Prenatal cytogenetic diagnosis--a current audit. A review of 2000 cases of prenatal cytogenetic diagnoses after amniocentesis, and comparisons with early experience

An audit of 2000 cases of prenatal cytogenetic diagnoses is presented. This comprises two consecutive series of 1000 cases (1974-1980 and 1980-1983). Chromosomal studies were performed after mid-trimester amniocentesis. For both series detailed results of the reasons for referral and the outcome of laboratory studies and pregnancy follow-up (in 95% of cases) are presented. In current practice 75% of prenatal cytogenetic diagnoses were for advanced maternal age. Ten per cent of tests were undertaken because of a family history of Down's syndrome. The detection rate of chromosomal abnormality in prenatal cytogenetic diagnoses was 2.06%. Two per cent of amniotic cell cultures failed to grow, necessitating a repeat amniocentesis. The rate of culture failure due to undefinable causes was 0.55%. Fetal loss after amniocentesis for prenatal cytogenetic diagnosis at 16 weeks' gestation has halved since 1980, with a current miscarriage rate of 0.6% within four weeks of the procedure. One maternal death (as a result of amniotic fluid embolism) and one case of amnionitis occurred in the first series of 1000 consecutive cases (up to 1980), but no such complication has occurred since. Secular trends in the indications for referral, laboratory complications, clinical outcome and diagnostic patterns are presented.     

基于微阵列芯片的比较基因组杂交技术在临床实验室产前诊断中的应用

Array-based comparative genomic hybridization (array CGH), a method used to detect gains or losses of genetic material, has recently been applied to prenatal diagnosis of genomic imbalance in the clinical laboratory setting. This new and exciting diagnostic tool represents a major technological step forward in cytogenetic testing and addresses many of the limitations of current cytogenetic methods.Conventional chromosome analysis, the current gold standard in prenatal diagnosis, focuses primarily on the detection of common aneuploidies and is limited by its capacity to detect only those copy number changes that are large enough to be microscopically visible (typically 5-6 Mb in size at the 500 band level). In contrast, array CGH analysis simultaneously evaluates regions across the entire genome and al-lows for detection of unbalanced structural and numerical chromosome abnormalities of less than one hun-dred kb. Array CGH analysis also overcomes some of the limitations of chromosome analysis, such as the requirement for cell culture and longer reporting time, by using direct uncultured fetal specimens. With many diagnostic laboratories now embracing this technology, the past year has seen tremendous growth in the use of array CGH analysis for prenatal diagnosis. This review aims to summarize array CGH methodology and its current applications in prenatal diagnosis.     

深圳龙岗区孕前夫妇地中海贫血筛查及干预状况分析

目的 了解近年来深圳市龙岗区已婚孕前夫妇地中海贫血基因型分布情况,分析已婚孕前夫妇地中海贫血筛查干预状况。方法 对本辖区3 399对已婚孕前育龄夫妇地中海贫血知识干预前后问卷;用血常规方法进行初筛,以单或双方MCV和（或）MCH异常定为初筛阳性夫妇,再行血红蛋白电泳,结合HbA₂结果定为筛查阳性夫妇,最后做α、β-地中海贫血基因诊断确诊;对高危夫妇给予遗传咨询和追踪随访指导怀孕后接受产前诊断。结果 干预后已婚孕前育龄夫妇地中海贫血知识答对率比干预前显著提高(P<0.01);经血常规初筛确定815对为初筛阳性夫妇（24.0%）;后经血红蛋白电泳确定303对为筛查阳性夫妇（8.9%）;再经地中海贫血基因诊断确诊136对为地中海贫血夫妇（4.0%）,其中α、β和αβ复合型地中海贫血分别为181、83和8例。检出常见α-地贫基因型频率依次为--SEA/αα（59.7%）、-α3.7/αα(23.8%)等;检出常见β-地贫基因型频率分别为CD41-42(34.9%)、IVS-Ⅱ-654(28.9%)等;检出高风险家庭17个,夫妇双方均为--SEA/αα。结论 龙岗区是地中海贫血高发区,高风险家庭也较多,因此实施孕前人群地中海贫血筛查干预,可有效降低中间型地贫,避免重型地中海贫血患儿的出生,提高辖区出生人口素质。     

