双胎妊娠胎儿染色体非整倍体产前筛查的研究进展

双胎妊娠胎儿染色体非整倍体疾病的发生率较单胎妊娠高,同时其筛查受到很多因素的影响。双胎妊娠的合子性质非常重要,直接影响风险率的计算模式,临床实践中多以妊娠早期绒毛膜性间接判断。目前双胎妊娠染色体非整倍体疾病筛查方案集中在妊娠早期胎儿颈部半透明层厚度(nuchal translucency,NT)筛查、妊娠早期联合筛查(NT+血清学筛查)、妊娠中期血清学筛查以及利用无创产前检测技术(noninvasive prenatal test,NIPT)进行胎儿染色体非整倍体疾病筛查。这些方案主要涉及染色体疾病中发病率较高的21-三体综合征和18-三体综合征。考虑到检出率、假阳性率以及经济学效应,妊娠早期联合筛查为目前双胎妊娠染色体非整倍体疾病筛查的主要方案,对近年来双胎妊娠染色体非整倍体产前筛查研究进展进行综述。     

Der nichtinvasive Pränataltest (NIPT) sinnvoll eingesetzt

The detection rate for Down’s syndrome using non-invasive prenatal testing (NIPT) is 99.2?%, which exceeds the rate for first trimester screening but does not fulfill the criteria for an adequate  diagnosis. The fetal examination by ultrasound during first trimester screening also allows a differentiated assessment of the fetus and is indispensable because congenital abnormalities are much more common than chromosome aberrations. Furthermore, assessment of additional sonographic markers during first trimester screening allows a precise classification into risk groups. The NIPT is most useful in the intermediate risk group. Correct interpretation of the results and counselling of the pregnant women are crucial for correct selection of further diagnostic steps.     

孕中期联合血清学和NIPT进行唐氏综合征筛查的回顾性分析

目的:探讨联合孕中期血清学筛查(second trimester serum screening,STSS)和胎儿染色体非整倍体无创DNA产前检测(noninvasive prenatal testing,NIPT)进行唐氏综合征(Down syndrome,DS)筛查在天津地区的临床应用价值。方法:对10 429例15~20~(+6)周妊娠妇女进行二联STSS,设定1/270为DS高风险切割值,所有妊娠妇女均具有妊娠结局随访记录。对二联STSS结果为DS高风险的妊娠妇女建议羊膜腔穿刺,同时告知NIPT的范围及局限性,由妊娠妇女自愿选择;建议二联STSS风险值在1/1 000~1/270之间(含1/1 000)的低风险妊娠妇女,及风险值小于1/1 000的高龄(预产期年龄≥35岁)妊娠妇女行NIPT。联合筛查结果以NIPT结果为最终筛查结果,若妊娠妇女没有进行NIPT,以二联STSS结果为最终筛查结果。结果:二联STSS的DS检出率为73.33%(11/15),假阳性率5.75%(600/10 429),阳性预测值为1.80%(11/611);NIPT的DS检出率为100%(13/13),阳性预测值为100%(13/13);孕中期联合筛查的DS检出率为93.33%(14/15),假阳性率为1.62%(169/10 429),阳性预测值为7.65%(14/183),较单纯二联STSS方案DS阳性预测值有所提高(P=0.000)。结论:联合STSS和NIPT的DS筛查能够提高二联STSS的阳性预测值,减少因侵入性产前诊断造成的胎儿流产,为天津地区提供可参考的DS产前筛查方案。     

An Update on Current Prenatal Testing Options: First Trimester and Noninvasive Prenatal Testing

Prenatal genetic testing is rapidly evolving and requires that prenatal care providers stay up‐to‐date with accurate, evidence‐based knowledge. Noninvasive prenatal testing (NIPT), first trimester maternal serum markers, and fetal nuchal translucency are the most recently developed screening tests added to the testing repertoire for detection of chromosomal disorders such as trisomy 21 (Down syndrome). NIPT is a new, highly accurate technique that uses maternal serum and is rapidly being introduced as a first trimester screening tool and increasingly being requested by pregnant women. The American College of Obstetricians and Gynecologists recommends that all pregnant women be offered first and second trimester screening options, regardless of risk status, but does not yet recommend NIPT. It is important for prenatal care providers to be aware of and understand these testing options in order to assist women and their families in making well‐informed decisions during pregnancy. The purpose of this article is to update midwives and other prenatal care providers on the current prenatal genetic testing options available and how to appropriately offer and discuss them with their clients. We discuss how these tests work; what to do with the results; and most importantly, how to support and communicate accurate information to women and families as they navigate through an increasingly complicated array of testing choices.     

