双胎妊娠产前筛查和产前诊断

双胎妊娠的产前筛查和产前诊断与单胎比较其准确性差,咨询难度大。双胎妊娠的绒毛膜性诊断是双胎妊娠产前筛查的关键基础,目前不推荐对于双胎妊娠进行唐氏综合征的血清学筛查,而需要重视双胎妊娠早孕期的超声软指标筛查以及其他的结构筛查。无创产前筛查的方法对双胎妊娠有一定的筛查意义。高危孕妇采取介入性诊断技术进行染色体异常的检查时,对于单卵双胎妊娠建议进行1个胎儿的采样,而双卵双胎则需要分别采样,如为胎儿结构异常则无论其绒毛膜性均需要进行分别采样。双胎妊娠的介入性诊断流产率略高于单胎妊娠,手术前需要对孕妇及家属充分地知情告知。     

妊娠11～13~(+6)周超声结构筛查在胎儿中枢神经系统畸形诊断中的应用

目的:探讨规范化早孕期超声结构筛查在胎儿中枢神经系统畸形诊断中的临床价值。方法:对6902例(8336胎)孕11~13~(+6)周胎儿(单胎妊娠5468例,双胎妊娠1434例)行规范化早孕期超声结构筛查,并追踪妊娠过程和临床结局。结果:6902例(8336胎)11~13~(+6)孕周胎儿中产前超声检出中枢神经系统畸形13例(单胎妊娠10例,双胎妊娠3例),其中露脑畸形5例,无脑儿4例,前脑无裂2例,脑膜膨出1例,开放性脊柱裂1例。合并其他结构异常4例,染色体核型异常3例。13例胎儿随访结果:除3例双胎畸形胎儿经选择性减胎术后正常胎儿继续妊娠,余胎儿引产前超声与引产后尸检结果相符合。结论:规范化早孕期超声结构筛查可及早发现胎儿中枢神经系统畸形,对降低畸形胎儿的出生率及指导产科处理均有重要临床价值。     

双胎妊娠非整倍体异常的产前筛查与产前诊断

双胎妊娠非整倍体产前筛查较单胎复杂。应在早孕期确定孕周、绒毛膜性并测量颈项透明层厚度。早孕期联合筛查优于中孕期血清学筛查,但检出率明显低于单胎妊娠。无创产前检查用于双胎筛查仍需更多研究数据。双胎之一胚胎停育将影响早孕期筛查的准确性。产前诊断时区分标记双胎是需要注意的重要问题。     

双胎妊娠的产前筛查、诊断与干预：转诊是关键

双胎妊娠产前筛查和诊断具有极强的专业性和复杂性,颈项透明层（NT）厚度联合外周血游离DNA［无创产前检测（NIPT）］检测可提高非整倍体筛查的检出率,减少不必要的介入性产前诊断。双胎之一胎儿异常后的宫内干预需建立在精准的产前诊断基础之上。双胎妊娠的特殊并发症的诊治应转至专业的产前诊断中心或区域性的胎儿医学中心进行。     

妊娠中晚期超声软指标与胎儿染色体异常及其围生结局

目的:探讨妊娠中晚期超声软指标与胎儿染色体异常的关系及其对妊娠结局的影响。方法:回顾性分析2012年4月至2015年12月于四川省人民医院就诊的妊娠中晚期(孕18~32周)超声检查发现软指标异常但未合并明确结构异常1141例患者的临床资料,分析其产前诊断、胎儿染色体情况及围生结局。结果:1检测出24例胎儿染色体异常,其中10例为唐氏筛查(唐筛)低风险,5例为临界风险,3例为高风险;9例无创基因检测高风险。18例引产,6例正常分娩,新生儿正常。2单项超声软指标异常者胎儿染色体异常检出率为1.81%(20/1107),两项超声软指标异常及以上者胎儿染色体异常检出率为11.76%(4/34);两组比较差异有统计学意义(P0.05)。3不同部位的超声软指标异常胎儿染色体异常检出率:鼻骨缺失或发育不良为31.58%(6/19),颈后皮肤皱褶(NF)增厚为25.00%(1/4),脉络丛囊肿为5.38%(7/130),侧脑室增宽为4.27%(5/117)。结论:妊娠中晚期超声软指标两项及以上异常和鼻骨缺失、发育不良及NF增厚的异常胎儿有较高的染色体异常检出率,建议可行介入性产前诊断;单项超声软指标及其他部位异常的可结合唐筛和无创基因检测,以获得良好围生儿结局。     

