胎儿颈部半透明膜厚度测定筛查胎儿染色体异常

目的探讨孕早期筛查胎儿染色体异常的方案.方法 2241例孕龄在11～14w单胎妊娠的孕妇接受筛查.采用腹式或阴式B型超声波测量胎儿颈部半透明膜(NT)厚度;根据所测NT数据结合孕妇年龄由计算机算出胎儿染色体异常风险率.对所筛查出的高风险胎儿则进一步进行产前诊断(羊水细胞染色体核型分析).结果共筛查出26例染色体异常,包括Down综合征16例(61.54%)、性染色体数目异常6例(23.08%)、染色体结构异常4例(15.38%).所有接受筛查的孕妇中风险大于1/250者344例(15.35%);染色体异常检出率为80.77%,假阳性率为6.50%;21三体检出率为87.50%.结论孕早期NT 孕妇年龄二联筛查方案对孕早期临床筛查胎儿染色体异常有较好的实用价值.     

Aneuploidy screening in the first trimester

This article reviews the performance of first trimester screening for chromosomal anomalies using various combinations of ultrasound and maternal serum biochemical modalities. Detection rates in excess of 90% can be routinely achieved for Trisomy 21, Trisomy 13, Trisomy 18 using a combination of fetal nuchal translucency (NT) thickness and maternal serum free ss-hCG and PAPP-A at 11 + 0 to 13 + 6 weeks of gestation.     

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.     

超声测量胎儿颈项透明层厚度在产前筛查中的应用

产前筛查是目前诊断胎儿畸形的必要手段,胎儿颈项透明层（nuchal translucency,NT）增厚与胎儿染色体异常、先天性心脏病、自然流产等不良临床结局密切相关,孕11-13＋6w超声测量胎儿颈项透明层（NT）厚度是孕早期诊断胎儿畸形最有意义的一项检查,特别是筛查染色体异常的较敏感的指标。为了明确超声测定胎儿颈项透明层厚度在产前诊断中的意义,现就国内外文献对胎儿颈项透明层与产前超声的关系进行综述。     

The distribution of fetal nuchal translucency thickness in normal Korean fetuses

The aim of present study was to establish normative data for the distribution of nuchal translucency (NT) thickness in normal Korean fetuses. The data were collected from pregnant women with singleton pregnancies in whom fetal ultrasound was performed and the fetal NT thickness was measured between 11 and 14 weeks of gestation. Among them, a total of 2,577 fetuses with a known normal outcome were included in this study. The distribution of multiple of median (MoM) values of the NT thickness with crown-rump length (CRL) in 10-mm intervals and the 95th percentile of MoM were calculated with the linear regression method. The present study showed that NT measurements increase with increasing CRL and a false positive rate increases with increasing gestational age. Therefore, a fixed cut-off point through the first trimester was not appropriate and each NT measurement should be examined according to the gestational age. The present study offers normative data of the fetal NT thickness in a Korean population, which can be used as reference for screening chromosomal aberrations or other congenital abnormalities in the first trimester.     

Robust border enhancement and detection for measurement of fetal nuchal translucency in ultrasound images

Ultrasonic measurement of nuchal translucency (NT) thickness in the first trimester of pregnancy has recently been proposed as the most useful marker in early screening for fetal chromosomal abnormalities. However, manual tracing of the two echogenic lines in the image, using on-screen calipers, is hampered by weak edges, together with noise and other artifacts, leading to variable results and inefficiency. Our semi-automatic method of fetal NT thickness measurement uses a coherence-enhancing diffusion filter to enhance the border and reduce noise, followed by detection of the NT by minimization of a cost function, that combines intensity, edge strength and continuity, using dynamic programming. This method has been validated by determining the correlation between manual and semi-automatic measurements.     

Risk and uncertainty: Shifting decision making for aneuploidy screening to the first trimester of pregnancy

PurposeThe clinical introduction of first trimester aneuploidy screening uniquely challenges the informed consent process for both patients and providers. This study investigated key aspects of the decision-making process for this new form of prenatal genetic screening.MethodsQualitative data were collected by nine focus groups that comprised women of different reproductive histories (N = 46 participants). Discussions explored themes regarding patient decision making for first trimester aneuploidy screening. Sessions were audio recorded, transcribed, coded, and analyzed to identify themes.ResultsMultiple levels of uncertainty characterize the decision-making process for first trimester aneuploidy screening. Baseline levels of uncertainty existed for participants in the context of an early pregnancy and the debate about the benefit of fetal genetic testing in general. Additional sources of uncertainty during the decision-making process were generated from weighing the advantages and disadvantages of initiating screening in the first trimester as opposed to waiting until the second. Questions of the quality and quantity of information and the perceived benefit of earlier access to fetal information were leading themes. Barriers to access prenatal care in early pregnancy presented participants with additional concerns about the ability to make informed decisions about prenatal genetic testing.ConclusionsThe option of the first trimester aneuploidy screening test in early pregnancy generates decision-making uncertainty that can interfere with the informed consent process. Mechanisms must be developed to facilitate informed decision making for this new form of prenatal genetic screening.     

