双胎妊娠的产前筛查和产前诊断

据统计，双胎妊娠约占总妊娠的1％～1．2％左右。双胎分为双卵双胎和单卵双胎，其中单卵双胎约占30％。双卵双胎为双绒毛膜双胎，其胎盘间没有血管吻合；单卵双胎分为双绒毛膜双羊膜、单绒毛膜双羊膜、单绒毛膜单羊膜、联体双胎，其胎盘间血管吻合发生率达85％以上，约15％的单绒毛膜双胎将发展为双胎输血综合征（twin-twin transfusion syndrome，TTTS）。由于双胎的自然流产率、早产率及围产儿死亡率都明显高于单胎，而绒毛膜特性又是影响双胎结局的最主要因素，单绒毛膜双胎的围产期死亡率是双绒毛膜双胎的3～5倍，所以双胎绒毛膜性质的诊断至关重要，也是讨论双胎产前诊断的前提。     

双胎染色体非整倍体的产前筛查

妊娠物染色体中,不少于8%是非整倍体。常见的染色体非整倍体包括21-三体、18-三体、13-三体等。这些非整倍体导致了50%的妊娠早期流产和5%～7%的死产与新生儿死亡。近年来,由于妇女生育年龄普遍提高、辅助生殖技术的普及与不规范的卵巢刺     

无创产前筛查在双胎妊娠染色体非整倍体筛查中的应用及胎儿游离DNA浓度分析

目的 评估无创产前筛查(non-invasive prenatal testing, NIPT)在双胎妊娠染色体非整倍体的应用价值,并对胎儿游离DNA浓度进行分析。方法 收集2018年1月至2023年5月在广州市花都区妇幼保健院接受NIPT检测的双胎样本617例(辅助生殖双胎284例,自然妊娠双胎333例)为研究对象,同期12688例单胎妊娠样本作为对照,采用高通量测序方法进行检测,对染色体非整倍体高风险样本行核型分析,根据Y染色体唯一比对条数对男胎进行胎儿游离DNA浓度计算,使用基于浅深度的母亲血浆DNA测序方法(SeqFF)对女胎进行胎儿游离DNA浓度计算。结果 双胎妊娠检出2例T21和1例T18,未检出T13,T21、T18的阳性预测值分别为100%、0,阴性预测值均为100%;单胎妊娠T21、T18、T13的阳性预测值分别为88.89%、45.45%、25%,阴性预测值均为100%。双胎妊娠胎儿游离DNA浓度为10.48%,较单胎妊娠(11.35%)稍低;双胎妊娠首次建库成功率为99.03%,较单胎妊娠(99.99%)低,差异有统计学意义(χ²=104.1...     

双胎妊娠染色体异常的产前筛查及产前诊断

双胎妊娠发生胎儿畸形、染色体异常的风险较单胎妊娠高。近年来双胎妊娠发生率和高龄产妇数量不断增加,双胎妊娠的早期筛查以及产前诊断十分重要。早孕期,颈项透明层(nuchal translucency,NT)超声筛查是重要手段,不建议单独使用血清学筛查;中孕期超声结构筛查对检出胎儿结构异常有一定意义。无创产前基因检测技术的发展,对降低侵入性产前诊断的风险有重要意义,但由于目前临床证据尚不充分,双胎妊娠行无创基因检测仍需谨慎。     

双胎妊娠产前筛查与诊断技术规范(2017)

中国是出生缺陷高发国之一,出生缺陷发生率约为5.6%,每年新增出生缺陷数约90万例,出生缺陷儿给社会和家庭带来了巨大的经济负担和精神压力[1]。近年来,随着我国计划生育政策的变化及辅助生殖技术的发展,双胎妊娠发生率逐年升高。双胎妊娠死亡率、患病率、流产率、胎儿畸     

双胎妊娠产前筛查及产前诊断——一个新的挑战

近年来,双胎妊娠的发生率逐年升高。美国近20余年来双胎妊娠的发生率上升了77％,1980年为18．9／1000,2006年上升至32．1／1000。其增长原因可能与生育年龄的延迟和辅助生殖技术的广泛应用有关。美国从1990年至2002年,35-39岁的孕妇增长了31％,并且30％～50％的双胎妊娠是源于辅助生殖技术。     