Second trimester serum markers

Prenatal screening for Down syndrome in the early second trimester with multiple maternal serum markers has been available for more than 15 years. The multiple marker combination with the highest screening performance currently available is alpha-fetoprotein (AFP), unconjugated estriol (uE3), human chorionic gonadotropin (hCG), and inhibin A, together with maternal age (so-called quad marker test). With this combination, a detection rate of 80% at a 5% false positive rate is achieved. Inhibin A, the newest addition to second trimester serum screening, is an alpha-beta subunit hormone of placental origin, and is measured using a monoclonal two-site ELISA validated for use in prenatal screening. Quality control parameters for inhibin A measurement are acceptable and are monitored through the proficiency testing program administered by the College of American Pathologists. Research into other possible second trimester screening markers has included studies on the maternal urine and serum levels of an hCG variant, hyperglosylated hCG (h-hCG; invasive trophoblast antigen). Recent data indicate that h-hCG is similar to hCG itself, although its measurement in maternal urine may improve the performance of the established serum marker combinations. With the introduction of first trimester screening markers and their use in an integrated first and second trimester marker approach to screening, and with the fact that many women do not seek prenatal care until the early second trimester, prenatal screening for Down syndrome using second trimester serum markers remains a major resource in obstetrical care.     

First trimester screening for aneuploidy: Nuchal translucency sonography

Prenatal diagnosis of fetal aneuploidy is a continuously and rapidly evolving area of research. Currently in the United States, the standard of care for screening pregnancies for aneuploidy involves assessment of maternal age together with the use of multiple second trimester maternal serum markers. This screening approach identifies approximately 60% of pregnancies with fetuses affected with Down syndrome and provides results in the second trimester of pregnancy. First trimester screening for aneuploidy by using nuchal translucency sonography is one of the most promising areas of research in the detection of Down syndrome. This screening method involves measuring the normal space located between the cervical spine and overlying fetal skin at 10 to 14 weeks' gestation. Studies from both high risk and unselected patient populations suggest significant advantages to this approach for Down syndrome detection compared with currently available second trimester screening methods. The combination of first trimester biochemical screening and nuchal translucency measurements may further improve the efficacy of prenatal screening for aneuploidy. The article reviews studies suggesting a role for nuchal-translucency-based aneuploidy screening and describes areas of ongoing research in this field.     

First trimester combined test for Down syndrome screening in unselected pregnancies — A report of a 13-year experience

ObjectiveTo analyze the performance of the first trimester Down syndrome screening in a single medical center in Northern Taiwan.Materials and methodsFrom April 1999 to June 2012, a total of 25,104 pregnant women at gestational age of 10 weeks to 13 weeks 6 days received first trimester “combined test” for Down syndrome screening. The test combines the ultrasound scan of nuchal translucency thickness and maternal biochemical serum levels of pregnancy-associated plasma protein A (PAPP-A) and free beta-human chorionic gonadotropin (β-hCG). A positive screen was defined as an estimated Down syndrome risk ≥1/270, and either chorionic villous sampling or amniocentesis was performed for fetal chromosomal analyses.ResultsSeventy-eight of the 25,104 pregnancies were proven to have fetal chromosome anomalies. The detection rates for trisomy 21, trisomy 18, Turner syndrome, and other chromosome anomalies were 87.5% (21/24), 69.2% (9/13), 81.8% (9/11), and 60% (18/30), respectively, with a false positive rate (FPR) of 5.4% (1353/25,026). Further evaluation of the detection rates for trisomy 21, by gestational age at 11, 12, and 13 weeks, were 92.3%, 87.5%, and 66.7%, respectively.ConclusionThe first trimester combined test is an effective screening tool for Down syndrome detection with an acceptable low false positive rate. The best timing of screening will be between 11 and 12 weeks' gestation.     

