中孕期胎儿染色体异常高危孕妇羊水细胞胎儿染色体核型及介入性产前诊断指征的大样本分析

Fetal karyotype of amniotic fluid cells and interventional prenatal diagnosis indications of pregnant women in the second trimester with high risk of fetal chromosome abnormality:a large sample study

目的探讨中孕期胎儿染色体异常(FCA)高危孕妇羊水细胞胎儿染色体核型(FK)及其介入性产前诊断(IPD)指征。方法选择2014—2018年,在四川大学华西第二医院产前诊断中心进行羊膜腔穿刺术羊水细胞FK检测的63581例FCA高危孕妇(孕龄为19~27+6孕周)为研究对象。回顾性分析孕妇不同IPD指征及其胎儿染色体核型异常(FKA)检测结果。本研究遵循的程序符合四川大学华西第二医院伦理委员会所制定的伦理学标准,并通过该伦理委员会批准[审批文号:医学科研2019伦审批第(077)号]。结果①本组63581例中孕期孕妇的FKA检出率为3.13%(1989/63581)。这63581例孕妇的IPD指征分别为高龄(预产期年龄≥35岁)(25648例)、血清学筛查高风险(29009例)、无创产前筛查(NIPT)高风险(333例)、夫妇一方为染色体异常携带者(603例)、超声筛查发现胎儿结构异常及超声软指标异常(2647例)、异常儿生育史(1546例)、于外院进行羊水细胞FK分析结果异常者(7例)、孕妇智力低下及合并智力低下家族史(149例)、孕妇早孕期有害物质接触史(1400例)、其他(2239例),FKA检出率分别为3.26%(836/25648)、2.04%(593/29009)、65.17%(217/333)、34.33%(207/603)、3.51%(93/2647)、1.68%(26/1546)、85.71%(6/7)、4.03%(6/149)、0.14%(2/1400)、0.13%(3/2239)。②351例孕妇的IPD指征为超声筛查发现胎儿结构异常中,IPD指征为胎儿淋巴水囊瘤、皮肤水肿的FKA检出率最高,为26.09%(6/23)。2296例孕妇的IPD指征为胎儿超声软指标异常中,IPD指征为胎儿颈项透明层(NT)值≥2.5 mm的FKA检出率最高,为7.74%(66/853)。结论孕妇高龄、血清学筛查高风险、NIPT高风险、夫妇一方为染色体异常携带者、超声筛查发现胎儿结构异常及超声软指标异常等,均为中孕期孕妇FCA的IPD指征,孕妇IPD指征类型不同,FCA风险不同。羊膜腔穿刺术羊水细胞FK检测,可预测有IPD指征孕妇的妊娠结局,为降低FKA出生率提供参考。

Objective To explore fetal karyotype(FK)of amniotic fluid cells and interventional prenatal diagnosis(IPD)indications of pregnant women in the second trimester with high risk of fetal chromosome abnormality(FCA).Methods A total of 63581 pregnant women in the second trimester(19 to 27+6 gestational weeks)with high risk of FCA who received amniocentesis for FK detection of amniotic fluid cells in Department of Prenatal Diagnosis Center of West China Second University Hospital,Sichuan University from 2014 to 2018 were selected as research subjects.Results of different indications of IPD and fetal karyotype abnormality(FKA)in pregnant women were analyzed retrospectively.The procedures followed in this study complied with the ethical standards of Ethics Committee of West China Second University Hospital,Sichuan University and were approved by the Ethics Committee(Approval No.077 for Medical Research 2019).Results①Among 63581 pregnant women in the second trimester,detection rate of FKA was 3.13%(1989/63581).IPD indications in 63581 pregnant women included:25648 cases of advanced age(age at date of confinement≥35 years old),29009 cases were high risk of serological screening,333 cases were high risk of noninvasive prenatal testing(NIPT),603 cases were carriers of chromosomal abnormalities in one of the couple,2647 cases with fetal structure abnormality and abnormal soft index in ultrasound screening,1546 cases were with birth defect history,7 cases were with abnormal results in FK analysis of amniotic fluid cells in other hospitals,149 cases were pregnant women with mental retardation or family history of mental retardation,1400 cases with a history of adverse exposure to harmful substances during the first trimester,and 2239 cases were with other indications.And detection rates of FKA in pregnant women with the above IPD indications were 3.26%(836/25648),2.04%(593/29009),65.17%(217/333),34.33%(207/603),3.51%(93/2647),1.68%(26/1546),85.71%(6/7),4.03%(6/149),0.14%(2/1400),and 0.13%(3/2239),respectively.②Among 351 pregnant women whose IPD indications were fetal structural abnormalities in ultrasound screening,the detection rate of FKA in pregnant women with fetal lymphatic cystoma and cutaneous edema was the highest,which was 26.09%(6/23).Among 2296 pregnant women whose IPD indications were abnormal fetal ultrasound soft indexes,the detection rate of FKA in pregnant women with fetal nuchal translucency(NT)value≥2.5 mm was the highest,which was 7.74%(66/853).Conclusions Advanced age,high risk of serological screening and NIPT,carrier of chromosomal abnormalities in one of the couple,fetal structure abnormality and abnormal soft index in ultrasound screening all are indications of IPD for FCA of pregnant women in the second trimester,and the risk of FCA varies with different types of IPD indications.Amniotic fluid cells FK detection by amniocentesis can assess the pregnancy outcomes of pregnant women with IPD indications and provide a reference for reducing birth rate of FKA.