社区孕前保健网底建设探索研究

背景　我国是出生缺陷高发国家，出生缺陷日益成为突出的公共卫生和社会问题。为降低出生缺陷，相关权威部门颁布并更新了《孕前与孕期保健指南》，国家实行免费孕前优生健康检查。由于宣传力度不够等原因，国家免费政策遇冷。目前社区缺少孕前健康教育专业人员。目的　总结上海市宝山区淞南镇社区卫生服务中心（简称中心）在孕前保健网底建设探索中取得的经验。方法　2018年3-12月，中心利用卫生计生系统合二为一、统一管理的有效模式，将卫生服务、计生指导与管理整合后的社区孕产期保健管理网络为基础，创建社区孕前保健管理网络，培养社区孕前保健管理队伍，广泛宣传孕前优生知识和国家免费孕前优生健康检查政策，将分级诊疗、上下联动的医疗模式运用于孕前保健。于宣传前后，对社区孕前保健管理队伍成员开展孕前优生知识知晓情况的调查；对服务对象开展不良孕产史、国家免费政策知晓情况、孕前优生知识知晓情况、孕前保健知识需求情况、孕前优生健康检查情况的调查。结果　淞南镇共240对夫妇438例接受了孕前保健健康教育服务。宣教后，孕前保健管理队伍成员免费孕前检查服务内容、服用叶酸时间、服用叶酸原因、人工流产后适宜受孕时间知晓率均高于宣教前（P<0.05）。宣教后，438例（100.0%）服务对象均知晓国家免费政策，高于宣教前的359例（82.0%）（P<0.05）。宣教后，服务对象孕前健康准备时间、孕前不宜接触的毒害物、孕前健康准备内容、开始服用叶酸时间知晓情况均高于宣教前（P<0.05）。宣教后，96对（40.0%）夫妇已作或已预约孕前优生健康检查。2017年按照原来的工作模式，免费孕前优生健康检查数未完成目标任务，目标任务83对，实际完成76对；2018年按照新的孕前保健工作模式，免费孕前优生健康检查数超额完成目标任务，目标任务75对，实际完成95对。结论　新创建的社区孕前保健管理网络具有较强的管理能力和专业优势，又具有成熟的社会宣传和政策执行能力，通过分级诊疗、上下联动的医疗模式拓展了社区孕前保健服务内涵，此模式运用前景广阔；对育龄夫妇进行一级干预，符合我国当下的形势需求，其简单易行、操作性较强、经济成本低、作用范围广，值得推广。     

21-三体患儿的年轻双亲染色体随体联合率的研究

观察了10对21—三体患儿的23～34岁父母的外周血淋巴细胞G显带染色体随体(S)联合率,另对相应年龄内的正常夫妇和曾流产3次及有流产、死胎史以及生产过其他类型畸胎者夫妇各10对作了观察比较。结果:21—三体患儿双亲组的染色体21-D及21-G的S联合率明显高于其他4组(P<0.01)。初步认为:年轻夫妇的21-D及21-G S联合率增高者,生育21—三体患儿的可能较大,应仔细作产前诊断,防止21—三体患儿诞生。     

49例同型地中海贫血携带者产前基因诊断分析

目的 探讨防止严重类型地中海贫血(简称地贫)患儿出生的有效手段和重要意义.方法 2013年1月至2015年12月于该院产前检查的孕妇及配偶通过地贫筛查和基因诊断,对确诊的49例同型地贫携带者夫妇进行羊水地贫产前基因诊断,并在产前诊断后进行髓访.结果 在49例同型地贫携带者夫妇中,基因诊断检测出α-地贫主要突变类型为--SEA/αα (50.0％)、-α3.7/αα (36.5％)、-α4.2/aa(11.5％),p地贫主要突变类型为CD17/N(42.0％)、CD41-42/N (26:0％)、IVS-Ⅱ-654/N(22.0％).产前诊断检测出HbH病4例,Bart's水肿胎儿2例,重型β-地贫10例,α-地贫携带者19例,β-地贫携带者10例,α-地贫合并β-地贫1例,健康胎儿3例.随访结果与产前诊断结果相符.结论 通过开展地贫产前筛查和产前诊断能有效地防止重症地贫患儿出生.     

