两种不同遗传学分析方法用于诊断自然流产组织的比较

目的探讨比较基因组杂交（CGH）技术与绒毛细胞培养染色体核型分析用于自然流产组织遗传学诊断的准确性。方法选择妊娠49—91d的自然流产患者38例,在无菌条件下经宫颈取绒毛,其中难免流产的新鲜组织标本27份,过期流产的陈旧组织标本11份。每份组织标本均采用绒毛细胞培养染色体核型分析,并同时采用CGH技术对全基因组进行分析。结果CGH技术诊断成功率为100％（38／38）,而绒毛细胞培养染色体核型分析诊断成功率为82％（31／38）。两种方法的诊断符合率为90％（28／31）,在3例出现不同诊断结果的病例中,1例绒毛细胞培养染色体核型分析显示染色体核型正常,而CGH技术显示3q^22_q^24缺失;另2例绒毛细胞培养染色体核型分析为3倍体,但CGH技术诊断结果显示正常。在7例绒毛细胞培养失败而仅有CGH技术诊断结果者中,3例为染色体非整倍体异常,另4例正常。结论CGH技术用于诊断自然流产组织是可行的。绒毛细胞培养染色体核型分析比较,CGH技术诊断成功率高,且对非平衡染色体结构重排的诊断有较高的敏感性,可以作为绒毛细胞培养染色体核型分析的补充方法。     

不同分子遗传学方法用于自然流产绒毛细胞遗传分析的效果

目的 探讨多重连接探针扩增法(MLPA)+荧光原位杂交(FISH)和比较基因组杂交(CGH)+FISH的分子遗传学方法用于自然流产绒毛细胞遗传分析的效果.方法 收集29例自然流产绒毛组织以及6例选择性终止早期妊娠妇女的绒毛组织,采用CGH+FISH、MLPA+FISH方法进行遗传学分析,并与传统的绒毛细胞培养染色体核型分析结果进行比较.结果 MLPA+FISH检测时间为40 h,CGH+FISH检测时问为120 h,绒毛细胞培养染色体核型分析时间为(240±72)h,3者分别比较,差异有统计学意义(P<0.01).CGH、MLPA、FISH和绒毛细胞培养染色体核型分析的标本成功获检率分别为97%(34/35)、100%(35/35)、100%(35/35)和91%(32/35),4者比较,差异无统计学意义(P>0.01).除去CGH获检失败的1份样本外,MLPA+FISH与CGH+FISH的分析结果一致,CGH获检失败的1例标本经MLPA+FISH检测获得了结果.CGH+FISH或MLPA+FISH检测结果与绒毛细胞培养染色体核型分析结果的不一致率分别为13%(4/31)、12%(4/32),两者比较,差异无统计学意义(P>0.05).结论 MLPA+FISH检测耗时短,检测成功率高;MLPA+FISH检测用于自然流产绒毛细胞遗传分析是对绒毛细胞培养染色体核型分析方法的重要补充.     

Comparative genomic hybridization analysis of spontaneous abortion.

OBJECTIVES: To evaluate the feasibility and superiority of comparative genomic hybridization (CGH) in the genetic analysis of spontaneously aborted tissues. METHODS: 38 conceptuses from early failed pregnancies were studied, of which, 27 samples were fresh and 11 were old. Each sample was divided into two parts, one part for conventional cytogenetic analysis and the other for CGH analysis. RESULTS: All 38 spontaneously aborted tissues were analyzed successfully by the CGH approach, but only 31 samples received results from the cytogenetic karyotype analysis, while 7 other tissues failed to get data due to failure in tissue culturing. Among the specimen successfully analyzed by both approaches, 90% (28 out of 31) obtained identical results, and 14 aneuploidies were found. The only structural chromosome aberration in this series, 46, XY, del(3) (q22-24), was found using the CGH approach, which appeared as a normal male karyotype on the chromosomal metaphase spread. Also, two cases indicated triploidies under cytogenetic analysis but appeared to be normal on the CGH profile. In addition, among the seven samples of tissue culture failure, CGH identified three to be aneuploidies. CONCLUSION: The CGH analysis accurately identifies chromosomal unbalanced abnormalities related to spontaneous abortions with low failure rate.     

