Cytological and epidemiological findings in trisomies 13, 18, and 21: England and Wales 2004-2009

This study describes the cytological and epidemiological findings in 985 trisomy 13 and 2512 trisomy 18 compared with 10,255 trisomy 21 diagnoses between 2004 and 2009 included in the National Down Syndrome Cytogenetic Register of England and Wales. The frequency of occurrence, proportions diagnosed prenatally, sex ratios, mean maternal age, and proportions of mothers with recurrences were analyzed. Ninety-seven, 98%, and 92% were free karyotypes for trisomy 21, 18, and 13, respectively; 3% of 21, 1% of 18, and 8% of trisomy 13 were translocations; and under 1% of trisomies 21 and 18 were double or triple aneuploids. Overall 1% of each trisomy had mosaicism, but 48% of the trisomy 21 double aneuploids, and 10% of trisomy 18 multiple aneuploids had mosaicism. The proportion of livebirths was 40% of trisomy 21, 11% of 18, and 13% of 13, respectively. Free trisomies 21 and 13 had an excess of males, and 18 had an excess of females, as did mosaic free trisomies 21 and 18. Mean maternal ages were 35.9 years in trisomy 21, 36.4 years in 18, and 34.6 years in 13. During the 6 years of data collection 1% of the mothers had recurrences, most recurrent trisomy 21 or 18 were identical translocations, but hetero-trisomic recurrences included 21 and 18, and 21 and 13. There are significant differences between the trisomic karyotypes and attributes, possibly related to their variable origins. Notable are the relative excess of trisomy 13 translocations, mosaicism in cases with multiple aneuploidy, and the types of homo- and hetero-recurrences.     

Systematic evidence-based review: The application of noninvasive prenatal screening using cell-free DNA in general-risk pregnancies

PurposeNoninvasive prenatal screening (NIPS) using cell-free DNA has been assimilated into prenatal care. Prior studies examined clinical validity and technical performance in high-risk populations. This systematic evidence review evaluates NIPS performance in a general-risk population.MethodsMedline (PubMed) and Embase were used to identify studies examining detection of Down syndrome (T21), trisomy 18 (T18), trisomy 13 (T13), sex chromosome aneuploidies, rare autosomal trisomies, copy number variants, and maternal conditions, as well as studies assessing the psychological impact of NIPS and the rate of subsequent diagnostic testing. Random-effects meta-analyses were used to calculate pooled estimates of NIPS performance (P < .05). Heterogeneity was investigated through subgroup analyses. Risk of bias was assessed.ResultsA total of 87 studies met inclusion criteria. Diagnostic odds ratios were significant (P < .0001) for T21, T18, and T13 for singleton and twin pregnancies. NIPS was accurate (≥99.78%) in detecting sex chromosome aneuploidies. Performance for rare autosomal trisomies and copy number variants was variable. Use of NIPS reduced diagnostic tests by 31% to 79%. Conclusions regarding psychosocial outcomes could not be drawn owing to lack of data. Identification of maternal conditions was rare.ConclusionNIPS is a highly accurate screening method for T21, T18, and T13 in both singleton and twin pregnancies.     

Noninvasive prenatal screening (NIPS) for fetal chromosome abnormalities in a general-risk population: An evidence-based clinical guideline of the American College of Medical Genetics and Genomics (ACMG)

PurposeThis workgroup aimed to develop an evidence-based clinical practice guideline for the use of noninvasive prenatal screening (NIPS) for pregnant individuals at general risk for fetal trisomy 21, trisomy 18, or trisomy 13 and to evaluate the utility of NIPS for other chromosomal disorders.MethodsThe NIPS Evidence-Based Guideline Work Group (n = 7) relied on the results from the recent American College of Medical Genetics and Genomics (ACMG) systematic review to form the evidentiary basis of this guideline. Workgroup members used the Grading of Recommendations Assessment, Development, and Evaluation Evidence to Decision framework to draft recommendations. The guideline underwent extensive internal and external peer review with a public comment period before approval by the ACMG Board of Directors.ResultsEvidence consistently demonstrated improved accuracy of NIPS compared with traditional screening methods for trisomies 21, 18, and 13 in singleton and twin gestations. Identification of rare autosomal trisomies and other microdeletion syndromes with NIPS is an emerging area of interest.ConclusionACMG strongly recommends NIPS over traditional screening methods for all pregnant patients with singleton and twin gestations for fetal trisomies 21, 18, and 13 and strongly recommends NIPS be offered to patients to screen for fetal sex chromosome aneuploidy.     