Ultrasound screening for fetal chromosome anomalies

Ultrasound evidence for aneuploidy may be found in almost every organ of the fetus and can be used to modify the risk of aneuploidy. The diagnosis of these minor anomalies on second-trimester ultrasonography will increase the risk of an abnormal karyotype whereas the absence of these findings may reduce this danger. The most specific and most ominous isolated markers for fetal aneuploidy are nuchal findings (edema or cysts), indicating the need to obtain a fetal karyotype in all cases irrespective of maternal age or results of biochemical serum screening. Hyperechoic fetal bowel is apparently also a strong indicator of fetal aneuploidy. Other isolated sonographic markers may increase the risk of an abnormal karyotype three- to ninefold. Most sonographic markers for aneuploidy specify an increased risk for Down syndrome, but choroid plexus cysts are apparently more specific for trisomy 18. Along with other screening methods, ultrasound screening for fetal aneuploidy should be used routinely to identify additional pregnancies at need for evaluation of fetal karyotype.     

The effect of a 'vanishing twin' on biochemical and ultrasound first trimester screening markers for Down's syndrome in pregnancies conceived by assisted reproductive technology

BACKGROUND: Previous studies have found that 1 in 10 in vitro fertilization(IVF) singletons originates from a twin gestation. First trimesterDown's syndrome screening markers are altered in assisted reproductivetechniques (ART) pregnancies compared with spontaneously conceivedpregnancies. The presence of a perished embryo may further complicateprenatal screening among women pregnant after ART. The aim ofthis study was to assess the impact of a ‘vanishing twin’on first trimester combined biochemical and ultrasound screeningin pregnancies conceived after IVF and intracytoplasmatic sperminjection. METHODS: From a national prospective cohort study concerning first trimestercombined screening among women pregnant after ART, 56 casesof pregnancies with a vanishing twin were identified. As controlgroup 897 cases of ART singleton pregnancies were used. Allwomen completed a first trimester combined ultrasound and biochemicalscreening programme comprising serum PAPP-A and free β-hCGtogether with nuchal translucency (NT) measurement. RESULTS: There were no significant differences in geometric mean MoMfree β-hCG and PAPP-A between pregnancies with an early(gestational week <9, EVT) or late vanishing twin (gestationalweek 9–13, LVT) or singleton pregnancies (0.98, 1.13 and0.95 for free β-hCG and 0.84, 0.80 and 0.74 for PAPP-A,respectively). Likewise, no difference was seen for NT measurements.The gestational age at the time of blood sampling and NT scanwas similar for the three groups. The proportion of EVT pregnancieswith a PAPP-A and free β-hCG log₁₀MoM value below the 5th%ilesand above the 95th%iles of the value in the singleton pregnancieswere 4.3%, 4.3%, 6.4% and 8.5%, respectively, which did notconstitute a significant difference from singletons. The correspondingvalues for LVT pregnancies were 0%, 22.2%, 0% and 11.1%, respectively;however, these numbers were too small to allow for statisticalcalculations. CONCLUSIONS: First trimester biochemical screening markers in women pregnantafter ART, and with a vanished twin diagnosed at early ultrasound,do not differ from those of other ART singleton pregnancies.In cases where the fetal demise was first diagnosed at the timeof the NT scan, it is doubtful whether the serum risk assessmentis as precise as it is in singleton ART pregnancies. No differencewas seen for NT measurements.     

The second trimester genetic sonogram

The genetic sonogram, a fetal anatomic survey targeted at identifying features associated with aneuploidy, is carried out between 15 and 20 weeks' gestation. It has evolved as an adjunctive screening tool capable of further refining the individualized risk-calculation for trisomy that is based on maternal age or serum screening markers. The significance of a range of major structural anomalies and so-called "soft-markers" for trisomy, detected both in isolation and in combination, has been widely investigated. This review serves to describe the key components of the second trimester genetic sonogram and to illustrate how these markers are integrated into risk assessment for aneuploidy.     