Down syndrome screening in France: the worst consensus

Down syndrome screening has been based on second trimester maternal serum markers assay for many years. Another late strategy was based on the "genetic sonogram" performed in early second trimester in high-risk populations selected on maternal age or second trimester maternal serum markers. New strategies for Down syndrome screening have emerged over the last 10 years, with higher sensitivity and lower false-positive rates. First trimester ultrasound examination is a successful screening test; the sensitivity of nuchal translucency measurement is of 60 to 77% for a 5% false-positive rate. Combining nuchal translucency measurement with PAPP-A and free beta-hCG assay (first trimester combined screening) increases the sensitivity up to 82%. The most specific strategy is based on the integrated test, i.e., the integration of the quadruple test performed in second trimester (inhibine dimeric A, total beta-hCG, AFP, and uE3 assay) to the first trimester combined screening: for a 85% detection rate, the false-positive rate is estimated to 0.9%. However, it is ethical only with the patient agreement because it prevents access to the results of first trimester combined screening, and deprives the patient of an early diagnosis by CVS. Therefore, alternative strategies were proposed: step-wise sequential screening and contingent sequential screening. In the step-wise screening, karyotype is offered when the result of the combined test is beyond a specified threshold. If the combined test result is below this threshold, quadruple test is offered, and the final risk is calculated in the second trimester by integrating the results of the quadruple test with those of the combined test. Contingent screening also begins with the first trimester-combined test. According to its results, the patients are considered in one of the 3 following risk groups: high, intermediate, or low risk. An early karyotype is proposed to the high-risk group after combined testing. The low risk group is reassured and thus the quadruple test is not performed. The quadruple test is proposed to the intermediate risk group and final risk is calculated by the integration of the combined test result into the quadruple test result. The global detection rate of the step-wise or contingent sequential screening is estimated to 84% for a false-positive rate of 2%.     

Screening for Down syndrome

Down screening has been available within clinical practice for over 50 years during which time significant innovation and exciting new advances have improved the accuracy and safety of screening, and improved choice for women who are considering antenatal screening for Down syndrome. The UK National Screening Committee is responsible for setting the national standards regarding screening and it has steadily and consistently directed and facilitated an increase in the detection rate whilst minimising the screen positive rate of Down syndrome screening. This has reduced the number of false positive results and consequently the number of invasive diagnostic procedures and their related miscarriages. Non-invasive pre-natal testing (NIPT) using cell free DNA is a rapidly evolving field and it will soon be incorporated into the existing NHS antenatal screening programme for aneuploidy. It will be offered to women who receive a ‘high risk’ result following current screening methods (combined test or quadruple test), and will further reduce the number of invasive tests performed, whilst maintaining current detection rates.     

Prospective evaluation of a first trimester screening program for Down syndrome and other chromosomal abnormalities using maternal age, nuchal translucency and biochemistry in an Australian population

BACKGROUND: A combination of maternal age and ultrasound assessment of the nuchal translucency (NT) has been used in the first trimester to screen for chromosomal abnormality. In the United Kingdom, the addition of NT screening was shown to be beneficial. AIMS: To report the sensitivity of combined first trimester biochemistry and ultrasound screening for Down syndrome in an Australian private practice specialising in obstetric ultrasound. METHODS: A prospective study in a private obstetric ultrasound practice. Over 22 months, 2121 patients were screened and data was analysed for sensitivity (detection) and false positive rates for all chromosome abnormalities. RESULTS: There were 17 chromosomal abnormalities, five of which were Down syndrome. Using maternal age alone or age and biochemistry, four of the Down syndrome cases were detected for a 29 and 19% false positive rate, respectively. Using age and NT or age, NT and biochemistry, all the Down syndrome cases were detected, for a false positive rate of 5.7 and 7.2%, respectively. The difference in detection rates for Down syndrome or other chromosomal abnormalities, using the four screening methods, did not reach statistical significance. However, the false positive rates in screening methods without ultrasound to assess the NT was significantly higher (P < 0.01). CONCLUSIONS: A combination of maternal age, NT and maternal serum biochemistry gives a high detection rate for both trisomy 21 and other chromosomal abnormalities. Down syndrome screening using either maternal age alone or age in combination with first trimester biochemistry conferred screen positive rates significantly higher than when combined with NT.     