cffDNA浓度低NIPT检测失败样本的相关因素和妊娠结局分析

目的 探讨分析胎儿游离DNA(cffDNA)浓度低无创产前基因检测(NIPT)检测失败样本的相关因素和妊娠结局。方法 回顾性收集在2017年至2022年期间在广东省妇幼保健院接受NIPT检测,经两次采集外周血均因cffDNA浓度低NIPT检测失败的样本信息,包括孕妇的临床资料、产前诊断结果、超声结果以及妊娠结局。评估导致cffDNA浓度低相关因素以及后续残余风险。结果 两次采血因cffDNA浓度低NIPT检测失败标本39例,其中双胎10例(25.64%),双胎之一停育/减胎7例(17.95%)。接受介入性产前诊断13例(33.33%),均未检出胎儿染色体异常。孕期超声发现胎儿发育异常9例(23.08%),胎儿宫内发育迟缓6例(15.38%)。所有孕妇均追踪到妊娠结局,其中早产10例(25.64%),自然流产2例(5.13%)。结论 对于NIPT检测失败的病例,应明确原因,孕期出现并发症和不良妊娠结局风险增加,应建议接受进一步的遗传咨询、产前诊断和定期超声监测胎儿生长发育。     

孕妇血中胎儿游离DNA是双胎妊娠无创DNA筛查的关键

越来越多的数据显示无创DNA筛查技术在双胎中具有良好的应用效果,并且被一些指南和文献推荐为双胎妊娠胎儿染色体非整倍体的一线检测方案。无创DNA筛查的关键是胎儿游离DNA浓度,如果浓度达不到检测阈值,将出现假阴性的结果。双胎妊娠孕妇血中的胎儿游离DNA虽然总体比单胎高,但是每个胎儿的DNA比单胎低,因此双胎妊娠的无创DNA筛查更容易出现检测失败和假阴性的结果。另外,临床上双胎一胎消失的情况又增加了假阳性的结果,这些都导致无创DNA筛查在双胎妊娠的筛查中效果不如单胎。基于SNP的无创DNA筛查技术可以准确评估孕妇和每个胎儿的游离DNA浓度,可以有效地保证无创DNA检测的效果,也可以解决消失胎儿对存活胎儿游离DNA干扰的问题。本文将对双胎妊娠胎儿游离DNA在无创DNA筛查中的关键作用进行阐述,以期为双胎的无创DNA筛查在临床上的应用和遗传咨询提供理论依据。     

双胎妊娠产前筛查新进展

正随着辅助生殖技术(ART)的发展和高龄产妇生育需求的增加,双胎妊娠的发生率大大增加,双胎妊娠较单胎妊娠相比,胎儿出生缺陷的发生率增加,因此对双胎妊娠进行产前筛查和必要时的产前诊断至关重要。双胎妊娠产前筛查较单胎复杂,传统的早中孕期筛查方案是否与单胎妊娠相同?外周血胎儿游     

双胎妊娠产前筛查与诊断技术规范（2021年更新版）

        双胎妊娠流产、死亡、胎儿畸形及胎儿染色体异常的发生率随着双胎妊娠比例的增加也明显升高［1］。文献报道,双胎妊娠胎儿异常的比例为3.3%～3.8%［2-3］。与单胎相比,双胎妊娠的产前筛查和产前诊断更加复杂,产前咨询也更为困难。为了对双胎妊娠群体进行安全有效的产前筛查及诊断,降低双胎出生缺陷率,国家卫生和计划生育委员会公益性行业科研专项《常见高危胎儿诊治技术标准及规范的建立与优化》项目组于2017年制定了《双胎妊娠产前筛查与诊断技术规范》［4］。随着无创产前筛查技术在双胎中的应用以及分子遗传学诊断技术水平的发展,中国妇幼保健协会双胎妊娠专业委员会结合国内外研究进展更新了2017年的技术规范。 浏览更多请关注本刊微信公众号及当期杂志。     