孕中期胎儿心血管畸形超声检测NT值与染色体核型检测的关系探讨

目的探讨孕中期胎儿心血管畸形超声检测NT值与染色体核型检测的关系。方法选取2015年1月至2017年12月因胚胎发育不良(心脏发育畸形或异常)于本院行产前检测的孕妇108例,所有产妇均于孕24~35w行超声NT检查和经腹脐静脉穿刺术取胚胎绒毛组织的染色体核型检测,观察染色体核型检测情况,分析染色体核型检测正常与异常胎儿的超声NT值差异,并采用spearman相关性分析法分析胎儿超声NT值与染色体核型检测是否正常的相关性。结果108例病例中,染色体核型检测正常者30例(27.78%),染色体核型检测异常者78例(占比72.22%)。染色体核型检测正常胎儿心血管超声NT层厚值(3.83±0.54mm)低于染色体核型检测异常胎儿(4.64±0.63mm)(P<0.05)。spearman相关性分析显示,胎儿超声NT值与染色体核型检测是否正常具有明显的负相关性(r=0.871,P=0.018<0.05)。15例继续妊娠至分娩的胎儿中,10例(包括7例染色体核型检查异常胎儿)出生后心脏功能发育异常(或畸形),其余5例出生后未出现心脏功能发育异常(或畸形),且随访至12个月仍未出现心脏功能发育异常(或畸形)。结论通过染色体核型检测对心血管畸形胎儿绒毛组织进行染色体核型检测,可发现染色体中小至100Kb片段的缺失或重复,也可发现潜在致病基因序列,孕中期胎儿心血管超声检测NT值与染色体核型检测是否正常具有明显相关性,可作为心血管发育畸形胎儿染色体核型检查的参考指标,超声检测NT检查和染色体核型检测在胎儿心血管畸形的临床诊断中均具有良好的前景。     

早孕期胎儿颈项透明层厚度与绒毛染色体G显带核型的关系

目的探讨早孕期胎儿颈项透明层厚度（NT）测量与绒毛染色体核型分析联合应用的临床价值。方法回顾性分析120例早孕期行绒毛染色体核型分析的孕妇,研究其胎儿NT值与染色体核型及妊娠结局的关系。结果 120例病例中胎儿NT≤2.5 mm 76例,未检出异常核型（0%）;NT≥2.5 mm 44例,异常核型9例（20.45%）。其中,25例2.5mm≤NT≤3.5 mm的胎儿检出染色体异常1例,检出率为4%（1/25）;19例NT≥3.5mm的胎儿检出染色体异常8例,检出率为42.11%（8/19）,两组异常核型检出率的差异有统计学意义（P〈0.05）。根据NT增厚程度的不同将NT值分为2.5-3.4mm、3.5-4.4mm、4.5-5.4mm、5.5-6.4mm、≥6.5mm,其中异常核型比例分别为1/25、0/6、2/4、1/2、5/7,各组的差异具有统计学意义（P〈0.05）,可以认为不同NT值范围内的染色体异常的检出率不同或不全相同。结论胎儿NT增厚是早孕期筛查胎儿染色体非整倍体异常的有效且敏感的超声指标,绒毛活检行染色体核型分析应作为胎儿NT≥3.5mm的孕妇的首选产前诊断方法。     

11～13+6孕周与14～17+6孕周胎儿超声筛查的对比

目的 评价非选择孕妇11～13+6孕周和14～17+6孕周胎儿超声筛查的作用.方法 2002年1月至2008年4月在中山大学附属第一医院行11～17+6孕周胎儿首次产前常规超声检查共3645例患者,其中11～13+6孕周组1556例,14～17+6孕周组2089例.比较两组胎儿结构异常的检出率及畸形类型构成比.结果 11～13+6孕周组和14～17+6孕周组胎儿结构异常首次检出率分别为2.3%(36/1556)和3.3%(68/2089),差异无统计学意义.两组胎儿结构异常类型构成比差异有统计学意义(P=0.03).11～13+6孕周组胎儿畸形前3位为颈部异常(项颈透明层增厚及颈部淋巴水囊瘤)占31.6%(18/57),胎儿水肿占15.8%(9/57),前腹壁异常占12.3%(7/57).14～17+6孕周组胎儿畸形前3位为心血管系统异常占16.7%(18/108),中枢神经系统异常占14.8%(16/108),前腹壁异常占12.0%(13/108).结论 11～13+6孕周胎儿超声检查能诊断多种致死性胎儿畸形及检测各种染色体异常超声标记;14～17+6孕周胎儿超声检查可观察相对细微的胎儿结构异常.11～13+6孕周是早期胎儿超声筛查的理想时间.     

