing, increased perceived risk of a birth anomaly, and favorable attitudes toward abortion were independently associated with increased pre-counseling anxiety. Women who were more anxious pre-counseling remained more anxious post-counseling. Coping (high versus low monitoring) was unrelated to anxiety. These findings suggest that women who participate in prenatal counseling and testing may be subject to experience distress and unrealistic perceptions of their risk and may benefit from interventions designed to lessen these states.     

Does hygiene counseling have an impact on the rate of CMV primary infection during pregnancy?: Results of a 3-year prospective study in a French hospital

BackgroundCytomegalovirus (CMV) is the most frequent cause of congenital viral infection in developed countries.ObjectivesThe objective of this study was to evaluate the impact of our prenatal CMV infection screening and counseling policy.Study designSince 2005, all pregnant women in our obstetric center have been informed about CMV infection, and if they agree, given a serological test at around 12 weeks of gestation (WG). If this first test is negative, the women and their partners are given hygiene counseling on how to prevent CMV infection, and a second test is performed at around 36 WG.ResultsAmong the 5312 women who had an unknown immune status, or were known to be seronegative when they had their first visit to our center for their current pregnancy, 97.4% agreed to CMV screening. Primary infection was detected in 11 women between 0 and 12 WG (0.42%), and seroconversion was diagnosed in five women between 12 and 36 WG (0.19%).ConclusionsThese results suggest that if clear information is given on CMV infection during pregnancy, the rate of seroconversion is lower following counseling than before counseling.     

2052例羊水细胞产前诊断的染色体结果分析

目的探讨孕中期羊膜腔穿刺产前诊断胎儿染色体异常的经验。方法收集、分析孕中期羊水培养核型分析结果资料。主要的产前诊断指征包括高龄、产前血清学筛查高风险、胎儿超声检查异常等。染色体异常包括常染色体非整倍体,性染色体非整倍体及染色体结构异常。结果成功培养羊水细胞2052例,其中指征为高龄孕妇的占16．0％．血清学筛查阳性占75．0％,胎儿超声检查异常占4．5％,其它原因占4．5％。检出率最高的指征为胎儿超声检查异常。共检出75例染色体异常胎儿,其中非整倍体为51例（68．0％）,染色体结构异常24例（32．0％）。结论本研究证明了羊水细胞用于诊断染色体异常胎儿的作用,其结果可用于临床遗传咨询。     

TCT技术与HPV分型技术在子宫颈病变筛查中的应用价值

为探讨液基薄层细胞检测法（TCT）与人乳头状瘤病毒（HPV）分型检测在子宫颈病变筛查中的应用价值,对18534例妇科宫颈刷检标本进行TCT检测,其中257例标本采用导流杂交技术（FTH）检测HPV分型。结果表明,257例标本中,108例HPV病毒检测结果为阳性（阳性率42.1%）,包括93例高危亚型感染,15例低危亚型感染,20例感染两种以上HPV亚型,149例HPV为阴性（57.9%）。HPV是诱发女性宫颈癌及生殖器病变的主要病源。TCT检测技术联合HPV分型应用于宫颈癌早期防治以及确诊子宫颈病变具有着重要意义。     

产前诊断21三体综合征的临床分析

目的通过对产前诊断中21三体综合征进行临床分析,了解孕龄、唐氏征筛查、家族遗传史及B超异常对21三体综合征发生的影响。方法收集我院2005年至今羊水穿刺产前诊断标本共3960例,其中21三体综合征43例,通过对43例孕妇从发病年龄、家族遗传史、唐氏征筛查及B超异常来综合分析21三体综合征的发生情况。结果 43例21三体综合征中：年龄≥34岁18例,占41.9%;唐筛阳性15例,占34.9%;遗传病史6例,占13.9%;B超异常4例,占9.3%。结论加强对有产前诊断指征孕妇进行必要的产前诊断,可减少21三体综合征患儿的出生;加强宣传,提高孕妇、家庭及社会的对羊水产前诊断的认识。     

A retrospective analysis the clinic data and follow-up of non-invasive prenatal test in detection of fetal chromosomal aneuploidy in more than 40,000 cases in a single prenatal diagnosis center