产前系统超声筛查与胎儿染色体异常的关系

目的:探讨产前系统超声筛查中晚孕期胎儿结构异常对指导进行侵入性产前诊断的价值.方法:2008年1月至2009年6月对我院中晚孕期孕妇行系统超声及超声心动图筛查,发现胎儿异常时经产前咨询及孕妇知情同意后,进行侵入性产前检查即羊水或脐静脉穿刺,进行染色体核型分析,分析各种类型的超声异常表现与染色体异常发病风险的关系.结果:...     

Prenatal Screening for and Diagnosis of Aneuploidy in Twin Pregnancies

ObjectiveTo provide a Canadian consensus document with recommendations on prenatal screening for and diagnosis of fetal aneuploidy (e.g., Down syndrome and trisomy 18) in twin pregnancies.OptionsThe process of prenatal screening and diagnosis in twin pregnancies is complex. This document reviews the options available to pregnant women and the challenges specific to screening and diagnosis in a twin pregnancyOutcomesClinicians will be better informed about the accuracy of different screening options in twin pregnancies and about techniques of invasive prenatal diagnosis in twins.EvidencePubMed and Cochrane Database were searched for relevant English and French language articles published between 1985 and 2010, using appropriate controlled vocabulary and key words (aneuploidy, Down syndrome, trisomy, prenatal screening, genetic health risk, genetic health surveillance, prenatal diagnosis, twin gestation). Results were restricted to systematic reviews, randomized controlled trials, and relevant observational studies. Searches were updated on a regular basis and incorporated in the guideline to August 2010. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies The previous Society of Obstetricians and Gynaecologists of Canada guidelines regarding prenatal screening were also reviewed in developing this clinical practice guideline.ValuesThe quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table 1).Benefits, harms, and costsThere is a need for specific guidelines for prenatal screening and diagnosis in twins These guidelines should assist health care providers in the approach to this aspect of prenatal care of women with twin pregnancies.Summary StatementsFetal nuchal translucency combined with maternal age is an acceptable first trimester screening test for aneuploidies in twin pregnancies. (II-2)First trimester serum screening combined with nuchal translucency may be considered in twin pregnancies It provides some improvement over the performance of screening by nuchal translucency and maternal age by decreasing the false-positive rate. (II-3)Integrated screening with nuchal translucency plus first and second trimester serum screening is an option in twin pregnancies. Further prospective studies are required in this area, since it has not been validated in prospective studies in twins (III)Non-directive counselling is essential when invasive testing is offered (III)When chorionic villus sampling is performed in non-monochorionic multiple pregnancies, a combination of transabdominal and transcervical approaches or a transabdominal only approach appears to provide the best results to minimize the likelihood of sampling errors. (II-2)RecommendationsAll pregnant women in Canada, regardless of age, should be offered, through an informed counselling process, the option of a prenatal screening test for the most common clinically significant fetal aneuploidies. In addition, they should be offered a second trimester ultrasound for dating, assessment of fetal anatomy, and detection of multiples. (I-A)Counselling must be non-directive and must respect a woman's right to accept or decline any or all of the testing or options offered at any point in the process. (III-A)When non-invasive prenatal screening for aneuploidy is available, maternal age alone should not be an indication for invasive prenatal diagnosis in a twin pregnancy. (II-2A) If non-invasive prenatal screening is not available, invasive prenatal diagnosis in twins should be offered to women aged 35 and over. (II-2B)Chorionicity has a major impact on the prenatal screening process and should be determined by ultrasound in the first trimester of all twin pregnancies (II-2A)     

