孕中期唐氏筛查假阳性在预测胎膜早破中的临床意义

目的探讨孕中期唐氏筛查假阳性在预测胎膜早破中的临床意义。方法我院2009年1月至2013年7月有321例妊娠中期唐氏筛查高风险孕妇,均行染色体检查排除染色体异常,孕期序列超声检查未见胎儿器官结构异常,电话或者门诊随访妊娠结局;同时随访346例低风险孕妇妊娠结局,孕期超声亦未发现器官结构异常。结果 321例孕妇唐氏筛查假阳性孕妇中,14例因胎膜早破流产(孕龄小于28周);17例因胎膜早破早产,其中孕28周至孕34周为9例,孕34周至孕37周为8例;新生儿窒息为7例。低风险组中,孕28周前因胎膜早破发生流产6例,3例孕28周至孕34周之间因胎膜早破发生流产,4例孕34周至孕37周发生胎膜早破,新生儿窒息为3例。结论唐氏筛查假阳性孕妇相对于低风险孕妇,更容易发生胎膜早破;唐氏筛查高风险可作为预测胎膜早破的一个潜在指标。     

攀枝花地区2009～2011年孕中期产前筛查结果分析

目的分析攀枝花市2年半的产前筛查/产前诊断情况。方法对6907例孕15～20+6w单胎妇女进行血清甲胎蛋白(AFP)和游离绒毛膜促性腺激素(β-hCG)二联标志物的筛查,对高风险孕妇进行遗传咨询,在知情同意的情况下选择羊水染色体检查以明确诊断。结果 6907例经产前筛查有288例为高风险,筛查阳性率达4.17%;253例染色体高风险孕妇,经知情同意有159例进行羊水产前诊断,诊断率62.84%;确诊胎儿染色体异常2例,其中唐氏综合征1例、18-三体1例。经随访共发现不良妊娠结局29例,其中唐氏综合征新生儿1例;2年半内共发生3例假阴性,假阴性率达0.45‰。结论妊娠中期产前筛查/产前诊断是防止出生缺陷、提高出生人口素质的有效手段。     

5694例单胎中孕期唐氏征血清学筛查效果分析

目的探讨孕中期唐氏征血清学筛查在检出胎儿21-三体综合征的临床应用价值,对本实验室中期唐氏征血清学筛查进行效果分析。方法采15-20^＋6孕妇静脉血进行唐氏中期三联筛查,高风险结果无创产前筛查或直接产前诊断,电话随访妊娠结局。结果唐氏征血清学筛查共检出2卜三体高风险病例379例,羊水细胞染色体核型分析共确诊胎儿21-三体综合征7例,18-三体综合征3例,13-三体综合征1例,嵌合体1例,其他染色体结构异常3例。随访结果唐氏征筛查高风险病例中,B超胎儿畸形的发生率明显高于低风险人群。结论中孕期唐氏征血清学筛查在检出胎儿21-三体综合征和B超结构异常病例中具有临床应用价值,本实验室21-三体筛查假阳性率6．5％（371／5686）,检出率62．5％（5／8）。     

深圳地区44147例唐氏筛查临床分析

目的探讨早孕期和中孕期唐氏筛查对检出胎儿染色体异常的临床价值。方法 2008年1月至2010年12月,应用时间分辨荧光免疫法分别对11 328例早孕期（8～13＋6周）妇女和32 819例中孕期（14～20＋6周）妇女进行唐氏综合征的血清标记物检测。对于唐氏筛查高风险的孕妇,于孕16～22w进行羊膜腔穿刺,抽取羊水进行胎儿染色体核型分析。结果 11 328例早孕期妇女,627例唐氏筛查高风险;其中21-三体高风险596例,18-三体高风险31例。32 819例中孕期妇女,2072例唐氏筛查高风险;其中21-三体高风险1898例,18-三体高风险56例,神经管缺陷（NTD）高风险118例。其中,842例接受羊水穿刺（其中,早孕期高风险210例,中孕期高风险632例）,发现胎儿染色体异常39例（早期15例,中期24例）,异常检出率为4.63%。其中,羊水穿刺确诊18例唐氏综合征。4例18三体综合征。1例Turner＇s综合征1例47,XXX 9例9号染色体臂间倒位、其他6例。结论孕期唐氏筛查是预测胎儿染色体异常的有效指标。结合羊水培养,对预防先天缺陷儿出生有重要临床应用价值。     

