细菌人工染色体标记——微球鉴别技术在染色体异常产前诊断中的价值及适用人群

目的探讨细菌人工染色体标记—微球鉴别(Bo Bs)技术在染色体异常产前诊断中的价值及适用人群,为临床诊断提供参考依据。方法对122例因无创产前筛查(NIPT)高风险、产前血清学筛查高风险或35岁以上高龄就诊的单胎孕妇取绒毛或羊水,同时进行Bo Bs检测和染色体核型分析。结果除去1例羊水标本培养失败未进行核型分析,其余标本Bo Bs结果均与核型分析结果一致。在43例NIPT筛查高风险、47例血清学筛查高风险及32例高龄妊娠孕妇标本中确诊例数依次为27例、1例和0例;此28例染色体异常标本包括21-三体18例、18-三体6例和XXY 4例;其中1例21-三体为嵌合型,核型分析结果为47,XN,+21,der (21; 21)(q10; q10)[13]/46,XN [25]。此外,Bo Bs技术还能检测9种常见微缺失综合征,但在本次检测未遇到阳性样本。结论 Bo Bs技术可为染色体分析提供快速、准确、高通量的产前诊断,还可作为传统核型分析细胞培养失败等特殊情况的补救措施,尤其适用于NIPT筛查高风险需进一步快速确诊的孕妇以及有微缺失综合征高危表征的孕妇;而血清学筛查高风险及高龄妊娠孕妇,从技术应用的阳性检出率和成本考虑,则不建议作为首选群体。     

Rapid diagnosis of fetal chromosomal abnormalities by fluorescence in situ hybridization

INTRODUCTION: In the course of the Down-screening protocol there are possibilities today for rapid diagnosis of aneuploidies among high-risk pregnancies identified by non-invasive screening tests, however, the diagnostic value of these molecular genetic tests are debated. AIM OF THE STUDY: In this prospective study, data about the reliability of one of the rapid tests, namely; interphase fluorescence in situ hybridization (int-FISH) was to be gathered by the authors. METHODS: For the period between May 2002 and September 2006 all of the 1279 fetal sample were examined both with int-FISH and full karyotyping. RESULTS: Extra or absent signal was detected in 47 cases (3.7%) (trisomy 21 in 32, various other numerical abnormalities in 15 cases). All of these numerical aberrations were confirmed by metaphase analysis without false positivity or negativity. In 19 cases the finding of int-FISH was negative, however, full karyotyping disclosed abnormalities (in 12 of these 19 cases, the abnormality was balanced). Only 4 of the 1279 fetuses (0.3%) (3 small extra marker chromosomes, 1 de novo unbalanced translocation) were to be found, who would have been born with phenotypical abnormalities without metaphase analysis (2 of them had suspect ultrasound signs). CONCLUSION: Although more analysis are needed, based on the results of this study it is to be concluded that rapid molecular genetic methods like int-FISH might be accepted as a diagnostic tests of fetal aneuploidy, if its use were restricted to high risk pregnancies identified by advanced maternal age and non-invasive maternal screening only. However, full karyotyping is needed in cases with familial translocation and abnormal 2nd trimester ultrasound signs.     

产前诊断中胎儿新发生染色体异常的临床结局分析

目的分析产前诊断中胎儿新发生染色体异常的临床结局。方法对某院1997年1月～2009年12月1346例产前诊断细胞染色体核型分析发现的6例新发生的胎儿染色体异常病例进行分析,观察6例新发生的胎儿染色体异常病例的细胞遗传学检测结果、产前超声检查结果及妊娠结局。结果 6例新发生染色体异常的胎儿中,非平衡性染色体异常4例,占66.7%;2例平衡性染色体异常,占33.3%;4例非平衡染色体异常的胎儿中有2例选择引产终止妊娠,有1例足月分娩,1例出生后失访。足月分娩者随访至2周岁发现语言功能发育迟缓。2例平衡性染色体异常的胎儿均足月分娩,出生后随访未发现异常。结论新发生染色体异常的胎儿表型可通过详细的染色体核型分析以及进一步的分子细胞遗传学检测所提供的染色体成分进行预测,产前超声结构畸形检查可为妊娠结局的评估提供有力的参考依据。     

染色体微阵列芯片分析技术在产前诊断中的应用

目的探讨染色体微阵列芯片分析(CMA)技术在产前诊断中的应用价值。方法选择2015年1月-2016年8月在南方医科大学附属佛山市妇幼保健院产前诊断中心就诊的经超声检测为胎儿畸形的孕妇为研究对象,对其中100例自愿进行产前诊断的孕妇进行常规染色体核型分析及CMA检测结果 100例结构异常的胎儿中,染色体拷贝数异常13例(13.0%),其中9例CMA及染色体核型分析均检测出异常;染色体核型分析正常的90例病例中,有4例CMA检测出致病基因(4.4%);CMA检测为良性染色体拷贝数变异(CNV)的84例病例中,有1例染色体核型分析为平衡易位。结论 CMA检测在超声结构异常的胎儿的遗传学分析中具有重要的应用价值。但CMA分析技术本身有局限性如不能检测平衡易位,目前尚不能完全替代染色体核型分析。     