中山市小榄地区β－地中海贫血产前筛查和产前诊断状况

目的：调查中山市小榄地区地中海贫血产前筛查中夫妻双方β－地中海贫血（简称β－地贫）的基因突变类型、分布特征及产前诊断情况。方法采用血常规结合血红蛋白电泳法对孕妇血样进行地中海贫血产前筛查,对筛查阳性的疑似地贫携带者,采用单管多重跨越断裂点PCR技术和PCR－寡核苷酸探针反向斑点杂交法（ PCR－RDB）进行地贫基因检测,地贫基因检测阳性者,则要求召回配偶。如果夫妻双方同时携带β－地贫基因,则建议其做产前诊断。结果产前地中海贫血筛查孕妇22220名,5560例地贫血液学表型筛查为阳性,进行地贫基因检测后发现2621例诊断阳性,其中携带β－地贫基因突变的1065例,含β复合α地贫突变的138例。有1164名配偶接受召回进行地贫基因诊断,204例诊断阳性,其中携带β－地贫基因的80例,含β复合α地贫突变的11例。所有个体共检出12种β－地贫基因突变类型,构成比靠前的为CD41－42（－TCTT）突变,分别占48.75％（39／80,男方）和44.41％（473／1065,女方）;其次为CD17（A→T）突变,分别占15.00％（12／80,男方）和19.72％（210／1065,女方）。夫妻双方为β地贫基因携带者的22对,20对进行产前诊断,9对夫妻的胎儿诊断为重型β地贫;另有2对拒绝产前诊断,随访发现其中1对夫妻生出重型β地贫患儿。结论小榄地区常居人群β－地贫基因携带率较高,地贫产前筛查及产前诊断依从性较差,应加强婚育人群地贫防控相关知识教育,确保所有婚育人群了解重型地贫的危害性及严重性,对开展地贫群体干预和促进优生优育具有重要意义。     

First trimester prenatal diagnosis: earlier is not necessarily better.

In the past few years considerable attention has been given to a relatively new method of prenatal diagnosis known as chorionic villus sampling (CVS). Because CVS can be performed in the first trimester it is hailed by many as a significant advance over amniocentesis. What has not been as publicized, however, are the disadvantages of CVS and earlier prenatal diagnosis. The emotional costs of CVS in terms of the greater number of both spontaneous and selective abortions following CVS, the use of CVS for sex selection and, because of the greater social acceptability of first trimester abortion, the possibility of increased pressure on women to undergo prenatal diagnosis by health insurance companies, medical professionals and government agencies, all need to be weighed against the advantages of early prenatal diagnosis.     

Non-invasive Prenatal Gene Diagnosis: Progress through Cell-free Fetal DNA and RNA in Maternal Plasma and Urine

Non-invasive prenatal gene diagnosis has been developed rapidly in the recent years, and numerous medical researchers are focusing on it. Such techniques could not only achieve prenatal diagnosis accurately, but also prevent tangential illness in fetuses and thus, reduce the incidence of diseases. Moreover, it is non-invasive prenatal gene diagnosis that prevents potential threaten and danger to both mothers and fetuses. Therefore, it is welcomed by clinical gynecologist and obstetrian, researchers of medic...     

Changes in maternal age distribution and their possible impact on demand for prenatal diagnostic services

Between 1977 and 1985 there was a 65% increase in births to women aged 35 or more in England and Wales, but only a 15% increase in all births. Two factors of roughly equal importance were responsible for this differential increase. Firstly, the proportion of older women (35-44) among all women of reproductive age (15-44) increased from 28% in 1977 to 31% in 1985; and, secondly, in the same period the fertility rate for women aged 35-39 increased from 18.2 to 24.1 per 1000 and for women aged 40-44 from 4.1 to 4.6 per 1000. The increased fertility rate among older women is not due to an extension of the reproductive period but to a delay in childbearing. This delay was seen in women married only once and also in those who had remarried. As prenatal diagnosis for the exclusion of chromosome abnormalities is customarily offered to older mothers the increased numbers of women aged 35 or more and their increased fertility rate have important implications for the provision of obstetric and laboratory services. There were 51,859 live births to women aged 35 and over in 1985; the projected figure for 2001 is 85,000. If the use of prenatal diagnosis continues to increase facilities for about 70,000 prenatal cytogenetic analyses will be needed in 2001.     