双胎妊娠胎儿染色体非整倍体产前筛查的研究进展

双胎妊娠胎儿染色体非整倍体疾病的发生率较单胎妊娠高,同时其筛查受到很多因素的影响。双胎妊娠的合子性质非常重要,直接影响风险率的计算模式,临床实践中多以妊娠早期绒毛膜性间接判断。目前双胎妊娠染色体非整倍体疾病筛查方案集中在妊娠早期胎儿颈部半透明层厚度(nuchal translucency,NT)筛查、妊娠早期联合筛查(NT+血清学筛查)、妊娠中期血清学筛查以及利用无创产前检测技术(noninvasive prenatal test,NIPT)进行胎儿染色体非整倍体疾病筛查。这些方案主要涉及染色体疾病中发病率较高的21-三体综合征和18-三体综合征。考虑到检出率、假阳性率以及经济学效应,妊娠早期联合筛查为目前双胎妊娠染色体非整倍体疾病筛查的主要方案,对近年来双胎妊娠染色体非整倍体产前筛查研究进展进行综述。     

Prenatal diagnosis in twin gestations

Twin gestations face an increased risk of structural abnormalities compared with singleton gestations, as well as an increased risk of aneuploidy. Accordingly, there is a need for accurate prenatal diagnosis of fetal genetic disorders and structural anomalies in twin gestations. Given the increased risk of congenital anomalies, a detailed sonographic survey of fetal anatomy is recommended in the early second trimester of twin gestations. In addition, fetal echocardiography should be considered in monochorionic twin gestations and in dichorionic twin pregnancies conceived using assisted reproductive technologies given the increased risk of congenital heart disease in these populations. Although first- and second-trimester aneuploidy screening in twin gestations is available, screening is less accurate than in singleton gestations. Invasive prenatal diagnosis in twin pregnancies is associated with a risk of pregnancy loss that is higher than the baseline risk of loss among twin gestations. Precise procedure-related loss rates in twin gestations undergoing chorionic villus sampling or amniocentesis, however, remain unclear because of methodological differences between published studies investigating diagnostic procedures in twins.     

Der nichtinvasive Pränataltest (NIPT) sinnvoll eingesetzt

The detection rate for Down’s syndrome using non-invasive prenatal testing (NIPT) is 99.2?%, which exceeds the rate for first trimester screening but does not fulfill the criteria for an adequate  diagnosis. The fetal examination by ultrasound during first trimester screening also allows a differentiated assessment of the fetus and is indispensable because congenital abnormalities are much more common than chromosome aberrations. Furthermore, assessment of additional sonographic markers during first trimester screening allows a precise classification into risk groups. The NIPT is most useful in the intermediate risk group. Correct interpretation of the results and counselling of the pregnant women are crucial for correct selection of further diagnostic steps.     

Trisomy 21. Second-trimester ultrasound

Not every aspect of sonographic examination reveals karyotypic abnormalities. Ultrasound examination of a fetus with trisomy 21 generally reveals normal amniotic fluid, normal placentation, and normal fetal growth. In addition, other chromosomal abnormalities have many of the same sonographic findings as Down syndrome, and many findings have a large overlap with phenotypically normal fetuses. The importance of second-trimester ultrasound screening for Down syndrome has remained great because of its ease of use and relative effectiveness. Trained sonographers can adjust the relative risk for trisomy 21 and alter the need for genetic amniocentesis. It is important that parents understand the limitations of a screening test and the risks and benefits of possible subsequent confirmatory testing. If a major structural abnormality is identified on ultrasound, karyotype determination should be considered. Nuchal thickness in the first or second trimester remains the most clinically useful marker for trisomy 21. The predictive value of all the markers depends on the population studied and can be modified by a host of biochemical markers and historical factors. If fetal karyotype analysis could be performed without sampling through the uterus, prenatal diagnosis could be offered to all pregnant women, and screening would be unnecessary. Despite its limitations, ultrasound will have an important role in prenatal diagnosis at least until isolating and testing fetal cells from maternal blood or other sources becomes practical and widely available. Whether used alone or in conjunction with additional biochemical or molecular serum markers, ultrasound is an important and powerful tool in prenatal genetic evaluation.     