ObjectiveTo evaluate the efficacy of non-invasive prenatal test (NIPT) in the detection of chromosomal aneuploidy according to the follow-up information from a single prenatal diagnosis center.MethodsA total of 40,311 cases were retrospectively reviewed. The screening was performed using a BGI protocol, pre-test and post-test genetic counseling was provided, and the pregnancy outcomes were recorded. The results of NIPT and clinical follow-up data were analyzed together with the pregnancy outcomes, confirmatory testing results, and ultrasound findings.ResultsOf the 40,311cases were includes in the study, successful follow-up was conducted in 468 (1.16%) cases with high risk, 225 (0.56%) cases with rare autosomal trisomy (RAT) and copy number variation (CNV). 39,572 (98.17%) cases with low risk and 623 (1.57%) cases of which were confirmed with adverse pregnancy outcomes. 46 (0.1%) cases with failed tests. Among them, 398 (84.7%) cases with high-risk results chose invasive testing, revealing 198 true positive cases. In cases with RAT and CNV results, 189 cases underwent invasive testing, revealing 5 cases RAT and 4 pathogenic CNVs.ConclusionsNIPT appears to be effective in detecting the fetal chromosomal aneuploidies T21, T18 and SCAs, but it exist false positive/negative cases, unconfirmed high-risk cfDNA results, and the high false positive rate in cases with RAT and CNV results implied the limitations of this screening method. Our study showed the importance to associate cfDNA screening results with clinical follow-up data and provided information that may help with result interpretation, genetic counseling and the decision making in clinic.     

Predictors of failure to return for HIV test results among pregnant women in Moshi, Tanzania

Identification of HIV-infected women is a prerequisite in HIV perinatal prevention programs. The aim of this study was to determine the predictors of failure to return for HIV posttest results among pregnant women (N=2654) receiving antenatal care at primary health clinics in Moshi urban district, Tanzania. Consenting pregnant women, who were in the third trimester of pregnancy, received individual pretest counseling, followed by interview and screening for HIV. Posttest counseling and results were given after 1 week. A total of 182 (7%) failed to return for their HIV test results. Women were less likely to return for test results if their partners did not come for testing (adjusted odds ratio [AOR], 12.6; 95% CI, 3.1-51.4), if their partners consumed alcohol (AOR, 1.8; 95% CI, 1.3-2.7), and if they had never discussed reproductive health matters with their partners (AOR, 1.7; 95% CI, 1.1-2.7). Additionally, the site of recruitment, age, alcohol consumption, and advanced gestation age predicted failure to return for HIV test results. These results indicate that male partner factors were important in determining whether women returned for results. We therefore recommend promotion of antenatal couple counseling and strengthening of community awareness of the availability of perinatal interventions, with special efforts targeting men. Furthermore, the predictors for failure to collect test-results need to be addressed during pretest counseling.     

Prenatal diagnosis of neural tube defects: predictive value of AF-AFP in a low-risk population

Amniotic fluid alpha-fetoprotein (AF-AFP) determinations were performed on 1,215 women who were at low risk for fetal neural tube defects and who were undergoing mid-trimester amniocentesis for cytogenetic indications, primarily age-related aneuploidy. Maternal sera obtained before amniocentesis and amniotic fluids were assayed in duplicate for alpha-fetoprotein by radioimmunoassay. Of the 1,215 low-risk women, eight (0.7%) had significant elevations of AF-AFP (greater than or equal to +5 SD). In none of the cases was the elevation associated with a fetal neural tube defect. Two cases with elevated AF-AFP were associated with chromosome aberrations; one with impending fetal demise; one with fetal blood contamination; and one case was due to a laboratory error. In one case, no source for the elevated AFP was found, and a normal infant was delivered at term. In the final two cases, the cause of the elevated AF-AFP was a fetal abdominal wall defect (one gastroschisis and one omphalocele). The predictive value of an elevated AFP varies with the population screened, and is reduced by routine ultrasonography before amniocentesis, which at least identifies anencephaly. In a low-risk population, an elevated AF-AFP is most often not associated with a fetal neural tube defect. Because of the low predictive value and the nonspecificity of AF-AFP, genetic counselors should reconsider the recommendation of routine AF-AFP in low-risk maternal populations.