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。     

双胎妊娠中无创产前检测的胎儿游离DNA浓度特征及检测失败原因分析

目的 分析双胎妊娠中无创产前筛查检测的胎儿游离DNA浓度及检测失败原因,探讨无创产前基因检测(noninvasive prenatal testing, NIPT)在双胎妊娠中的筛查效果和临床价值。方法 选择2017年11月至2023年6月接受NIPT产前筛查的1685例双胎孕妇和109784例单胎孕妇作为研究对象,对行NIPT检测孕妇的血浆中胎儿游离DNA(cell free fetal DNA,cffDNA)浓度情况和检测失败原因及双胎妊娠对三大目标染色体的筛查效果进行分析。结果 1685例双胎妊娠孕妇中NIPT检测成功1669例,检测成功率为99.05%,检测失败16例,检测失败率为0.95%,cffDNA浓度均在0.84%～41.22%,平均循环游离DNA(cffDNA)浓度为(10.30±4.75)%。109784单胎妊娠孕妇NIPT检测成功109335例,检测成功率为99.59%,检测失败总计有449例,检测失败率为0.41%,cffDNA浓度均在0.94%～49.83%,平均cffDNA浓度为(9.52±3.92)%。双胎妊娠孕妇中有11例检测结果提示高风险,筛查阳性率为...     

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。     

染色体微阵列分析在无创产前筛查非整倍体高风险中的应用价值

目的:探讨染色体微阵列分析(CMA)技术在无创产前筛查(NIPT)提示非整倍体高风险胎儿的产前诊断中的应用价值。方法:241例NIPT提示胎儿染色体非整倍体高风险的孕妇,经羊膜腔或绒毛穿刺获取胎儿细胞,进行CMA分析。对于NIPT提示21-三体和性染色体非整倍体高风险的孕妇根据筛查原因(高龄筛查组、唐筛异常或超声软指标异常组、非高龄筛查组)进行组间NIPT阳性预测值的比较,并对CMA检测提示有染色体拷贝数变异(CNV)的病例进行致病性分析。结果:NIPT对于染色体非整倍体总的阳性预测值为76.3%。NIPT对于21-三体、18-三体、13-三体和性染色体非整倍体的阳性预测值分别为95.0%、88.8%、75.0%和53.3%。经CMA分析确认,在101例NIPT提示21-三体高风险病例中,以高龄筛查组阳性预测值最高(100.0%),3组间比较,差异有统计学意义(P=0.001)。在90例NIPT提示性染色体非整倍体高风险病例中,仍以高龄筛查组阳性预测值最高(61.9%),3组间比较,差异有统计学意义(P=0.002)。12例NIPT提示染色体非整倍体高风险经CMA检测存在CNV。结论:...     

双胎妊娠产前诊断取样技术评估

产前诊断取样技术对双胎染色体异常的精准诊断必不可少。文章从双胎介入性产前诊断的标识系统、操作要点、术后相关风险及取样技术间的优劣对比等方面进行综述,为临床医生相关咨询及处理提供参考。     

Non-invasive prenatal screening of fetal Down syndrome by maternal plasma DNA sequencing in twin pregnancies

Non-invasive prenatal screening for fetal Down syndrome (NIFTY) by maternal plasma sequencing was performed in 12 subjects with twin pregnancies, including 11 with normal fetuses and 1 with discordant fetal Trisomy 21. For every sample, it was processed, sequenced and reported as soon as it was collected as other clinical samples for singleton pregnancies. The NIFTY test was negative in the 11 pregnancies carried normal fetuses, and was positive (high risk) in the case with discordant fetal Trisomy 21. The sensitivity and specificity were both 100%. This small case series suggested the NIFTY as a screening test for fetal Trisomy 21 is feasible in twin pregnancies.     