Detection of numerical chromosome aberrations by comparative genomic hybridization

At least 50 per cent of all first-trimester spontaneous abortions are cytogenetically abnormal, including trisomy, monosomy X, triploidy, tetraploidy and structural chromosome anomalies. Traditionally, the detection of aneuploidy in fetal tissues is performed by tissue sampling, cell culturing, metaphase spread preparation, and conventional banding analyses. This is a tedious, laborious and time-consuming process, prone to errors due to external contamination, culture failure and selective growth of maternal cells. In the present study, we applied the CGH technique in the detection of numerical chromosome abnormalities in 50 placentae of spontaneously aborted fetuses. CGH detected six different types of trisomy (trisomy 8, 15, 16, 18, 22 and 21), one double trisomy (involving chromosomes 14 and 21), and one monosomy X. Overall, nine samples (18 per cent) harboured numerical chromosome aberrations. Aneuploidy was detected in eight samples by CGH and in six samples by conventional cytogenetic analysis. In only one case, CGH failed to detect a mosaic for trisomy revealed by conventional cytogenetic analysis. The successful application of the CGH technique to the detection of aneuploidy in spontaneous abortions, demonstrates the utility of using this technique to screen prenatally for numerical chromosome abnormalities. Our preliminary data support the application of CGH to the clinical genetics setting, at least as a complementary tool to the traditional cytogenetic techniques.     

Cytogenetic analysis of trophoblasts by comparative genomic hybridization in embryo-fetal development anomalies

Cytogenetic studies of spontaneous abortions or intrauterine fetal death depend on conventional tissue culturing and karyotyping. This technique has limitations such as culture failure and selective growth of maternal cells. Fluorescent in situ hybridization (FISH) using specific probes permits diagnosis of aneuploidies but is limited to one or a few chromosomal regions. Comparative genomic hybridization (CGH) provides an overview of chromosomal gains and losses in a single hybridization directly from DNA samples. In a prospective study, we analyzed by CGH trophoblast cells from 21 fetuses in cases of spontaneous abortions, intrauterine fetal death or polymalformed syndrome. Six numerical chromosomal abnormalities including one trisomy 7, one trisomy 10, three trisomies 18, one trisomy 21 and one monosomy X have been correctly identified by CGH. One structural abnormality of the long arm of chromosome 1 has been characterized by CGH. One triploidy and two balanced pericentromeric inversions of chromosome 9 have not been identified by CGH. Sexual chromosomal constitutions were concordant by both classical cytogenetic technique and CGH. Contribution of trophoblast analysis by CGH in embryo-fetal development anomalies is discussed.     

2178对自然流产史夫妇染色体分析

目的:分析自然流产史夫妇外周血染色体异常核型的种类及其在男女性中的分布特点。方法:检测2178对自然流产史夫妇外周血淋巴细胞染色体核型,分析比较染色体变异的种类、发生率及其在男、女性中的分布差异。结果:2178对(4356例)自然流产史夫妇中发现染色体异常539例(12.37%),其中男266例,女273例。染色体结构异常87例,其中相互易位最多见为58例(66.7%,58/87),有27例为世界首报染色体结构异常核型。其次为罗伯逊易位13例,倒位6例,插入、缺失等其他异常核型10例。染色体数目异常8例,包括2例标记染色体、1例XYY及5例不同类型的X染色体非整倍体嵌合。多态性改变444例中,D/G组染色体随体区变异最为多见,共271例(61.04%,271/444)。结论:自然流产史夫妇外周血染色体异常均有发生,男女性发生率并无明显差异,染色体异常以相互易位为主。染色体多态性发生率较高,对以自然流产史就诊的夫妇,有必要同时进行染色体检查,有助于病因的分析与诊断,并为临床咨询及后续生殖干预提供依据。     

Diagnosis of aneuploidy in archival, paraffin-embedded pregnancy-loss tissues by comparative genomic hybridization