A cytogenetic register of trisomies in Scotland: results of the first 2 years (1989, 1990)

A population-based register of all autosomal trisomies diagnosed in Scotland was established in 1989. Data were provided by all cytogenetic service laboratories, and included karyotype, date and place of outcome, indication for analysis, maternal age and place of residence. The Register includes all foetuses diagnosed prenatally and all cytogenetically-confirmed live- and still-births with autosomal trisomy, including partial, mosaic and familial cases. In the 2 years 1989-90, 76 prenatal and 147 postnatal diagnoses were notified. For Down syndrome karyotypes the estimated rate, assuming no terminations and after adjusting for spontaneous foetal losses following diagnosis, was 1.23 per 1000 livebirths. This was almost identical to that expected by applying published maternal age-specific rates to the maternal age distribution in Scotland, indicating a very high level of ascertainment. The adjusted rates for trisomies 13 and 18 were also close to expected values derived from published data. Prenatal screening was estimated to reduce the newborn incidence of trisomy 21 by about one quarter overall, and about one half in mothers over 35 years. For trisomy 18, the estimated overall reduction was also about one quarter. It is concluded that the Register provides a practical and cost-effective means of monitoring the effects of prenatal screening, with near-complete ascertainment. In the longer term it will provide a database for studies of the actiology of these conditions.     

Trisomies 13 and 18: population prevalences, characteristics, and prenatal diagnosis, metropolitan Atlanta, 1994-2003

In recent years, prenatal diagnosis and elective pregnancy termination have affected the reported birth prevalence of trisomies 13 and 18. We examined the prevalence and characteristics of these conditions using 1994-2003 data from a population-based surveillance system, the Metropolitan Atlanta Congenital Defects Program. Including fetal deaths and elective terminations increased the number of affected pregnancies by 58.7% for trisomy 13 and 72.2% for trisomy 18. Prenatal cytogenetic testing was reported in 70.8% of trisomy 13 cases and 76.1% of trisomy 18 cases. Among those with prenatal cytogenetic tests, 60.8% of trisomy 13 and 59.7% of trisomy 18 cases were electively terminated. Compared with non-Hispanic whites, non-Hispanic black race was associated with a decreased frequency of prenatal cytogenetic testing for both trisomy 13 and trisomy 18 (OR 0.24, 95% CI: 0.08-0.78 and OR 0.32, 95% CI: 0.14-0.69, respectively). The reported rates of prenatal cytogenetic testing remained stable throughout the period. As expected, maternal age > or =35 years was a risk factor for both conditions. However, while 67.1% (n = 55) of the trisomy 18 case mothers were > or =35 years, only 46.9% (n = 15) of the trisomy 13 case mothers were > or =35 years. Among live-born infants, the sex ratio among trisomy 18 infants showed an increased proportion of females: 60.4% female versus 39.6% male. However, the proportion was 48.3% female and 51.7% male among fetuses that were electively terminated in the second trimester. Inclusion of pregnancies that are prenatally diagnosed is critical for accurate surveillance and population-based analyses of these conditions.     