染色体微阵列分析在无创产前筛查非整倍体高风险中的应用价值

目的:探讨染色体微阵列分析(CMA)技术在无创产前筛查(NIPT)提示非整倍体高风险胎儿的产前诊断中的应用价值。方法:241例NIPT提示胎儿染色体非整倍体高风险的孕妇,经羊膜腔或绒毛穿刺获取胎儿细胞,进行CMA分析。对于NIPT提示21-三体和性染色体非整倍体高风险的孕妇根据筛查原因(高龄筛查组、唐筛异常或超声软指标异常组、非高龄筛查组)进行组间NIPT阳性预测值的比较,并对CMA检测提示有染色体拷贝数变异(CNV)的病例进行致病性分析。结果:NIPT对于染色体非整倍体总的阳性预测值为76.3%。NIPT对于21-三体、18-三体、13-三体和性染色体非整倍体的阳性预测值分别为95.0%、88.8%、75.0%和53.3%。经CMA分析确认,在101例NIPT提示21-三体高风险病例中,以高龄筛查组阳性预测值最高(100.0%),3组间比较,差异有统计学意义(P=0.001)。在90例NIPT提示性染色体非整倍体高风险病例中,仍以高龄筛查组阳性预测值最高(61.9%),3组间比较,差异有统计学意义(P=0.002)。12例NIPT提示染色体非整倍体高风险经CMA检测存在CNV。结论:对于21-三体和性染色体非整倍体,不同人群中高龄组的NIPT阳性预测值最为显著,临床上对于此类人群,更要引起足够的重视,做好跟踪随访。CMA较传统的染色体核型分析能额外检出CNV,更能提高染色体结构异常的检出率。     

Prenatal screening for common aneuploides

Down syndrome screening has been available within clinical practice for over 50 years within which time significant innovation and exciting new advances have improved the accuracy, safety, and choice for women who are considering antenatal screening for Down syndrome. The UK National Screening Committee is responsible for setting the national standards regarding screening and it has steadily and consistently directed and facilitated an increase in the detection rate whilst minimising the screen positive rate. This has reduced the number of false positive results and consequently the number of invasive diagnostic procedures and their related miscarriages. Non-invasive pre-natal testing (NIPT) using cell free DNA is a rapidly evolving field and it will soon be incorporated into the existing NHS antenatal screening programme for aneuploidy. It will be offered to women who receive a ‘high risk’ result following current screening methods (combined test or quadruple test), and will further reduce the number of invasive tests performed, whilst maintaining current detection rates.     

Second trimester ultrasound screening for chromosomal abnormalities

The use of prenatal ultrasound has proven efficacious for the prenatal diagnosis of chromosomal abnormalities. The first sonographic sign of Down syndrome, the thickened nuchal fold, was first described in 1985. Since that time, multiple sonographically-identified markers have been described as associated with Down syndrome. The genetic sonogram, involving a detailed search for sonographic signs of aneuploidy, can be used to both identify fetuses at high risk for aneuploidy and, when normal, can be used to decrease the risk for aneuploidy for a pregnancy when no sonographic markers are identified. Combining the genetic sonogram with maternal serum screening may be the best method of assessing aneuploidy risk for women who desire such an assessment in the second trimester. Trisomy 18, Trisomy 13, and triploidy are typically associated with sonographically identified abnormalities and have a high prenatal detection rate. The use of the described sonographic signs in low-risk women requires further investigation, however, patients at increased risk for aneuploidy due to advanced maternal age or abnormal serum screening can benefit from a genetic sonogram screening for sonographic signs of aneuploidy to adjust their baseline risk of an affected fetus.     