OBJECTIVE: To evaluate the detection of aneuploidy in archival tissues from miscarriages by a method that uses microdissection and DNA extraction of villus cells from paraffin blocks, followed by universal DNA amplification and comparative genomic hybridization (CGH). DESIGN: Retrospective analysis. SETTING: Academic medical center. PATIENT(S): Nine archival tissues from cases of spontaneous abortion with trisomy 16 (two cases), trisomy 21 (three cases), trisomy 22 (two cases), triploidy (one case), and monosomy X (one case). INTERVENTION(S): Villus DNA was extracted from microdissected, formalin-fixed, paraffin-embedded tissues. Aneuploidy was detected by CGH after universal amplification of the DNA with the use of degenerate oligonucleotide-primed polymerase chain reaction. MAIN OUTCOME MEASURE(S): Detection of aneuploidy in archival pregnancy-loss tissues using CGH. RESULT(S): In all nine cases, DNA was successfully extracted from the microdissected tissues and was of sufficient quantity and quality for evaluation by CGH. In six of nine cases, the chromosomal abnormality detected by conventional cytogenetic analysis was identified by CGH: trisomy 16 (2/2), trisomy 21 (3/3), and trisomy 22 (1/2). One case of each of the following was not detectable: triploidy (1/1), monosomy X (1/1), and trisomy 22 (1/2). CONCLUSION(S): We propose CGH as a method for determination of aneuploidy in pregnancy-loss archival tissues when conventional cytogenetic analysis is unsuccessful or when it was not performed when fresh tissue was available.     

Karyotype evaluation of repeated abortions in primary and secondary recurrent pregnancy loss

To study the contribution of embryo chromosomal abnormalities in primary and secondary recurrent pregnancy loss (RPL) and to analyze the recurrence of chromosomal constitution in miscarriages from the same couple. Retrospective study of abortion karyotypes in RPL families based on the mother’s primary or secondary RPL status (563 embryo specimens, 335 samples from primary, and 228 samples from secondary RPL). RPL was defined as two or more consecutive miscarriages. One hundred eight cases of recurrent embryo/fetal loss in 51 families were analyzed to assess the probability of having the same karyotype pattern (recurrent normal or recurrent abnormal) in both previous and subsequent pregnancy loss. The karyotypes of abortions were established using standard cytogenetic analysis, as well as interphase fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH). The frequency of aberrations was 43.9% in abortions from primary RPL versus 52.6% in secondary RPL (p = 0.041). Women 35 years of age or older were the main contributors to this difference. The odds ratio of a subsequent abortion having the same karyotype pattern (normal or abnormal) as the previous one was 6.98 (p = 0.0013). The frequency of abnormalities is higher in abortions from the secondary RPL versus primary RPL group, and this difference is due to the relative deficiency of miscarriages with abnormal karyotypes in older women with primary RPL. The probability of having the same karyotype pattern (recurrent normal or recurrent abnormal) in the previous and subsequent abortion is increased significantly compared with chance.     

Is cytogenetic diagnosis of 46,XX karyotype spontaneous abortion specimens erroneous? Fluorescence in situ hybridization as a confirmatory technique

AIM: Performing the standard cytogenetic technique on spontaneous abortion material is still a valuable tool, but finding a normal 46,XX karyotype can confuse investigators and lead to a problem in diagnosis. This is mainly because it is possible for the female or male conceptus to retain contaminating maternal cells. To address this possibility, we used fluorescence in situ hybridization technique (FISH). X (DXZ1: p11.1-q11.1 region) and Y (DYZ3: p11.1-q11.1 region) chromosome alpha-satellite probes were employed to confirm the karyotypes previously diagnosed as 46,XX by our cytogenetic laboratory, or to verify the occurrence of 'Y chromosome component'. METHODS: Besides conventional long-term tissue cultures and G-bands by trypsin using Giemsa (GTG) bandings, FISH analyses were also performed. RESULTS: A total of 134 spontaneous abortion specimens (singleton gestations) were referred for cytogenetic evaluation, of which 125 specimens were successfully karyotyped. Of these, 20.8% (26/125) had chromosome aberrations; 88.5% (23/26) of these aberrations were numerical and 11.5% (3/26) were structural. The most prevalent numerical anomalies were trisomies 15, 16 and 21, tetraploidies, triploidies and monosomy X. FISH results were obtained for 45 out of 92 cases with 46,XX, of which 2 (4.4%) showed XY signals. CONCLUSIONS: For accurate cytogenetic evaluation of spontaneous abortion materials, an additional technique such as FISH is required in order to confirm the cytogenetic results or to provide an estimate of the error rate in the analysis of miscarriages.     