First trimester diagnosis and screening for fetal aneuploidy

Maternal serum screening for neural tube defects and fetal aneuploidy in the second trimester has been incorporated into obstetrical practice over the past two decades. Now, as a result of several multicenter trials, first trimester screening between 11 and 14 weeks has been shown to be an effective and reliable screening test for Down syndrome and trisomy 18. Benefits of first trimester screening include earlier identification of the pregnancy at risk for fetal aneuploidy and anatomic defects, in particular, cardiac anomalies, and the option of earlier diagnosis by chorionic villus sampling, if available. This policy updates the American College of Medical Genetics policy statement entitled Second Trimester Maternal Serum Screening for Fetal Open Neural Tube Defects and Aneuploidy (2004) and complements the sections of American College of Medical Genetic's Standards and Guidelines for Clinical Genetics Laboratories entitled “Prenatal screening for Down syndrome that includes first trimester biochemistry and/or ultrasound measurements.”DisclaimerThis guideline is designed primarily as an educational resource for medical geneticists and other health care providers to help them provide quality medical genetic services. Adherence to this guideline does not necessarily assure a successful medical outcome. This guideline should not be considered inclusive of all proper procedures and tests or exclusive of other procedures and tests that are reasonably directed to obtaining the same results. In determining the propriety of any specific procedure or test, the geneticist should apply his or her own professional judgment to the specific clinical circumstances presented by the individual patient or specimen. It may be prudent, however, to document in the patient's record the rationale for any significant deviation from this guideline.     

规范化早孕期超声结构筛查在诊断无脑儿及全前脑中的意义

目的探讨规范化早孕期超声筛查在胎儿无脑儿、全前脑诊断中的价值。方法常规进行孕早期超声结构筛查,所有超声筛查根据统一的标准进行,所有检查医生均获得早孕期NT资格认证,重点观察胎儿头部横切面。结果2008年1月至2010年12月间共进行早孕期超声结构筛查13 415例,共检出10例无脑儿,均为露脑畸形,所有病例为在进行常规头部横切面扫查时未发现卵圆形钙化颅骨光环,其中1例在孕11周时超声可疑露脑儿,一周后明确诊断;8例全前脑,超声表现为胎儿头部横切面正常脉络丛典型的"蝴蝶征"消失,丘脑融合,呈单一脑室结构。结论早孕期胎儿规范超声筛查可以有效的检查无脑儿、全前脑,是一种有效的筛查方法。     

Increased nuchal translucency in trisomy 13 fetuses at 10-14 weeks of gestation.

In a multicenter screening study for trisomy 21 involving ultrasonographic measurement of fetal nuchal translucency thickness (NT) at 10-14 weeks of gestation, 100,311 singleton pregnancies with a live fetus were examined. There were 46 cases of trisomy 13, and in 33 (72%) of these, the NT was above the 95th centile. The estimated risk for trisomy 21, based on maternal age-related risk for this chromosomal abnormality and fetal NT, was above 1 in 300 in 37 (80.1%) of the trisomy 13 fetuses. The fetal crown-rump length was significantly reduced, but the fetal heart rate was increased, being above the 95th centile in 64% of cases. Additionally, 24% of trisomy 13 fetuses had holoprosencephaly and 10% had exomphalos. This study has demonstrated that at 10-14 weeks of gestation, about 80% of fetuses with trisomy 13 can be identified in a screening program for trisomy 21, based on a combination of maternal age and fetal NT.     

The feasibility of nuchal translucency measurement in higher order multiple gestations achieved by assisted reproduction.

Nuchal translucency (NT) measurement for screening chromosomal abnormalities and detecting fetal anomalies is an effective ultrasonographic marker, originally developed for singleton pregnancies. This study sought to evaluate the feasibility of NT measurements in higher order multiple gestations. Pregnant patients who conceived following assisted reproduction and were carrying three or more fetuses were enrolled in the study. Each fetus was ultrasonographically assessed, a NT measurement was obtained, and the findings were used for counselling prior to any invasive procedure. In all, 24 pregnant patients, initially carrying 79 fetuses aged 10-14 weeks of gestation, were compared with 79 consecutively matched, singleton controls, naturally conceived, having similar crown-rump lengths (+/- 3 mm). NT measurements were feasible for both study and control fetuses, which exhibited similar NT measurements for 5th, 50th and 95th centiles. Also, mean NT thicknesses [measurements in mm or multiple of the medians (MOM)] were similar for both groups (1.41 +/- 0.41 and 1.35 +/- 0.39 mm respectively and 0.87 +/- 0.23 and 0.83 +/- 0.25 MOM respectively). Prenatally no chromosomal abnormalities were detected in either group, and, of those infants who had no karyotyping, no traits were observed that warranted chromosomal analysis. NT measurements are feasible in higher order multiple gestations. Since there is no other effective screening modality for these pregnancies, it seems reasonable to recommend NT measurement for antenatal screening services for higher order multiple gestations.     