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。     

江苏地区以人群为基础的唐氏综合征产前筛查和诊断研究

目的 对江苏省中期妊娠孕妇的胎儿进行唐氏综合征筛查和诊断,减少21三体综合征患儿出生.方法 用分层和整群抽样相结合的多阶段抽样方法,对江苏省怀孕15～20周的26 803名妇女采用时间荧光分辨法进行母血清常规二联筛查,筛查出的高风险孕妇进行羊膜腔穿刺、细胞培养、染色体分析.出生儿童通过面访和外周血染色体培养确诊.结果 血清筛查和羊水染色体检查,确诊6例胎儿;出生儿童随访和外周血染色体分析确诊3例,共确诊9例唐氏综合征,产前筛查检出率为67%(6/9).结论 产前筛查和诊断可以减少唐氏综合征患儿出生,提高出生人口素质.但是应提高产前筛查的准确性,最大限度地降低假阴性,减少或杜绝漏诊发生.     

孕中期血清唐氏综合征筛查与不良妊娠结局关联

目的 研究孕中期唐氏综合征筛查与不良妊娠结局关联及甲胎蛋白(AFP)、β人绒毛膜促性腺激素(β-HCG)、游离雌三醇(uE3)单个指标与不良妊娠发生的关联。方法 采用连续性入组方法选取2014年3月31日至2021年4月29日在北京朝阳医院进行唐氏综合征筛查的孕妇进行回顾性队列研究。结果 在7 682例孕妇中,筛查高风险者492例,占6.40%;共有100例孕妇出现了不良妊娠结局(1.30%)。筛查高风险孕妇中有21例发生不良妊娠结局,发生率为4.27%,显著高于筛查低风险者(1.10%)。调整了糖尿病史、遗传病家族史、吸烟、饮酒后,与低风险值相比,筛查高风险者发生不良妊娠结局的可能性高达4.022倍(95%CI:2.405-6.442);21三体风险值越高,不良妊娠结局的发生率越高(P<0.001)。筛查高风险组在胎儿畸形、染色体异常、胎停育的发生率显著高于低风险组(P<0.05)。AFP原始数值每升高1 ng/mL,发生不良妊娠结局的可能性上升到1.019倍;AFP中位数倍数值(MOM)每升高1,发生不良妊娠结局的可能性上升2.258倍;uE3原始数值每升高1 ng/m...     

孕中期血清唐氏综合征筛查与不良妊娠结局关联

目的 研究孕中期唐氏综合征筛查与不良妊娠结局关联及甲胎蛋白(AFP)、β人绒毛膜促性腺激素(β-HCG)、游离雌三醇(uE3)单个指标与不良妊娠发生的关联。方法 采用连续性入组方法选取2014年3月31日至2021年4月29日在北京朝阳医院进行唐氏综合征筛查的孕妇进行回顾性队列研究。结果 在7 682例孕妇中，筛查高风险者492例，占6.40%;共有100例孕妇出现了不良妊娠结局(1.30%)。筛查高风险孕妇中有21例发生不良妊娠结局，发生率为4.27%,显著高于筛查低风险者(1.10%)。调整了糖尿病史、遗传病家族史、吸烟、饮酒后，与低风险值相比，筛查高风险者发生不良妊娠结局的可能性高达4.022倍(95%CI:2.405-6.442);21三体风险值越高，不良妊娠结局的发生率越高(P<0.001)。筛查高风险组在胎儿畸形、染色体异常、胎停育的发生率显著高于低风险组(P<0.05)。AFP原始数值每升高1 ng/mL,发生不良妊娠结局的可能性上升到1.019倍；AFP中位数倍数值(MOM)每升高1,发生不良妊娠结局的可能性上升2.258倍；uE3原始数值每升高1 ng/m...     

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。     

2008年衢州地区联合血清学和超声进行产前筛查分析

目的探讨孕中期孕妇血清标志物甲胎蛋白（AFP）和游离人绒毛促性腺激素B亚单位（Free-βhCG）检测及超声在产前筛查中的作用。方法应用时间分辨荧光免疫分析系统对妊娠15～20周的10242例孕妇进行血清AFP和Free-βhCG的检测及分析,风险率≥1：270为唐氏综合征,神经管畸形（NTD）筛查高风险;风险率≥1：350为18三体综合征筛查高风险,经产前诊断及超声、新生儿检查得以确认。结果10242例筛查孕妇中,唐氏综合征筛查高风险296例。检出4例21三体,2例染色体多态;18三体高风险65例,检出1例18三体;神经管畸形（NTD）高风险62例,检出NTD10例。高风险者中染色体异常和各脏器畸形儿检出19例,检出率4．49％。在唐氏综合征筛查低风险孕妇9163例中发现11例胎儿畸形（阳性发现率1．20‰）,漏诊1例21三体。结论孕中期孕妇血清生化筛查和超声筛查胎儿唐氏综合征有效的产前筛查方法,高风险孕妇中阳性诊断率要高出低风险孕妇阳性检出率37．4倍,可见联合产前筛查明显提高染色体异常和畸形儿阳性检出率。     

Maternal transmission of translocation 2;21 associated with Down''s syndrome.