地中海贫血干预措施预防出生缺陷的效果分析

目的探讨地中海贫血干预措施预防出生缺陷的效果。方法对门诊所有产检孕妇及其丈夫27076例进行地中海贫血相关知识宣教,同时进行地中海贫血筛查,双方筛查阳性的夫妇均进行地中海贫血基因诊断,对高风险的孕妇进行产前诊断,确诊重型地中海贫血胎儿者建议终止妊娠。结果共筛查27076例,其中建卡孕妇筛查14877例,丈夫筛查12199例。地贫筛查双方均阳性的夫妇341对,其中高风险的孕妇148例进行产前诊断,确诊重型地中海贫血胎儿28例,均引产。结论孕期地中海贫血干预可以避免重度地中海贫血胎儿的出生,从而降低出生缺陷发生率。     

小头畸形产前诊断与管理的研究进展

 小头畸形是指胎儿头围明显小于同孕龄胎儿正常头围,可能是一种正常变异,也可能是神经系统畸形的标志。目前临床缺乏统一的诊断标准,不同原因以及不同程度的小头畸形预后差别很大,其中环境暴露和遗传因素是小头畸形最常见的原因。近年来,随着影像学及二代测序技术的快速发展,小头畸形的产前诊断水平相应提高。本综述比较了小头畸形不同诊断标准的差异,分析小头畸形的病因,包括感染的流行病学、传播及临床特征,并重点对小头畸形的产前诊断及孕期管理的相关研究进展进行了综述。     

用等位基因特异性PCR进行β-地中海贫血产前基因诊断

目的:对两对有重型β-地中海贫血患儿家族史的夫妇进行产前基因诊断。方法:应用等位基因特异性聚合酶链反应(PCR)技术检测两对夫妇及其高风险胎儿的5种β-地中海贫血突变类型:CD41-42(-CTTT)缺失突变、IVSII654(C→T)突变、CD17(A→T)无义突变、TATA盒nt-28(A→G)突变和CD71-72(+A)移码突变。结果:家系1的父亲为TATA盒nt-28(A→G)/N杂合子,母亲为CD41-42(-CTTT)/N杂合子,胎儿正常;家系2的父亲为CD41-42(-CTTT)/N杂合子,母亲为CD71-72(+A)/N杂合子,胎儿为CD41-42(-CTTT)/CD71-72(+A)双重杂合子;上述2例胎儿出生及引产后的基因分析验证结果与产前基因诊断完全一致。结论:等位基因特异性PCR能准确地对β-地中海贫血高风险胎儿进行产前基因诊断,对预防重型β-地中海贫血患儿的出生具有重要意义。     

SRY基因在遗传性疾病产前性别鉴定中的诊断价值

目的:探讨SRY基因在妊娠早期基因诊断中的价值.方法:经阴道获取胎儿细胞,应用PCR方法扩增SRY和DYZ1基因片段,以染色体核型分析作为金标准,比较它们的敏感度、特异度和一致性.结果:SRY-PCR的敏感度、特异度和一致性均高于DYZ1-PCR.结论:在用于性连锁遗传性疾病的产前性别诊断中,SRY基因具有明显优势,值得推广.     

Control and prevention of the genetic load of haemoglobinopathies in India

Haemoglobinopathies and thalassaemia are inherited disorders which affect a large number of individuals in India. With a population of 950 million and a birth rate of 28 per thousand, it has been estimated that there would be about 42 million carriers and about 12,000 infants born each year will be inheriting a major haemoglobin disorder in India. In view of this heavy genetic load, frequent blood transfusions, high cost of treatment and management, physical trauma, and psychological and mental harassment to the patients and their families, it has been realized that the preventive genetic approach is the most suitable for the Indian setting. After carrier detection, prenatal diagnosis and genetic counselling are important options for couples at high risk for haemoglobinopathies. A prerequisite for a successful prevention and control programme is health education, public awareness and sensitization, and screening of the population for identification of heterozygotes or carriers in the community.     