Three-dimensional ultrasonography in the first trimester of human pregnancy

Our purpose was to visualize normal embryonal and fetal surface anatomical structures in the first trimester of human pregnancy by use of three-dimensional ultrasonography with a specially developed abdominal three-dimensional transducer. Four embryos and 31 fetuses of 8-13 weeks gestation were studied with a specially-developed abdominal three-dimensional transducer (3.5 MHz). This imaging system can provide conventional two-dimensional ultrasonography images and can also generate, within seconds, high-quality three-dimensional images in the surface and transparent mode with no need for an external workstation. The percentage of surface anatomical structures visualized at each gestational age interval using two-dimensional and three-dimensional ultrasonography is presented. Head and trunk were depicted in all cases. The number and the clarity of visualization of face, upper and lower extremities, hand, and foot increased with advancing gestation. The free loop of the umbilical cord was depicted in most cases. The number of depictions of abdominal cord insertion, midgut herniation, and yolk sac decreased with the increase of gestation. Genitals could not be identified in the first trimester. The ability to view some surface anatomical structures (face, hand, and foot) was better with three-dimensional ultrasonography than with two-dimensional ultrasonography. Three-dimensional ultrasonography provides a novel means for visualization of surface anatomical structures of the embryo and early fetus. These results suggest that three-dimensional ultrasonography can become an important modality in future embryological and early fetal research and in detection of embryonic and fetal developmental disorders in the first trimester of pregnancy.      

Down′s综合征：妊娠中期的早期静脉导管血流波形测定与B超筛查的价值初评

目的评价妊娠中期的早期静脉导管血流波形测定与妊娠中期遗传学超声指标与Down′s综合征的关系。方法对239例在复旦大学附属妇产科医院产科门诊登记建卡的孕妇采用GE730超声多普勒仪进行妊娠中期的早期静脉导管血流波形测定与中期妊娠遗传学超声检查和B超排畸筛查,并建议有异常发现者行羊水穿刺染色体检查。所有孕妇均追踪随访至分娩。采用的统计方法为Bayes判别函数分析和方差分析。结果239例受检孕妇中有154例接受妊娠中期的早期静脉导管血流波形测定,157例进行妊娠中期B超筛查,接受羊水穿刺染色体检查者106例,其中有2例为Down′s儿,行中期引产。B超筛查中发现胎儿颈项软组织增厚14例,肠管回声增强6例,脉络膜囊肿7例,心室强光点5例,肾盂增宽5例,胎儿水肿1例。采用Bayes判别函数分析进行统计分析时,仅心室强光点和胎儿水肿可纳入判别分析方程。结果为：正常：Y=0.705＋1.024×心室强光点;Down′s：Y=-54.538＋43.691×心室强光点＋128×胎儿水肿。利用这两个判别函数式可直接计算新检孕妇属于各类的评分,得分最高的一类即该孕妇属于的相应类别。对16例静脉导管血流波形测定的组内变异采用方差分析,无明显统计学差异。结论中期妊娠遗传学超声筛查有利于发现Down′s儿,结合判别分析函数方程可指导是否应该羊水穿刺。     

Increased nuchal translucency in trisomy 13 fetuses at 10–14 weeks of gestation

In a multicenter screening study for trisomy 21 involving ultrasonographic measurement of fetal nuchal translucency thickness (NT) at 10–14 weeks of gestation, 100,311 singleton pregnancies with a live fetus were examined. There were 46 cases of trisomy 13, and in 33 (72%) of these, the NT was above the 95th centile. The estimated risk for trisomy 21, based on maternal age-related risk for this chromosomal abnormality and fetal NT, was above 1 in 300 in 37 (80.1%) of the trisomy 13 fetuses. The fetal crown-rump length was significantly reduced, but the fetal heart rate was increased, being above the 95th centile in 64% of cases. Additionally, 24% of trisomy 13 fetuses had holoprosencephaly and 10% had exomphalos. This study has demonstrated that at 10–14 weeks of gestation, about 80% of fetuses with trisomy 13 can be identified in a screening program for trisomy 21, based on a combination of maternal age and fetal NT. Am. J. Med. Genet. 86:205–207, 1999. © 1999 Wiley-Liss, Inc.