An unusual 2;21 translocation associated with Down's syndrome is reported. The proband was a 3 year old boy, clinically diagnosed as having Down's syndrome and with a family history of Down's syndrome. Maternal age at the time of study was 28 years. Out of the four sibs with Down's syndrome three had died. Two pregnancies ended in first trimester miscarriage. The proband was found to have trisomy 21 associated with a 2;21 translocation inherited from his mother.     

Triple marker screening for fetal chromosomal abnormalities in Korean women of advanced maternal age

The purpose of this article is to assess the value of maternal serum triple marker screening of alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG), and unconjugated estriol (uE3) for the prenatal diagnosis of fetal chromosomal abnormalities in Korean women of advanced maternal age. Maternal sera were collected from 458 pregnant Korean women aged 35 between 15 and 20 weeks gestation before amniocentesis. A patient- specific second trimester risk for fetal Down's syndrome was calculated using the median values for AFP, hCG, uE3 and maternal age. Twelve fetal chromosomal abnormalities were identified. These included six cases of trisomy 21, one case of 46,XY/47,XY,+21, two cases of trisomy 18, one case of trisomy 13, and two cases of 45, X. A cutoff level of 1:200 detected 85.7% (6/7) of the cases of Down's syndrome and 20% (1/5) of the other aneuploidies, with a 27.3% false positive rate. However, a cutoff level of 1:270 did not result in any gains in detecting Down's syndrome or other aneuploidies at the expense of a false positive rate of 34.3%. Second trimester triple marker testing is an effective screening tool for detecting fetal Down's syndrome in Korean women > or = 35 years old. However, it is not an effective screening tool for non-Down's chromosomal abnormalities.     

Second-trimester maternal urine human chorionic gonadotrophin beta-core fragment concentrations in Asian pregnancies with fetal chromosomal abnormalities.

The aim of this study was to investigate the second trimester concentrations of maternal urine human chorionic gonadotrophin beta-core fragment (HCGbetacf) in Asian pregnanci2es with fetal chromosomal abnormalities. HCGbetacf concentrations were analysed from 34 urine samples in chromosomally abnormal pregnancies, including 28 cases of Down's syndrome, one case of trisomy 18, and five cases of other chromosomal abnormalities (one mosaic deletion and four translocations), and in a cohort of 268 normal pregnancies receiving second trimester amniocentesis. Results were normalized to urine creatinine (Cr) concentration and converted to the multiple of the median (MOM) concentration for the appropriate gestation. The median HCGbetacf MOM concentrations of Down's syndrome pregnancies (12.89) was significantly higher than that of normal pregnancies (1. 06) (P < 0.00001). Wide variations of HCGbetacf concentrations were observed in other chromosomally abnormal pregnancies. There were 18 of 28 (64%) Down's syndrome cases but one of five (20%) other chromosomally abnormal cases with HCGbetacf concentrations above the 95th centile of the control values (8.22 MOM cut-off). These findings suggest that HCGbetacf could be a potential marker in urine screening for fetal Down's syndrome in Asians.     

Prenatal screening for Down's syndrome with use of maternal serum markers.