无创性产前基因测序技术在染色体非整倍体中的应用

目的探讨高通量并行测序技术在胎儿染色体非整倍体检测中的应用价值。方法2012年10月至2013年4月,生化血清学筛查唐氏高危或高龄孕妇,采用高通量测序技术对胎儿染色体非整倍体进行无创性产前检测,评估患病风险率,提示高危孕妇进行核型分析确诊。结果813例无创检测高危孕妇,13例提示异常高危,异常率为1．59％,其中4例21三体,3例18三体,6例性染色体。核型确诊4例均为21三体,准确度100％;2例18三体;1例47,XXY和1例47,XXX。结论基于高通量测序技术的方法能快速、准确、无创检测唐氏综合征,相对18三体和性染色体检测准确度和稳定性有待优化与提高。     

Outcome of publicly funded nationwide first-tier noninvasive prenatal screening

PurposeNoninvasive prenatal screening (NIPS) using cell-free DNA has transformed prenatal care. Belgium was the first country to implement and fully reimburse NIPS as a first-tier screening test offered to all pregnant women. A consortium consisting of all Belgian genetic centers report the outcome of two years genome-wide NIPS implementation.MethodsThe performance for the common trisomies and for secondary findings was evaluated based on 153,575 genome-wide NIP tests. Furthermore, the evolution of the number of invasive tests and the incidence of Down syndrome live births was registered.ResultsTrisomies 21, 18, and 13 were detected in respectively 0.32%, 0.07%, and 0.06% of cases, with overall positive predictive values (PPVs) of 92.4%, 84.6%, and 43.9%. Rare autosomal trisomies and fetal segmental imbalances were detected in respectively 0.23% and 0.07% of cases with PPVs of 4.1% and 47%. The number of invasive obstetric procedures decreased by 52%. The number of trisomy 21 live births dropped to 0.04%.ConclusionExpanding the scope of NIPS beyond trisomy 21 fetal screening allows the implementation of personalized genomic medicine for the obstetric population. This genome-wide NIPS approach has been embedded successfully in prenatal genetic care in Belgium and might serve as a framework for other countries offering NIPS.     

Autosomal trisomy and maternal use of multivitamin supplements

Recent reports suggest that women carrying certain polymorphisms of folate genes associated with suboptimal folate status might be at increased risk for having a child with Down syndrome or other autosomal trisomies, and hypothesized that maternal use of multivitamin supplements might reduce such risk. To evaluate this hypothesis, we examined data from a population-based case-control study, and contrasted cases of Down syndrome, trisomy 18, and trisomy 13, with unaffected controls. Periconceptional multivitamin use, compared to no such use, was associated with an odds ratio (OR) of 0.9 (95% confidence interval [CI], 0.6-1.3) for having a pregnancy affected by an autosomal trisomy. The OR was 0.8 (95% CI, 0.5-1.3) for Down syndrome and 1.4 (95% CI, 0.5-3.6) for trisomies 13 and 18, with little variation by maternal race or age. Periconceptional multivitamin use was not associated with a major reduction in the risk for common autosomal trisomies.     

Noninvasive prenatal testing using a novel analysis pipeline to screen for all autosomal fetal aneuploidies improves pregnancy management

Noninvasive prenatal testing by massive parallel sequencing of maternal plasma DNA has rapidly been adopted as a mainstream method for detection of fetal trisomy 21, 18 and 13. Despite the relative high accuracy of current NIPT testing, a substantial number of false-positive and false-negative test results remain. Here, we present an analysis pipeline, which addresses some of the technical as well as the biologically derived causes of error. Most importantly, it differentiates high z-scores due to fetal trisomies from those due to local maternal CNVs causing false positives. This pipeline was retrospectively validated for trisomy 18 and 21 detection on 296 samples demonstrating a sensitivity and specificity of 100%, and applied prospectively to 1350 pregnant women in the clinical diagnostic setting with a result reported in 99.9% of cases. In addition, values indicative for trisomy were observed two times for chromosome 7 and once each for chromosomes 15 and 16, and once for a segmental trisomy 18. Two of the trisomies were confirmed to be mosaic, one of which contained a uniparental disomy cell line. As placental trisomies pose a risk for low-grade fetal mosaicism as well as uniparental disomy, genome-wide noninvasive aneuploidy detection is improving prenatal management.     