Prenatal screening for chromosomal abnormalities in IVF patients that opted for preimplantation genetic screening/diagnosis (PGS/D): a need for revised algorithms in the era of personalized medicine

Obstetricians offer prenatal screening for most common chromosomal abnormalities to all pregnant women including those that had in vitro fertilization (IVF) and preimplantation genetic screening/diagnosis (PGS/D). We propose that free fetal DNA in maternal circulation together with the second trimester maternal serum alfa feto protein (MSAFP) and ultrasound imaging is the best prenatal screening test for chromosomal abnormalities and congenital anomalies in IVF-PGD/S patients because risk estimations from all other prenatal screening algorithms for chromosomal abnormalities depend heavily on maternal age which is irrelevant in PGS/D patients.     

Additional benefits of first trimester screening

The goal of first trimester screening for aneuploidy is to provide patients their risk assessment for fetal Down syndrome. Nonetheless, it has been noted that combined screening offers physicians and patients other important pregnancy information. For example, first trimester ultrasound results in accurate pregnancy dating and enables the early diagnosis of multiple gestations during the period when amnionicity and chorionicity is best discerned. It also detects a limited number of fetal anatomical abnormalities, affording patients time to make decisions regarding the management of their pregnancies. A cystic hygroma, one of the most powerful ultrasound markers for fetal aneuploidy, can be detected on first trimester ultrasound. An enlarged nuchal translucency may identify fetuses at risk for other adverse outcomes and for congenital heart defects. In addition, abnormal first trimester serum markers are associated with adverse pregnancy outcomes, and knowledge of these abnormalities may help with patient counseling and management.     

1p deletion syndrome: A prenatal diagnosis characterized by an abnormal 1st trimester combined screening test,yet a normal NIPT result

Objective

To present a case with prenatal diagnosis and cytogenetic characterization of 1p36 deletion syndrome whose first trimester combined testing is abnormal but a normal NIPT result.

9例多胎妊娠合并胎儿染色体异常患者的产前诊断和治疗

目的探讨多胎妊娠合并胎儿染色体异常的产前诊断方法及选择性减胎术定位方法。 方法选取2012年1月至2013年12月就诊于广州医科大学附属第三医院9例多胎妊娠合并胎儿染色体异常患者的临床资料,采用回顾性研究方法对其产前诊断方法、染色体异常情况、选择性减胎术的方法及妊娠结局进行分析。 结果9例患者中3例为三胎妊娠,6例为双胎妊娠。(1)产前诊断：①超声检查：9例患者早孕期行超声检查,均提示存在胎儿颈项透明层(nuchal translucency, NT)增厚,孕中期超声检查提示有6例患者存在胎儿结构异常,包括颈部囊肿、心脏异常、外生殖器畸形、足内翻、全身水肿等;②染色体检查：5例胎儿21-三体综合征,1例Turner综合征,1例染色体微缺失,1例染色体重复,1例双胎染色体异常。(2)治疗及妊娠结局：9例患者中7例患者行选择性减胎术治疗,1例流产,3例早产(新生儿均存在并发症),3例足月分娩(新生儿均未见异常);2例患者拒绝减胎,1例于孕中期自然流产,1例于孕35^＋周剖宫产分娩(1胎儿为21-三体综合征,另一胎儿为健康儿)。 结论多胎妊娠应注重早孕期染色体筛查,确诊宫内胎儿染色体异常的患者可在超声引导下行选择性减胎术治疗。     

双胎妊娠的孕期胎儿监护

因绒毛膜性不同,单绒双胎较双绒双胎胎儿的特殊并发症较多,围产儿预后较差。如何减少双胎妊娠母胎并发症,除了加强规范产前检查与健康指导,应在孕早期尽早超声监测明确绒毛膜性。孕早中期超声测量胎儿颈项透明层厚度以及系统超声筛查胎儿结构畸形,及早发现胎儿异常尤其是单绒双胎一些特有的特殊并发症,进行个体化超声动态监测、胎儿脐血流及胎心电子监护等了解胎儿宫内安危,及时发现异常及时干预,必要时终止妊娠,以降低出生缺陷,改善围产儿预后,保障母儿安全。