928例孕中期羊水细胞染色体核型分析

目的评价产前诊断指征在胎儿染色体病诊断中的意义。方法对940例妊娠中期孕妇行羊膜腔穿刺术抽羊水进行羊水细胞染色体核型分析。结果940例孕妇羊水培养成功928例,成功率98.72%。发现异常核型26例,占2.80%。其中,各类三体11例占42.31%,为最主要的异常核型。高龄(≥35岁)孕妇胎儿染色体数目异常的检出率为1.94%(6/310),明显高于非高龄孕妇胎儿0.65%(4/618)的检出率(P=0.037)。另外,35岁以下唐氏筛查高风险者胎儿确诊阳性率为0.69%(3/432),远远高于普通人群水平。结论合理应用产前诊断指征可以明显提高染色体病的产前诊断效力。     

实时PCR和cycling probe技术检测母血浆游离胎儿DNA筛选重型β地中海贫血胎儿

OBJECTIVE: To analyze cell-free fetal DNA in maternal plasma for prenatal screening of beta-thalassaemia major. METHODS: Six couples undergoing prenatal diagnosis of beta-thalassaemia (gestational age range 23-26 weeks) were enrolled in this study. The husbands were all carriers of the CD17(A-->T) mutation, and the wives carreid another beta-thalassaemia mutation. The allele-specific primers and two fluorescent cycling probes were synthesized for the detection of the CD17(A-->T) mutation, using FAM and HEX fluorescence labeling, respectively. The cell-free fetal DNA in the maternal plasma was detected using real-time PCR, and the fetal genotype was confirmed by cord blood conventional prenatal diagnosis. RESULTS: In the 6 pregnancies, FAM and HEX fluorescent signals were detected in 3 maternal plasma samples; in the other 3 samples, only FAM fluorescent signals were detected, suggesting the absence of paternally derived CD17(A-->T) mutation. CONCLUSION: Examination of cell-free fetal DNA in maternal plasma using real-time PCR and cycling probe technology can be effective means for prenatal screening of beta-thalassaemia major.     

Pregnant women with fetal abnormalities: the forgotten people in the abortion debate

Abortion law reform focuses on early abortion. Women wanting to have a family who have a fetal abnormality detected later in pregnancy are neglected in the debate and harmed by the consequences of current legal uncertainty. Unclear abortion laws compromise: the quality of prenatal testing; management when an abnormality is found; and patient care, through obstetricians' fears of legal repercussions. Women carrying a fetus with an abnormality are being denied abortion, even when the abnormality is so severe that non-treatment would be an option if the baby were born. Many women are likely to refuse to consider motherhood if they are denied appropriate prenatal testing and access to abortion if serious abnormalities are detected. Current abortion laws result in discriminatory and inconsistent practices, where access to prenatal testing and termination of pregnancy depends on location, the values of the treating doctor or hospital ethics committee, and a woman's personal resources. Legal certainty is needed to reduce the suffering of couples wanting to have a family.     

泰国缺失型α-地中海贫血1导致血红蛋白H病的产前诊断

目的探讨泰国缺失型α-地中海贫血1（泰国缺失型）导致的血红蛋白H病（Hb H病）产前诊断方法。方法收集2010年6月～2011年12月间在广西妇幼保健院优生遗传门诊就诊的3对可能生育泰国缺失型Hb H病胎儿夫妇,采用先后检测常规6种常见α-地中海贫血（α-地贫）基因型和检测泰国缺失型的方法,对这3对高风险夫妇进行产前诊断。结果 3对夫妇产前诊断胎儿均为Hb H病,1例是泰国缺失型复合右侧缺失型双重杂合子,基因型是（--THAI/-α3.7）;1例是泰国缺失型复合左侧缺失型双重杂合子,基因型是（--THAI/-α4.2）;1例是泰国缺失型复合HbWestmead双重杂合子,基因型是（--THAI/αWSα）。结论综合分析常规检测和泰国缺失型检测结果 ,能有效的产前诊断泰国缺失型导致的Hb H病。     

性染色体异常胎儿畸形形态学特征与临床分析

目的探讨性染色体异常合并先天性畸形的类型及其病理特征,并结合临床资料及产前超声筛查结果进行分析,为孕妇提供选择妊娠结局的科学依据。方法对我院2007年4月至2009年8月2 338例有产前诊断指征的孕妇行羊膜腔或脐静脉穿刺术后进行胎儿染色体核型分析,对终止妊娠后娩出胎儿进行病理解剖,并结合临床资料及超声结果进行对比分析。结果 108例畸形胎儿中共检出18例性染色体异常,其中8例有颈部水囊瘤、生殖器发育异常,其与性染色体异常关系密切,尤其是与Turner综合征(Turner syndrome,TS)。冠状幼稚子宫、心脏畸形、唇腭裂也是常见的畸形。结论性染色体异常也是导致胎儿多发性畸形和性腺发育不全的重要原因,因此应在染色体核型结合超声诊断下慎重选择是否终止妊娠。