Cost-benefit analysis of amniocentesis in the prenatal diagnosis of chromosome abnormalities

The article presents a cost-benefit analysis of amniocentesis for detection of chromosomal anomalies based on data (1985/87) collected in the Marseille area. In this geographic area, it is possible to confront, in an exhaustive manner, pregnant women's access to amniocentesis and incidence of fetal anomalies due to chromosomal aberrations. Results show that prenatal diagnosis is highly cost-beneficial, the average cost of one "avoided" case of Down's syndrome being lower than the lifelong costs of care for such a child. However, the study emphasizes that the cost-benefit ratio is highly sensitive to the implicit value society affects to the loss of "normal" fetuses through spontaneous abortions provoked by amniocentesis and because of terminations of pregnancy following diagnosis of minor fetal anomalies. The study also shows that lowering maternal age limit for access to free-of-charge amniocentesis from the current 38 years of age to 35 would have been cost-beneficial. Such lowering of the maternal age limit is discussed and compared with other indications which might be used for systematic access to amniocentesis.     

城市孕妇对无创产前基因检测胎儿染色体异常的认知水平及接受程度调查

目的 了解城市孕妇对无创产前基因检测（NIPT）胎儿染色体异常的认知水平及接受程度。方法 采用简单随机抽样方法对四川省攀枝花市某医院产科门诊的孕妇作为调查对象进行问卷调查,内容包括调查对象基本情况、NIPT技术相关知识及接受程度,对NIPT相关知识认知情况及接受情况的相关因素进行分析。结果 本研究共对1 156名孕妇进行调查,调查对象年龄最小20岁,最大45岁,以汉族为主,占78.98%,文化程度以高中/中专为主,占52.51%。孕周以12~27周为主,占51.04%。孕次1次占39.01%,2~5次占39.97%。产次0次者占51.04%,1次者占30.36%。调查对象中NIPT高认知水平者有486人,占42.04%,愿意及已选择NIPT筛查者占48.01%。在NIPT相关知识中,NIPT、NIPT检测方法、NIPT与有创诊断区别知晓率相对较高,分别为60.73%、60.03%和58.04%,孕12周开始即可进行筛查、NIPT检测结果影响因素的知晓率相对较低,分别为30.02%和19.98%。多因素分析显示年龄越大（OR=1.303）、文化程度越高（OR=1.191）、有不良孕产史（OR=1.171）、家庭月均收入越高（OR=1.394）和NIPT认知水平高（OR=1.164）的孕妇愿意或已选择NIPT的可能性越大。结论 攀枝花市孕妇对NIPT技术的认知水平并不理想,对无创产前基因检测技术的接受度不高,年龄、不良孕产史、认知水平、文化程度和家庭经济收入水平是影响该城市孕妇是否选择该技术的主要因素。     

产前超声诊断胎儿神经系统畸形的临床价值

目的 探讨产前常规超声检查在胎儿神经系统畸形筛查方面的临床应用价值.方法 对27例经随访及引产证实的中枢神经系统畸形胎儿进行回顾性分析.结果 27例畸形儿中,其中脊柱裂和脊髓脊膜膨出11例,Dandy-Walker畸形3例,脑脊膜膨出3例,脑积水3例,无脑儿1例,全前脑2例,胼胝体发育不全2例,脉络丛囊肿1例,蛛网膜囊肿1例,产前超声诊断准确率为88.90%,误诊率7.40%,漏诊率7.40%.结论 产前超声检查对胎儿中枢神经系统畸形诊断准确率高,具有十分重要的临床应用价值.     

Results of prenatal echographic studies in the diagnosis of pediatric surgical abnormalities

In 180 newborns with congenital anatomical anomalies, admitted to the Department of Paediatric Surgery, Sophia Children's Hospital, Rotterdam, we retrospectively determined whether ultrasound studies had been performed during the second and third trimesters of pregnancy. The correlation between prenatal and postnatal diagnoses was investigated as well. Ultrasound study had been performed in 86 if the 180 pregnant mothers (48%). In 41 cases the anomaly of the newborn had not been diagnosed prenatally. In 45 cases anomaly had been diagnosed prenatally. The ultimate diagnosis was the same as the prenatal diagnosis in 35 patients and was different in 10. We conclude that routine prenatal ultrasound study in the second or third trimester of pregnancy, aimed at detecting congenital anatomical anomalies to be treated by the (general) paediatric surgeon, provided little certainty about the health of the baby. Permanent education of obstetricians, and at the slightest doubt referral to one of the University Hospital Centres for specific ultrasound study, are mandatory in order to be able to correctly inform an increasing number of parents about the prospects of their unborn child.     