先天性疾病研究及产前诊断中Array CGH的应用

染色体微缺失、重复、扩增和非整倍体等基因组DNA失衡是导致胎儿发育迟缓、畸形、死胎、流产和其他先天性疾病的内在原因。微阵列－比较基因组杂交技术（Array CGH）利用基因芯片取代了传统比较基因组杂交技术的正常中期染色体作为杂交靶标,与分别采用不同荧光标记的待测DNA和参照DNA杂交,通过比较两种荧光强度的比率,检测出染色体基因拷贝数变化。Array CGH已成为一个重要的细胞遗传学研究工具,用于产前诊断和先天性疾病诊断染色体亚显微结构异常。     

1437例早孕期自然流产胚胎核型分析

目的:分析早孕期自然流产胚胎的异常核型的发生率。方法:对自然流产刮宫术后取得的胚胎绒毛细胞进行体外培养,G显带核型分析,统计异常核型的分布情况。结果:共收集到1 437例标本,患者平均年龄31.2±4.4岁,平均妊娠时间66.5±14.1 d。培养成功1 390例(96.73%),失败47例(3.27%)。正常核型595例(42.81%);异常核型795例(57.20%),其中非整倍体571例(71.82%)。前5位非整倍体排序为:16-三体(21.54%);22-三体(15.41%);45,X(14.01%);15-三体(4.38%);13-三体(4.20%)。染色体结构异常(包括不平衡易位、罗氏不平衡、缺失、插入、倒位、标记染色体等)比例较低,占自然流产总量的3.52%,占异常核型的6.16%。按患者年龄分为35岁组和≥35岁组,异常核型检出率分别为55.30%和63.69%,组间有统计学差异(P=0.008);非整倍体率分别为68.74%和81.00%,组间有统计学差异(P=0.001)。而嵌合体、三倍体、四倍体发生率无统计学差异。染色体结构异常发生率35岁组为8.07%,显著高于≥35岁组(0.50%)(P0.001)。第1次、第2次及≥3次自然流产异常核型发生率分别为61.64%、55.44%、52.62%,组间有统计学差异(P0.05)。结论:胚胎核型异常是早孕期自然流产的主要原因,非整倍体是主要异常核型。高龄孕妇异常核型与非整倍体发生率增高,染色体结构异常发生率降低。随自然流产次数增加,胎儿异常核型比例呈下降趋势;这说明流产次数本身是自然流产的风险之一。     

Cytogenetic study in 50 couples with recurrent abortions

The presence of chromosome abnormalities in couples with repeated spontaneous abortion is known even if the phenomenon is far from a complete assessment. A cytogenetic investigation in 50 couples with a history of two or more spontaneous abortions is referred to in this study. A peripheral blood lymphocyte culture was harvested for each subject and the slides were stained by G- and C-banding. Of the 100 individuals examined, 4 were carriers of balanced translocations, 3 of which were of the Robertsonian type. A chromosomal fragility (chromatidic and/or chromosomic gaps) was seen in 2 cases. The incidence of balanced translocations found here is 8% which is near to the mode (about 9%) observed in previous studies. Those frequencies are greater than in the general population (0.1-0.4%). This indicates that balanced translocations have some importance in causing abortion while this is not the case for other chromosomal abnormalities (e.g. pericentric inversions). Thus, cytogenetic analyses should be recommended in couples with repeated spontaneous abortions, when clinical data fail to clarify the cause.     

Detecting sex chromosome anomalies and common triploidies in products of conception by array-based comparative genomic hybridization

OBJECTIVES: In recent years, array-based comparative genomic hybridization (array CGH) has moved to the forefront of molecular cytogenetics with its ability to rapidly characterize chromosome abnormalities at resolutions much higher than routine chromosome banding. However, array CGH, like all CGH procedures, has heretofore been deemed unable to detect ploidy, a major cause of fetal demise and spontaneous miscarriage. METHOD: We recently developed a CGH microarray that is designed for detecting aneuploidy and unbalanced chromosome rearrangements. Here, we introduce the use of a Klinefelter male cell line (47,XXY) as a control for array CGH analyses on products of conception (POCs). RESULTS: This approach facilitates the detection of common trisomies and monosomies of the sex chromosomes by reducing the analysis to the identification of single copy gains or losses. Furthermore, in a blinded study, careful interpretation of the microarray results with particular attention to the sex chromosome ratios between the patient sample and the control allowed for the detection of some common triploidies. CONCLUSION: These results suggest that using a chromosomally abnormal cell line in array CGH analysis can be applied to other CGH platforms and that array CGH, when properly performed and analyzed, is a powerful tool that can detect most chromosomal abnormalities observed in a clinical setting including some polyploidies.     