Performance of prenatal screening by non-invasive cell-free fetal DNA testing for women with various indicationsCSCD

Objective: To assess the performance of non-invasive prenatal testing (NIPT) based on massive parallel sequencing. Methods: A total of 10 275 maternal blood samples were collected. Fetal chromosomal aneuploides were subjected to low coverage whole genome sequencing. Patients with high risks received further prenatal diagnosis. The outcome of all patients were followed up. Results: High-throughput sequencing detected 72 pregnancies with fetal autosomal chromosomal aneuploidy, including 57 cases of trisomy 21, 14 cases of trisomy 18, and 1 case of trisomy 13. The positive predictive value for trisomies 21 and 18 were 98.25% and 91.67%, respectively. Comparing its performance in intermediate or high risk pregnancies, advanced maternal age pregnancies and volunteering to test pregnancies, the positive predictive value were 100%, 95%, 90% and 50%, respectively. The follow up result was only 1 case of 21 trisomy false negative with high risk. For the 56 cases of trisomy 21, the high risk group accounted for 55%, advanced maternal age accounted for 29%, the intermediate risk referred to 14%, the volunteering to test group accounted for 2%. Conclusion: The performance of NIPT for trisomies 21, 18 and 13 was satisfactory. The method can be used for women with advanced gestational age. NIPT has offered an ideal secondary screening method for those with an intermediate or high risk, and can reduce the rate of birth defects. © 2018 West China University of Medical Sciences. All rights reserved.     

无创DNA产前检测在诊断胎儿染色体非整倍体疾病中的应用

目的探讨新一代测序技术的无创DNA产前检测在诊断胎儿染色体非整倍体疾病中的应用价值。方法 2012年8月1日至2013年12月31日在辽宁省大连市妇幼保健院接受孕妇外周血中游离胎儿DNA检测者2548例,均为单胎,妊娠12周-26周,按照孕妇年龄、血清学筛查结果及超声检测结果分为唐氏综合征筛查（唐筛）高危组、高龄组（孕产期年龄超过35周岁）、B超检测异常组和其他原因组,共计4组,由北京贝瑞和康生物技术有限公司和湖南家辉遗传专科医院合作开展的＂大规模基于新一代测序技术的新型无创DNA产前检测＂对孕妇外周血中游离胎儿DNA进行序列分析,对检测结果阳性者进行羊水穿刺或脐血穿刺及胎儿染色体核型分析;对检测结果阴性者行电话随访其胎儿出生后情况。结果 ①4组孕妇共计2548例均成功完成游离胎儿DNA检测,检测结果为阳性者共39例,包括21三体18例、18三体7例、13三体2例、性染色体异常12例。其中唐筛高危组检出21三体5例、18三体1例、13三体0例、性染色体异常3例;高龄组检出21三体3例、18三体3例、13三体0例、性染色体异常5例;B超检测异常组检出21三体9例、18三体2例、13三体0例、性染色体异常2例;其他原因组检出21三体1例、18三体1例、13三体2例、性染色体异常2例;②孕妇游离胎儿DNA检测结果异常的39例孕妇中,32例进行了羊水穿刺或脐血穿刺及染色体核型分析。18例21三体检测阳性者中,13例进行了羊水穿刺或脐血穿刺,其中12例结果与无创DNA吻合,1例不吻合,5例拒绝羊水穿刺或脐血穿刺而直接引产,经随访胎儿均有异常。结果检出率100%,准确率92.3%。7例18三体检测阳性者中,有6例进行了羊水穿刺或脐血穿刺,其中5例结果与无创DNA吻合,1例不吻合,1例拒绝羊水穿刺或脐血穿刺而直接引产,经随访胎儿存在多处异常。结果检出率100%,准确率83.3%。2例13三体检?     

Twenty-year trends in the prevalence of Down syndrome and other trisomies in Europe: impact of maternal age and prenatal screening