BACKGROUND. Approximately 35 percent of all cases of Down's syndrome in fetuses can be detected by measuring maternal serum alpha-fetoprotein during the second trimester in the general population of pregnant women. Recent case-control studies indicate that this detection rate could be approximately doubled by measuring serum levels of unconjugated estriol and chorionic gonadotropin, which are abnormally low and abnormally high, respectively, in women carrying fetuses affected by Down's syndrome. METHODS. We prospectively screened 25,207 women and adolescents in the second trimester of pregnancy and assigned each a risk of fetal Down's syndrome with an algorithm that took into account measurements of all three serum markers in combination with maternal age. On this basis, 1661 subjects (6.6 percent) were initially assigned a second-trimester risk of fetal Down's syndrome of at least 1 in 190, and 962 (3.8 percent) were offered amniocentesis for chromosomal analysis after verification of gestational age. Gestational age was determined on the basis of the first day of the last menstrual period or, when available, by ultrasonography. RESULTS. Among the 760 women and adolescents who chose amniocentesis, 20 cases of fetal Down's syndrome were detected, along with 7 other chromosomal disorders. There was 1 additional case of fetal Down's syndrome among the 202 women who chose not to have amniocentesis. The rate of detection of Down's syndrome was thus 58 percent (21 of 36 expected cases), and the frequency of identifying a fetus with Down's syndrome in women undergoing amniocentesis was 1 per 38 amniocenteses (95 percent confidence interval, 1 in 25 to 1 in 62). CONCLUSIONS. Measuring serum alpha-fetoprotein, chorionic gonadotropin, and estriol is more effective in screening for fetal Down's syndrome than measuring maternal serum alpha-fetoprotein alone. Such an expanded protocol can readily be incorporated into existing prenatal screening programs.     

Second-trimester maternal serum screening for Down's syndrome: free beta-human chorionic gonadotrophin (HCG) and alpha-fetoprotein, with or without unconjugated oestriol, compared with total HCG, alpha- fetoprotein and unconjugated oestriol

The aim of our study was to compare three protocols for second- trimester maternal serum screening for Down's syndrome in the same serum samples, using two triple tests [total human chorionic gonadotrophin (HCG), alpha-fetoprotein, unconjugated oestriol; and free beta-HCG, alpha-fetoprotein, unconjugated oestriol] and a double test (free beta-HCG and alpha-fetoprotein). The three protocols were compared in a series of 23 serum samples from Down's syndrome pregnancies and in a cohort of 2516 pregnant women receiving routine antenatal care between June 1992 and June 1993. Among the 23 affected cases, at a cut-off risk of 1:380, the detection rate of Down's syndrome was comparable with the double test (74%; 17/23) and the triple tests (65%; 15/23) (not significantly different). At the same cut-off risk, in the cohort of 2516 pregnant women screened between 15 and 18 weeks gestation, both protocols using free beta-HCG achieved a significant reduction of the number of false positive cases (P = 0.013 and 0.004 for double and triple tests respectively). We conclude that, compared to total HCG, alpha-fetoprotein and unconjugated oestriol, use of free beta-HCG and alpha-fetoprotein represents a better second- trimester screening test for Down's syndrome, because it significantly decreases the false positive rate at a lower running cost. The addition of unconjugated oestriol to the double test adds no further advantage.      

Screening for fetal Down's syndrome in pregnancy by measuring maternal serum alpha-fetoprotein levels

Although the risk of Down's syndrome increases with maternal age, women under 35 bear about 80 percent of the infants born with this condition. We prospectively investigated the utility of measuring maternal serum alpha-fetoprotein during the second trimester in women under 35 in order to identify pregnancies in which the fetus was affected with Down's syndrome. Over a two-year period, 34,354 women in this age group were screened. Amniocentesis was offered when the risk of Down's syndrome, calculated as a function of maternal age and maternal serum alpha-fetoprotein concentration adjusted for maternal weight and race, was 1:270 or higher, the risk for a 35-year-old woman. This threshold was exceeded in 1451 women in whom gestational age was confirmed by ultrasound; 9 women in this group had a fetus with the syndrome. In three women whose fetuses had trisomy 18 and one whose fetus had trisomy 13, the calculated risk of Down's syndrome was 1:270 or higher. Thus, among women in whom the risk exceeded our cutoff point, 1 in 161 were found to have a pregnancy in which the fetus was affected with Down's syndrome; the figure was 1 in 112 for all autosomal trisomies. Eighteen pregnancies involving Down's syndrome, three involving trisomy 18, and two involving trisomy 13 were not associated with a calculated risk above the cutoff point. The available data indicate that in our population, using a cutoff for risk at which 5 percent of women under 35 are offered amniocentesis, we will detect one quarter to one third of pregnancies in which the fetus has Down's syndrome.     

Alphafetoprotein in midtrimester Down''s syndrome fetal serum.

Serum alphafetoprotein was estimated in fetuses with and without Down's syndrome or with other chromosome abnormalities from the 17th to the 28th week of pregnancy. In normal fetuses, the AFP level declines steadily during this period. Before 20 weeks, there was no difference in the serum AFP levels of the three groups of fetuses. After 20 weeks, the serum AFP level in cases of Down's syndrome declined more rapidly than normal. This was not observed in fetuses with other chromosome abnormalities. This suggests that low maternal serum alphafetoprotein levels used for prenatal screening for Down's syndrome in the early second trimester cannot be explained by low levels in the Down's fetuses themselves.     