Molecular cytogenetic characterisation of an interstitial deletion 12p detected by prenatal diagnosis

OBJECTIVES: Deletions in the short arm of chromosome 12 are rare structural aberrations. Till now only ten patients with interstitial deletions are described in the literature. Here, we report on the first case detected by prenatal diagnosis. Chorionic villi sampling was performed in the 14th week of gestation, indicated by fetal abnormalities detected by ultrasound examination. Conventional cytogenetic and molecular cytogenetic techniques were applied to determine the correct karyotype of the affected fetus. RESULTS: Analysing Giemsa- and QFQ-stained chromosomes of the CVS short-term culture, a structural aberrant chromosome 12 was detected. Fluorescence in situ hybridisation with YAC-probes and CGH analysis with DNA extracted from native chorionic villi proved an interstitial deletion in the aberrant chromosome 12. The GTG-banded chromosomes of the CVS long-term culture confirmed these results. Analyses of the parental chromosomal sets yielded normal results, indicating a de novo aberration. Array CGH analysis was performed to determine accurately the deletion breakpoints. Finally, according to ISCN 2005, the karyotype could be determined as 46,XX.arr cgh 12p13.2p11.21(RP11-77I22-->RP11-144O23)x 1. CONCLUSION: The presented case shows the power of modern cytogenetic methods, allowing a more detailed diagnosis in affected individuals, and therefore, facilitating a more reliable prenatal diagnosis.     

复苏囊胚移植妊娠自然流产原因分析

目的:探讨冷冻复苏囊胚移植妊娠中自然流产的原因。方法:回顾性分析冷冻复苏囊胚移植妊娠病例108例,根据是否自然流产分为流产组(n=20)和继续妊娠组(n=88),应用Logistic回归分析可能影响妊娠结局的因素,并且分析了部分流产病例的胚胎染色体结果。结果:复苏囊胚移植总自然流产率为18.50%(20/108),早期自然流产率为16.67%(18/108),早期流产占总流产的90%(18/20)。流产组年龄大于继续妊娠组(33.3±4.0岁vs31.0±3.6岁,P=0.02),10例染色体检查结果中7例为异常染色体,非整倍体是常见的异常核型。结论:染色体异常可能是冷冻复苏囊胚移植妊娠中自然流产的最常见原因,流产与年龄增大有关。     

Benefit of an anatomo-pathological examination performed on the product of conception in early spontaneous abortion

The examination of the product of conception after spontaneous abortion reveals that in about 60% of cases a chromosome abnormality is present, and that in only 1% of cases the abnormality is transmitted by parents. This survey deals with 381 cases of spontaneous abortion, and 670 cases of abortion induced for psychological or socioeconomical reasons, and with the cytogenetic examination of the aborted materials to study the anatomo-pathological modifications of the embryo. 29.23% of the embryos examined in the first series presented chromosome abnormalities, ranging, in decreasing order, from trisomies, to triploidies, to monosomies, compared to only 1.93% in the second series. It must be noted that this kind of examination often presents serious difficulties of interpretation.     

非多态性位点多重荧光定量PCR技术在产前诊断胎儿染色体非整倍体异常中的应用

目的 探讨非多态性位点多重荧光定量PCR(QF.PCR)技术快速产前诊断胎儿染色体非整倍体异常的可行性.方法 2006年3月至2007年11月间,收集南京大学医学院附属鼓楼医院早孕期自然流产绒毛组织、中孕期羊水及妊娠晚期的胎儿脐血共63例为研究组.同期60例健康成年人外周血标本(男、女性各30例)作为正常对照组.采用非多态性位点QF-PCR技术检测两组各样本的染色体非整倍体异常情况,以人釉原蛋白基因(AMXY)位点为内参照,根据公式计算剂量系数(DQ)值,DQ值在0.7～1.3之间为正常,>1.3为染色体扩增,<0.7则为染色体存在缺失.当2个以上位点电泳峰与AMXY比值异常时,为性染色体数目异常,即各位点与性染色体峰面积比值均>2.0或<0.7.将QF-PCR的检测结果与染色体核型分析结果进行比较.结果 (1)正常对照组中女性性染色体检测结果为AMX,男性性染色体检测结果为AMX、AMY,与染色体核型分析结果一致.各常染色体DQ值的均值为0.7～1.3,标准差为0.05～0.12.(2)研究组63例中有19例为染色体非整倍体异常,其中13例与核型分析结果一致.与核型分析结果不一致的6例中,1例在18q22.3的CNDP2基因位点表现为三体改变,位于18q12.1的CDH2基因位点表现为正常二倍体,其DQ值为1.28,染色体核型分析为47,XY,+18;5例非多态性位点QF-PCR结果提示有染色体拷贝数异常,而核型分析结果未见异常,其中1例为47,XY,+13,核型分析结果为46,XX;1例为Y染色体缺失,而核型分析结果为46,XY;另外3例中1例为47,XX,+16,2例为47,XX,+13,而核型分析结果均为46,XX.(3)研究组63例中有44例染色体为正常二倍体,其中36例(82%)与核型分析结果一致.与核型分析结果不一致的8例中,1例为培养失败;2例非多态性QF-PCR结果为正常男性,而核型分析结果为正常女性;4例核型分析为多倍体,其中3例核型分析为69,XXX,1例核型分析为92.XXXX;1例核型分析为45,XX,rob(13;21).结论 采用非多态性位点QF-PCR技术进行产前诊断胎儿染色体非整倍体畸形,具有通量高、快速、价廉等特点,有较好的临床应用价值.     