This study examines trends and geographical differences in total and live birth prevalence of trisomies 21, 18 and 13 with regard to increasing maternal age and prenatal diagnosis in Europe. Twenty-one population-based EUROCAT registries covering 6.1 million births between 1990 and 2009 participated. Trisomy cases included live births, fetal deaths from 20 weeks gestational age and terminations of pregnancy for fetal anomaly. We present correction to 20 weeks gestational age (ie, correcting early terminations for the probability of fetal survival to 20 weeks) to allow for artefactual screening-related differences in total prevalence. Poisson regression was used. The proportion of births in the population to mothers aged 35+ years in the participating registries increased from 13% in 1990 to 19% in 2009. Total prevalence per 10 000 births was 22.0 (95% CI 21.7–22.4) for trisomy 21, 5.0 (95% CI 4.8–5.1) for trisomy 18 and 2.0 (95% CI 1.9–2.2) for trisomy 13; live birth prevalence was 11.2 (95% CI 10.9–11.5) for trisomy 21, 1.04 (95% CI 0.96–1.12) for trisomy 18 and 0.48 (95% CI 0.43–0.54) for trisomy 13. There was an increase in total and total corrected prevalence of all three trisomies over time, mainly explained by increasing maternal age. Live birth prevalence remained stable over time. For trisomy 21, there was a three-fold variation in live birth prevalence between countries. The rise in maternal age has led to an increase in the number of trisomy-affected pregnancies in Europe. Live birth prevalence has remained stable overall. Differences in prenatal screening and termination between countries lead to wide variation in live birth prevalence.     

Microarray comparative genomic hybridization (CGH)-based prenatal diagnosis for chromosome abnormalities using cell-free fetal DNA in amniotic fluid

Cell-free fetal DNA (cffDNA) in the supernatant of amniotic fluid, which is usually discarded, can be used as a sample for prenatal diagnosis. For rapid prenatal diagnosis of frequent chromosome abnormalities, for example trisomies 13, 18, and 21, and monosomy X, using cffDNA, we have developed a targeted microarray-based comparative genomic hybridization (CGH) panel on which BAC clones from chromosomes 13, 18, 21, X, and Y were spotted. Microarray-CGH analysis was performed for a total of 13 fetuses with congenital anomalies using cffDNA from their uncultured amniotic fluid. Microarray CGH with cffDNA led to successful molecular karyotyping for 12 of 13 fetuses within 5 days. Karyotypes of the 12 fetuses (one case of trisomy 13, two of trisomy 18, two of trisomy 21, one of monosomy X, and six of normal karyotype) were later confirmed by conventional chromosome analysis using cultured amniocytes. The one fetus whose molecular-karyotype was indicated as normal by microarray CGH actually had a balanced translocation, 45,XY,der(14;21)(q10;q10). The results indicated that microarray CGH with cffDNA is a useful rapid prenatal diagnostic method at late gestation for chromosome abnormalities with copy-number changes, especially when combined with conventional karyotyping of cultured amniocytes.     

Investigation of maternal blood enriched for fetal cells: role in screening and diagnosis of fetal trisomies.

Prenatal diagnosis of chromosomal abnormalities relies on assessment of risk followed by invasive testing in the group with highest risk. Assessment of risk by a combination of maternal age and fetal nuchal translucency and invasive testing in the 5% of the population with the highest risk would identify about 80% of trisomy 21 pregnancies. Preliminary reports suggest that chromosomal abnormalities can also be diagnosed by fluorescent in situ hybridization (FISH) in maternal blood enriched for fetal cells. This study examines the potential role of this method on the prenatal diagnosis of fetal trisomies. Maternal blood was obtained before invasive testing in 230 pregnancies at 10-14 weeks of gestation. After enrichment for fetal cells, by triple density centrifugation and anti-CD71 magnetic cell sorting, FISH was performed and the proportion of cells with positive signals in the chromosomally normal and abnormal groups was determined. Fetal karyotype was normal in 150 cases and abnormal in 80 cases, including 36 with trisomy 21. Using a 21 chromosome-specific probe, three-signal nuclei were present in at least 5% of the enriched cells from 61% of the trisomy 21 pregnancies and in none of the normal pregnancies. For a cut-off of 3% of three-signal nuclei the sensitivity for trisomy 21 was 97% for a false positive rate of 13%. Similar values were obtained in trisomies 18 and 13 using the appropriate chromosome-specific probe. Examination of fetal cells from maternal blood may provide a noninvasive prenatal diagnostic test for trisomy 21 with the potential of identifying about 60% of affected pregnancies. Alternatively, this technique can be combined with maternal age and fetal nuchal translucency as a method of selecting the high-risk group for invasive testing. Potentially, 80% of trisomy 21 pregnancies could be identified after invasive testing in less than 1% of the pregnant population.     