我国生育政策演进与人口均衡发展 —— 从独生子女政策到全面二孩政策的思考

  目的  了解生育政策改变对甘肃省兰州市出生缺陷监测结果的影响效应。  方法  收集2010 — 2019年兰州市出生缺陷监测资料,按甘肃省生育政策实施时间,分为独生子女（2010年1月 — 2014年3月）、单独二胎（2014年4月 — 2015年12月）、全面二胎（2016年1月 — 2019年12月）3个时期,共计6 826例产妇 – 出生缺陷儿对子,比较不同生育政策时期的产妇特征、患儿特征以及主要出生缺陷情况。  结果  对出生缺陷监测人群分析显示,独生子女时期、单独二胎时期和全面二胎时期的对子数分别是1 511、1 174和4 141例。在全面二胎时期,产妇文化程度和收入增高,高龄产妇、经产妇占比增加,妊娠周数 < 28周者增多,患儿胎龄和胎重显著降低,且均存在统计学差异（均P < 0.05）。控制混杂因素后,多因素logistic回归分析显示,相对于独生子女时期,在全面二胎时期先天性心脏病（OR = 4.228）、总唇裂（OR = 1.207）、多指趾（OR = 2.252）、并指趾（OR = 1.788）、马蹄内翻足（OR = 1.602）和唐氏综合征（OR = 3.065）的风险上升,多发缺陷（OR = 0.147）风险下降。  结论  全面二胎时期,兰州市出生缺陷监测地区高龄、经产妇占比增加,出生缺陷发生风险较高。     

Domestic violence: possibilities and limitations in coping

This qualitative study assesses how women, in situations of domestic violence and examined at the Institute of Forensic Medicine, deal with this adversity and identifies protection strategies to cope with it, considering the support required and obtained from their relational and institutional environments. Ten women were interviewed and the data were analyzed using thematic content analysis. Search for help primarily occurs in the women's social milieu, with family and friends and health and legal services being sought. In such a quest, established bonds may either become an obstacle to coping and make these women vulnerable to violence or protect and strengthen them during coping. In the identification of these women's social and health needs, the aggravating circumstances of violence are only superficially addressed by professionals. New strategies to implement professional actions should be devised in order to provide integral and humanized care.     

Examples of preimplantation genetic diagnosis versus prenatal diagnosis in carriers of genetic abnormalities: advantages and disadvantages

Preimplantation genetic diagnosis (PGD) is a method for identifying genetic abnormalities in embryos obtained via in-vitro fertilisation before their implantation. There are many indications for PGD, which offers an alternative to prenatal diagnosis, although each modality has its advantages and drawbacks. In three female patients there were clear indications for PGD: carriage of the gene for myotubular myopathy, a balanced complex chromosomal translocation, and a Robertsonian translocation in the male partner, respectively. The first patient eventually abandoned PGD and chose prenatal diagnosis. She had a total of three abortions. A twin pregnancy with a so-called foetal reduction resulted in the birth of a genetically normal child. The second patient had one spontaneous abortion and subsequently underwent two PGD cycles, resulting in an uncomplicated pregnancy and the delivery of a genetically normal child. The third patient had one genetically normal child and six spontaneous abortions. She then underwent the PGD procedure successfully and is expecting twins; the pregnancy has been uncomplicated. During preconception counselling of couples at high genetic risk, physicians should be aware of PGD as an alternative to prenatal diagnosis.     

探讨无创产前基因检测胎儿染色体非整倍体技术的应用

我国为出生缺陷的高发国家,降低出生缺陷,以预防为主.目前我国以产前血清学筛查、超声检测和产前诊断技术为主要预防手段,随着母体外周血中游离DNA的发现和基因测序技术的发展,无创胎儿染色体非整倍体检测技术集合了多项优势,为临床提供新的技术支持.本研究对近年来无创产前诊断国内外发展状况进行综述,为进一步临床研究与应用提供参考.     

应用QF-PCR技术对胎儿常见非整倍染色体的快速诊断

目的探讨多重荧光定量PCR(QF-PCR)技术在快速产前诊断常见非整倍染色体中的临床应用价值。方法应用QF-PCR技术快速诊断205例产前羊水标本中的13、18、21、X、Y染色体,并与常规核型分析结果对比。结果 205例产前诊断标本QF-PCR法共检出17例非整倍染色体,其中10例21三体、3例18三体、1例13三体和3例性染色体异常,与染色体核型分析结果一致;另有1例平衡易位、1例嵌合体及3例倒位核型无法通过QFPCR检测出,两种方法一致性97.6%。结论QF-PCR作为一种快速诊断常见非整倍染色体技术,结果准确可靠,可在产前诊断应用中发挥重要作用。     

细菌人工染色体微珠技术标记在胎儿染色体疾病诊断中的应用价值研究

目的探讨细菌人工染色体微珠标记技术(Bobs)在胎儿染色体疾病诊断中的应用价值。方法对1 056例行羊膜腔穿刺术的胎儿羊水细胞行染色体核型分析及Bobs检测,对部分Bobs检测阳性样本行染色体微阵列、荧光原位杂交方法验证。结果 Bobs准确验证了核型分析发现的所有16例染色体非整倍体异常、1例Wolf-Hirschhorn综合征以及3例性染色体异常嵌合体,此外在核型正常样本中检出2例22q11微重复以及1例母体细胞污染病例。结论相较于染色体核型分析,Bobs具有通量高、检验快速及分析简便的优势,适宜作为介入性产前诊断的常规补充项目。