Genetic factors of recurrent abortions

A review of main genetic factors involved in pathogenesis of recurrent abortion is presented. The prevalence of chromosomal abnormalities in spontaneous abortions and the role of parental abnormalities of karyotype is pointed out, also in relation to many recent studies. The result of 354 karyotypes performed on couples with spontaneous abortion are presented; the prevalence of chromosomal abnormalities resulted 4.2%, with 73% of translocations, either reciprocal (40%) or robertsonian (33%), and 27% of inversions. The low number of minor abnormalities (0.8%) seems to confirm their poor clinical significance.     

Outcome of cystic hygroma in fetuses with normal karyotypes depends on associated findings

OBJECTIVE: To determine the associated diagnostic findings which are linked with adverse fetal outcome in nuchal cystic hygroma. STUDY DESIGN: Based on a series of 32 cases, we determined the sonographic morphology of the hygroma, associated structural anomalies, karyotypes and autopsy findings. Intrauterine fetal death, spontaneous abortion and abnormal karyotypes were assigned as adverse outcome parameters. RESULTS: The mean gestational age at diagnosis was 14.4 weeks (range 10-21). There were 18 nonseptated and 14 septated hygromas. Besides hygroma, associated sonographic detectable structural anomalies were observed in 17 cases (53.1%). The greatest number of associated sonographic anomalies were hydrops (31.3%), generalised skin oedema (6.3%) and pterygium colli (6.3%). Cytogenetic analysis revealed an abnormal karyotype in 13 of 26 (50%) invasive procedures. Turner syndrome and Trisomy 18 (both 15.4%) were the most frequent cytogenetic abnormalities. Autopsy was performed in 24 cases and 16 cases (66.7%) had an associated autopsy finding to hygroma colli. The most frequent associated autopsy findings were limb and craniofacial anomalies (both 25%). Only 3 (9.4%) mothers gave birth to healthy newborns. The overall fetal adverse outcome rate was 68.8% (22 cases). CONCLUSIONS: Fetuses with NCH are at high risk for adverse outcome and detailed prenatal diagnosis including invasive procedures should be offered. According to the presented autopsy findings, to determine fetal outcome in NCH cases with normal karyotypes, detailed sonography should be concentrated beside the exclusion of fetal heart defects and existence of hydrops fetalis, on the skeletal, urogenital and craniofacial anomalies, as these might cause severe morbidity.     

Prenatal detection of cardiovascular malformations by echocardiography: an indication for cytogenetic evaluation

Prenatal diagnosis of congenital cardiovascular malformations by echocardiography may signal associated chromosome abnormalities. The exact proportion of these associations is not known but is expected to be higher than that with live-birth. To estimate the risk that a fetus with an echocardiographically detected heart defect has an autosomal trisomy or Turner syndrome, we adjusted the known frequency of aneuploidy in live-born infants with congenital cardiovascular malformations by the reported rate of spontaneous abortion, with data from a population-based case-control study of congenital cardiovascular malformations in which 268 cases (12.7%) had both congenital cardiovascular malformations and a chromosome abnormality. Included in the present analysis were 188 aneuploid infants with congenital cardiovascular malformations that would have been detectable by fetal echo. When data are adjusted for the high spontaneous abortion rate of aneuploid fetuses, we estimate that there would have been more than a threefold increase in aneuploidy over the 13% seen at live-birth. Thus cytogenetic analysis is appropriate in a fetus with echo-diagnosed congenital cardiovascular malformations.