Investigation of maternal blood enriched for fetal cells: Role in screening and diagnosis of fetal trisomies

Prenatal diagnosis of chromosomal abnormalities relies on assessment of risk followed by invasive testing in the group with highest risk. Assessment of risk by a combination of maternal age and fetal nuchal translucency and invasive testing in the 5% of the population with the highest risk would identify about 80% of trisomy 21 pregnancies. Preliminary reports suggest that chromosomal abnormalities can also be diagnosed by fluorescent in situ hybridization (FISH) in maternal blood enriched for fetal cells. This study examines the potential role of this method on the prenatal diagnosis of fetal trisomies. Maternal blood was obtained before invasive testing in 230 pregnancies at 10–14 weeks of gestation. After enrichment for fetal cells, by triple density centrifugation and anti-CD71 magnetic cell sorting, FISH was performed and the proportion of cells with positive signals in the chromosomally normal and abnormal groups was determined. Fetal karyotype was normal in 150 cases and abnormal in 80 cases, including 36 with trisomy 21. Using a 21 chromosome-specific probe, three-signal nuclei were present in at least 5% of the enriched cells from 61% of the trisomy 21 pregnancies and in none of the normal pregnancies. For a cut-off of 3% of three-signal nuclei the sensitivity for trisomy 21 was 97% for a false positive rate of 13%. Similar values were obtained in trisomies 18 and 13 using the appropriate chromosome-specific probe. Examination of fetal cells from maternal blood may provide a noninvasive prenatal diagnostic test for trisomy 21 with the potential of identifying about 60% of affected pregnancies. Alternatively, this technique can be combined with maternal age and fetal nuchal translucency as a method of selecting the high-risk group for invasive testing. Potentially, 80% of trisomy 21 pregnancies could be identified after invasive testing in less than 1% of the pregnant population. Am. J. Med. Genet. 85:66–75, 1999. © 1999 Wiley-Liss, Inc.     

Sex chromosome trisomies in Europe: prevalence, prenatal detection and outcome of pregnancy

This study aims to assess prevalence and pregnancy outcome for sex chromosome trisomies (SCTs) diagnosed prenatally or in the first year of life. Data held by the European Surveillance of Congenital Anomalies (EUROCAT) database on SCT cases delivered 2000–2005 from 19 population-based registries in 11 European countries covering 2.5 million births were analysed. Cases included were livebirths diagnosed to 1 year of age, fetal deaths from 20 weeks gestation and terminations of pregnancy for fetal anomaly (TOPFA). In all, 465 cases of SCT were diagnosed between 2000 and 2005, a prevalence of 1.88 per 10,000 births (95% CI 1.71–2.06). Prevalence of XXX, XXY and XYY were 0.54 (95% CI 0.46–0.64), 1.04 (95% CI 0.92–1.17) and 0.30 (95% CI 0.24–0.38), respectively. In all, 415 (89%) were prenatally diagnosed and 151 (36%) of these resulted in TOPFA. There was wide country variation in prevalence (0.19–5.36 per 1000), proportion prenatally diagnosed (50–100%) and proportion of prenatally diagnosed resulting in TOPFA (13–67%). Prevalence of prenatally diagnosed cases was higher in countries with high prenatal detection rates of Down syndrome. The EUROCAT prevalence rate for SCTs diagnosed prenatally or up to 1 year of age represents 12% of the prevalence expected from cytogenetic studies of newborn babies, as the majority of cases are never diagnosed or are diagnosed later in life. There is a wide variation between European countries in prevalence, prenatal detection and TOPFA proportions, related to differences in screening policies as well as organizational and cultural factors.     