Introduction of non-invasive prenatal testing as a first-tier aneuploidy screening test: A survey among Dutch midwives about their role as counsellors

In 2014, non-invasive prenatal testing (NIPT) for trisomies 21, 18 and 13 was added to the Dutch prenatal screening program as part of the TRIDENT study. Most (85%) pregnant Dutch women are counselled for prenatal aneuploidy screening by primary care midwives. This will remain when NIPT is implemented as a first-tier screening test. We therefore investigated midwife counsellors’: 1) Knowledge about NIPT; 2) Attitudes towards NIPT as first-tier screening test; and 3) Experiences with informing clients about NIPT. Between April-June 2015, an online questionnaire to assess knowledge about NIPT, attitudes towards NIPT, and experiences with NIPT was completed by 436 Dutch primary care midwives. We found that 59% midwives answered ≥7 of 8 knowledge questions correctly. Continuing professional education attendance and more positive attitudes towards prenatal screening for Down syndrome were positively associated with the total knowledge score (β = 0.261; p = 0.007 and β = 0.204; p = 0.015, respectively). The majority (67%) were in favor of replacing First trimester Combined Test with NIPT, although 41% preferred to maintain a nuchal translucency measurement alongside NIPT. We conclude that midwives demonstrated solid knowledge about NIPT that may still be improved in some areas. Dutch midwives overwhelmingly support the integration of NIPT as a first-tier screening test.     

Patient and health professional acceptance of integrated serum screening for Down syndrome

Integrated testing for Down syndrome combines first trimester maternal serum and nuchal translucency (NT) measurements with second trimester maternal serum measurements into a single second trimester Down syndrome risk. A variant of integrated testing, the integrated serum test, requires only the serum measurements and may be more suitable for widespread use in the general pregnancy population. Concern has been voiced that women will find the delay associated with waiting for screening results unacceptable for either fully integrated (including NT measurements) or integrated serum testing. To address this issue, we surveyed 60 women from a population of 8773 women enrolled in an integrated serum screening intervention trial in Maine. The women all had also undergone traditional second trimester screening 1 to 2 years earlier. All 60 women remembered having the integrated serum test, and 59 remembered having a prenatal test in their previous pregnancy. Three-quarters of women did not experience anxiety relating to the wait for final results in the second trimester, and 95% would consider being screened by the integrated serum test in a future pregnancy. Women receiving prenatal care at the primary care level are prepared to wait until the second trimester for more accurate Down syndrome risk estimates on which to base their decision-making.     

Second trimester maternal serum screening using alpha fetoprotein, free beta human chorionic gonadotropin and maternal age specific risk: result of chromosomal abnormalities detected in screen positive for Down syndrome in an Asian population.

BACKGROUND: This study was to determine the incidence of chromosome abnormalities in Taiwanese women undergoing prenatal chromosome analysis after a second trimester Down syndrome screening by using maternal age and serum dual-marker testing (alpha-fetoprotein and free-beta unit human chorionic gonadotropin). METHODS: A total of 10,098 Taiwanese women with pregnancy between 15 and 23 weeks' gestation received second-trimester Down syndrome risk evaluation by dual-marker and maternal age specific risk testing in a single medical center. The study took 22 months. Ninety-seven percent of this study population was less than 34 years old. Ninety-six percent of our cases were screened between 15-20 weeks of gestation. This population was included only after a routine ultrasonography scan for correction of gestational age and exclusion of major structural anomalies. By using an algorithm to detect Down's syndrome, with a risk of 1:270 as a cut-off value, 816 patients were screen-positive for Down syndrome (screen-positive rate 8.0%). Karyotypes were reviewed for 670 (82.1%) mothers who received prenatal karyotype analysis. RESULTS: Twelve cases of Down syndrome were identified in the screen positive group with an estimated detection rate of 67% (false positive rate 8%). Three cases of Down syndrome were detected in late trimester among the screen-negative group. Seven other fetal chromosome abnormalities were also found among the screen-positive pregnancy. In addition, seven cases were screen-positive for trisomy 18; all of these patients received amniocentesis and only one case was confirmed. CONCLUSION: These findings indicate that this screening program combining alpha-fetoprotein (AFP), free beta human chorionic gonadotropin (free-hCG) and maternal age-specific would achieve a screening efficiency in Taiwanese populations as comparable to those obtained in Caucasian populations. Our results also suggest that approximately 3% of pregnancies with a positive dual marker and maternal age-specific screen results will have a chromosome abnormality despite having a normal routine ultrasound scan. Mothers with positive screening results should be made aware of the implications of a positive result.     