Prenatal screening for common aneuploides

Down syndrome screening has been available within clinical practice for over 50 years within which time significant innovation and exciting new advances have improved the accuracy, safety, and choice for women who are considering antenatal screening for Down syndrome. The UK National Screening Committee is responsible for setting the national standards regarding screening and it has steadily and consistently directed and facilitated an increase in the detection rate whilst minimising the screen positive rate. This has reduced the number of false positive results and consequently the number of invasive diagnostic procedures and their related miscarriages. Non-invasive pre-natal testing (NIPT) using cell free DNA is a rapidly evolving field and it will soon be incorporated into the existing NHS antenatal screening programme for aneuploidy. It will be offered to women who receive a ‘high risk’ result following current screening methods (combined test or quadruple test), and will further reduce the number of invasive tests performed, whilst maintaining current detection rates.     

复杂性双胎妊娠超声诊断及孕期监测

复杂性双胎严重影响围产儿出生质量及预后,而利用超声对复杂性双胎进行诊断及评估既安全又可靠。如何在众多双胎妊娠中识别、诊断复杂性双胎,并对其进行有效孕期监护和及时处理,是改善复杂性双胎妊娠的预后及降低缺陷出生的关键所在。     

Prenatal diagnosis and outcome of congenital cytomegalovirus infection in twin pregnancies

OBJECTIVE: To study the outcome of 20 twin pregnancies with evidence of primary or recurrent cytomegalovirus (CMV) infection during pregnancy. DESIGN: Observational study. SETTING: Two tertiary perinatal departments in Israel. POPULATION: Twenty women with twin pregnancies who were referred because of serologic investigation indicating CMV infection. Seventeen women had evidence of primary CMV infection, and three women appeared to have recurrent CMV infection. METHODS: Prenatal diagnosis was made by amniocentesis of both sacs after 21 weeks of gestation. CMV isolation was performed by culture on fibroblasts, shell vial technique and polymerase chain reaction (PCR) amplification of CMV DNA. After birth, the neonatal urine and saliva were cultured for CMV. MAIN OUTCOME MEASURES: Intrauterine CMV infection defined as positive PCR at amniotic fluid analysis and congenital CMV infection defined as positive CMV cultures after birth. RESULTS: Except for one, all women underwent amniocentesis of both gestational sacs. In 14 (70%) women, no evidence of vertical transmission to any of the 28 fetuses was found and none of the newborns had evidence of congenital CMV infection. Intrauterine infection was detected by amniocentesis in five women and by ultrasound findings with positive maternal serology in one. In three women, CMV was detected in only one amniotic sac. In five of our six total cases, both twins were found to have congenital CMV infection at birth, all of whom had dichorionic-diamniotic placentation, three fused and two separate. CONCLUSIONS: In twin gestations, as in singletons, intrauterine and congenital CMV infection occurs in about 30% of women with primary or recurrent infection. The placenta type did not predict if one or both twins would be infected. Our data do not exclude the possibility that intrauterine transmission of the virus from one fetus to the other can occur.     

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。     

Prenatal screening for fetal aneuploidies with cell-free DNA in the general pregnancy population: a cost-effectiveness analysis

Objective: To estimate the cost-effectiveness of fetal aneuploidy screening in the general pregnancy population using non-invasive prenatal testing (NIPT) as compared to first trimester combined screening (FTS) with serum markers and NT ultrasound.

Methods: Using a decision-analytic model, we estimated the number of fetal T21, T18, and T13 cases identified prenatally, the number of invasive procedures performed, corresponding normal fetus losses, and costs of screening using FTS or NIPT with cell-free DNA (cfDNA). Modeling was based on a 4 million pregnant women cohort, which represents annual births in the U.S.

Results: For the general pregnancy population, NIPT identified 15% more trisomy cases, reduced invasive procedures by 88%, and reduced iatrogenic fetal loss by 94% as compared to FTS. The cost per trisomy case identified with FTS was $497?909. At a NIPT unit, cost of $453 and below, there were cost savings as compared to FTS. Accounting for additional trisomy cases identified by NIPT, a NIPT unit cost of $665 provided the same per trisomy cost as that of FTS.

Conclusions: NIPT in the general pregnancy population leads to more prenatal identification of fetal trisomy cases as compared to FTS and is more economical at a NIPT unit cost of $453.