母血清筛查21三体、18三体阳性病例的产前诊断

目的探讨孕中期母血清筛查21-三体，18-三体阳性病例的染色体异常情况。方法AFP和Free-heG13用美国PE公司的时间分辨免疫荧光分析系统测定，风险值计算21-三体以1／270，18-三体以1／350为切割值。阳性病例进行羊膜腔穿刺羊水细胞培养。结果在54580例产前筛中有2615例为21-三体或18-三体阳性病例，占总筛查人数的4．79％。其中对1161例阳性病例进行了染色体分析（占总阳性数的44．4％）。结果发现29例异常核型，其中21-三体14例，18-三体5例，性染色体异常3例，其他异常核型7例，异常发生率2．49％。结论母血清产前筛查结合羊水诊断能够有效的避免胎儿染色体异常的发生。     

Morphological classification of nuchal skin in human fetuses with trisomy 21, 18, and 13 at 12—18 weeks and in a trisomy 16 mouse

An increase in the nuchal translucency that can be detected at 10–14 weeks of gestation by ultrasound forms the basis for a screening test for chromosomal abnormality. Several mechanisms leading to this increase in skin thickness have been proposed, including changes of the extracellular matrix, cardiac defects and abnormalities of the large vessels. This study examines the composition of the extracellular matrix of the skin in gestational age-matched fetuses with trisomy 21, 18 and 13 from 12–18 weeks. Immunohistochemistry was applied with monoclonal and polyclonal antibodies against collagen type I, III, IV, V and VI and against laminin and fibronectin. Collagen type VI gene expression was further studied by in situ hybridization to detect differences in expression patterns of COL6A1, COL6A3 and COL1A1 between normal fetuses and those with trisomy 21. The ultrastructure of tissue samples was studied by transmission electron microscopy (TEM) and additionally by immunogold TEM. Further, we examined the morphology of the skin in an animal model for Down’s syndrome, the murine trisomy 16, by light and TEM. The dermis of trisomy 21 fetuses was richer in collagen type VI than that of normal fetuses and other trisomies, and COL6A1, located on chromosome 21, was expressed in a wider area than COL6A3, which is located on chromosome 2. Collagen type I was less abundant in the skin of trisomy 18 fetuses, while the skin of all three trisomies contained a dense network of collagen type III and V in comparison with normal fetuses. Collagen type IV, of which two genes are located on chromosome 13, was expressed in the basement membranes of the skin in all fetuses and additionally in the dermal fibroblasts only of trisomy 13 fetuses. Likewise, laminin was present in all basement membranes of normal and trisomic fetuses as well as in dermal fibroblasts of fetuses with trisomy 18. LAMA1 and LAMA3 genes are located on chromosome 18. Dermal cysts were found in the skin of trisomy 18 and 13, but not in trisomy 21 and normal fetuses. Ultrastructural findings showed that an extracellular precipitate containing glycosaminoglycans was regularly present in the skin of trisomy 21 fetuses and murine trisomy 16 embryos. In conclusion, this study suggests that the skin edema in fetal trisomies is characterized by specific alterations of the extracellular matrix that may be attributed to gene dosage effects as a result of a genetic imbalance due to the condition of fetal trisomy.     

孕中晚期21三体产前诊断的结果分析

目的通过孕中晚期21三体、18三体产前诊断的结果分析,评价孕中晚期产前诊断的价值。方法对怀孕16～29周符合产前诊断条件的孕妇经知情同意后,在B超介导下对孕16-24周孕妇行羊膜腔穿刺,抽取羊水;孕25-29周孕妇行胎儿脐静脉穿刺,抽取脐带血,进行细胞培养,染色体核型分析。结果在2689例产前诊断病例中发现异常核型149例,异常率为5.54%。常染色体结构异常-倒位核型43例、平衡易位18例、罗氏易位8例,常染色体非整倍体数量异常（21三体、18三体、13三体）48例,性染色体数量异常15例,性染色体结构异常12例,其它核型异常5例。常染色体非整倍体数量异常（21三体、18三体、13三体）占发现异常核型的32.2%（48/149）,为主要异常核型。结论羊水细胞、脐带血染色体核型分析是目前产前诊断21三体、18三体、13三体染色体异常胎儿必不可少的检查方法,对于预防缺陷儿出生,提高人口素质,优生优育具有十分重要的意义。     

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。