Down's syndrome and maternal cancer. A preliminary study

The possible association between maternal cancer and Down's syndrome was studied in a register-based case-control study of 962 women who had an infant with Down's syndrome born during 1973-1981, and to each two controls, matched for maternal age, parity, and year of delivery. A total of 952 complete triplets was obtained. Among them, 63 Down's syndrome mothers and 79 control mothers were found in a cancer registry for the period 1958-1982 (odds ratio 1.6;95% conf. interval 1.3-2.0). Of these, 14 Down's syndrome mothers and 20 controls had malignant lesions (odds ratio 1.4, 0.9-2.2), and 49 Down's syndrome mothers and 55 controls had cervical cancer in situ (odds ratio 1.8, 1.4-2.3). This risk increase was present both before and after the delivery of the Down's syndrome infant. Various explanations of these findings are discussed and the need for further data is stressed.     

Nuchal translucency measurement and pregnancy outcome after assisted conception versus spontaneously conceived twins

BACKGROUND: Nuchal translucency (NT) measurement for Down's syndrome screening or detecting various fetal anomalies is a reliable sonographic marker. This study evaluates the contribution of NT screening in spontaneously conceived and assisted conception twin pregnancies. METHODS AND RESULTS: Maternal age at measurement, chorionicity, ultrasound features, karyotype results and pregnancy outcome were recorded prospectively and compared in 83 assisted reproduction treatment and 91 spontaneously conceived twins. Pregnancy outcome was evaluated according to maternal age, method of conception, NT data and chorionicity. NT measurements (> or =95 centiles of the normal range) were considered screen-positive and mid-pregnancy fetal karyotyping was advised. Complicated pregnancy outcome, which could be signalled by increased NT, was defined as either chromosomal abnormalities, severe structural defects or fetal demise. Based on NT measurements, 16 fetuses (4.6%) were found to be screen-positive. Five of them had chromosomal aneuploidy and selective termination was performed. The parents also opted for this procedure in another five fetuses because of major structural abnormality diagnosed during NT assessment. No other chromosomal or major fetal abnormality were found post-natally. Although no difference was found in NT, crown-rump length and maternal age between spontaneous and assisted reproduction technology twin pregnancies, the former group had a significantly higher rate of screen-positive results (7 versus 2%, P = 0.047), amniocentesis uptake (33 versus 22%, P = 0.014), monochorionic twining (32 versus 4%, P = 0.001) and complicated pregnancy outcome (11 versus 5%, P = 0.02). CONCLUSION: The present study confirms that first trimester target scanning can improve outcome by early detection and management of cases with an anomalous co-twin. It also identifies some differences between spontaneously and artificially conceived twin pregnancies in relation to this area of testing.     

First trimester biochemical screening for Down's syndrome in singleton pregnancies conceived by assisted reproduction

BACKGROUND: Serum biochemical markers [free betahCG (fbetahCG); pregnancy-associated plasma protein-A (PAPP-A)] used in first trimester Down's syndrome screening have not been fully investigated in pregnancies achieved by assisted reproduction techniques. We present data on pregnancies conceived by all types of assisted reproduction techniques, including pregnancies following ovum donation (OD) and a large sample by ICSI. METHODS: First trimester Down's syndrome screening was performed in 1054 normal singleton pregnancies: natural conception (n = 498), ovulation induction (OS, n = 97), IVF (n = 47), ICSI (n = 222) and OD (n = 190). RESULTS: No differences in maternal levels of fbetahCG and PAPP-A, measured by the Kryptor system, appeared between naturally conceived pregnancies (n = 498) and those obtained with assisted reproduction techniques (n = 556). Several differences were apparent when comparing fbetahCG levels between different technologies but PAPP-A levels only differed between OS and IVF pregnancies (P < 0.05). In a further small study, no differences were observed using frozen embryos (n = 37), preimplantation genetic diagnosis (n = 53) or sperm from testicular biopsy (n = 21). CONCLUSIONS: Data accumulated so far suggest that first trimester biochemical markers either do not need any adjustments (e.g. in pregnancies obtained after OS and ICSI), or have very little impact (e.g. IVF pregnancies) or no impact (e.g. OD pregnancies) on the false positive rates.