无创基因检测筛查胎儿染色体异常的效果及其与孕妇年龄和检测孕周相关性的探讨

目的分析我院无创基因检测对胎儿常见染色体非整倍体异常的检测效果,探讨不同检测孕周、孕妇年龄与检测效果指标的相关性。 方法选择自2013年6月至2019年4月在北京大学深圳医院行无创产前基因检测(non-invasive prenatal DNA testing, NIPT)的孕妇,对检测结果高风险者进行羊水染色体核型分析,对检测低风险者行电话随访,以核型分析和随访结果判断胎儿是否异常,分析NIPT的检测效果指标。按孕妇年龄分为<30岁、30~34岁、35~39岁和≥40岁4个各组,按检测孕周分为≤13⁺⁶、14~22⁺⁶周、23~27⁺⁶周和≥28周4个组,探讨灵敏度、特异度、阳性预测值、假阳性率等指标与孕妇年龄及检测孕周的相关性。 结果(1)共43 918例行NIPT孕妇纳入统计,NIPT总体的灵敏度100.00%,特异度99.76%,假阳性率0.24%;(2)NIPT对第21、18、13及性染色体异常的灵敏度、特异度均在99%以上,假阳性率低于0.5%;(3)年龄分组中35~39岁组与30~34岁组的特异度(99.67% vs 99.81%)相比,差异有统计学意义( χ²＝4.099,P＝0.043),其余筛查指标差异均没有统计学意义。孕周分组数据筛选指标比较,差异均没有统计学意义(P>0.05);(4)假阳性病例中发现2例新生儿患有先天性心脏病,1例新生儿双肾盂轻度分离,1例多发畸形等非染色体畸形异常。 结论NIPT对常见染色体非整倍体异常具有较高的准确性及特异性,较低的假阳性率,特别是21-三体。NIPT对于不同年龄、不同孕周的孕妇检测效果差异不大。对于NIPT结果阳性病例,需警惕胎儿非染色体畸形等异常的发生。     

Nichtinvasive Pränataltestung (NIPT)

Non-invasive prenatal testing (NIPT) using cell-free fetal DNA (cff-DNA) in maternal blood has the potential to dramatically alter the way prenatal screening and diagnosis is delivered. Before NIPT can be implemented into routine practice, information is required on its costs and benefits. The best performing screening tests are able to identify more than 90?% of trisomy 21 cases with a 5?% rate of false positives but positive screening results require confirmation with diagnostic testing, such as amniocentesis or chorionic villus sampling (CVS). However, both sampling procedures are invasive, and are associated with significant risks to the fetus and mother, including the potential loss of a healthy fetus. For this reason invasive prenatal diagnosis tests are currently performed only in high-risk pregnancies or in pregnancies with increased maternal age and/or a family history of inherited disease. Therefore, developing a reliable method for NIPD for fetal trisomy 21 is of critical importance in prenatal care and NIPT is able to identify 99?% of trisomy 21 cases with a 0.1?% rate of false positives. As first-line testing NIPT detects more Down’s syndrome cases, results in fewer procedure-related miscarriages and is more expensive than current screening. When NIPT uptake increases, NIPT will detect more trisomy 21 cases with a small increase in procedure-related miscarriages and costs. As first-line testing NIPT is likely to produce more favorable outcomes but at greater cost. Further research is needed to evaluate NIPT under real world conditions.     

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.     

1p deletion syndrome: A prenatal diagnosis characterized by an abnormal 1st trimester combined screening test,yet a normal NIPT result

Objective

To present a case with prenatal diagnosis and cytogenetic characterization of 1p36 deletion syndrome whose first trimester combined testing is abnormal but a normal NIPT result.