Objective: To evaluate the efficacy of non-invasive prenatal screening (NIPS) in the detection of fetal aneuploidies. Methods: Cell free DNA was sequenced in 5 566 pregnant women to identify the fetal aneuploidies in the First Affiliated Hospital of Zhengzhou University from January 1(st), 2015 to March 15(th), 2016. Among them, 5 230 (93.96%, 5 230/5 566) were singleton pregnancies and 336 (6.04%, 336/5 566) were twin pregnancies. In singleton pregnancies, 1 809 (34.59%, 1 809/5 230) were women with advanced maternal age, and 3 421 (65.41%, 3 421/5 230) were young women. The positive results of NIPS were validated by karyotyping through invasive procedures and neonatal outcomes were followed up by telephone. Results: Among the 5 566 women, 69 (1.24%, 69/5 566) got positive NIPS results, with 66 in singleton pregnancies and 3 in twin pregnancies. Two were monochorionic diamniotic twins and 1 was dichorionic twin pregnancy. The positive predictive value of NIPS for trisomy 21, 18 and 13 were 100.0%, 90.9% and 100.0%, and was 55.6% for sex chromosome aneuploidies. There was no false negative case found during the follow-up. In the advanced maternal age group and young women group, the prevalence rates of fetal chromosomal aneuploidies were 1.11%(20/1 809) and 0.94%(32/3 421), respectively. In the young women with soft markers in fetal ultrasound, the prevalence of fetal chromosomal aneuploidies was 1.44% (7/487), and in serum high risk women, it was 0.94% (7/747). In women with the serum screening risk with cut-off value, 0.89%(9/1 016) had fetal aneuploidies, and the prevalence was 0.77%(9/1 171) in volunteers. There was no statistically significant difference among these groups (P=0.636). Conclusions: There is no difference in the detection rate of fetal aneuploidies between high-risk women in serum screening and volunteers in NIPS. NIPS is more suitable as a first line screening test for women without fetal ultrasound abnormalities. It should be used carefully when there is ultrasound abnormalities.
目的： 分析无创产前筛查（NIPS）对胎儿染色体非整倍体检出的临床价值。 方法： 收集2015年1月1日至2016年3月15日于郑州大学第一附属医院就诊、并行NIPS的孕妇5 566例，其中单胎孕妇5 230例（93.96%，5 230/5 566），双胎孕妇336例（6.04%，336/5 566）。5 230例单胎孕妇中，高龄者（分娩年龄≥35岁）1 809例（34.59%，1 809/5 230），非高龄者3 421例（65.41%，3 421/5 230）。非高龄单胎孕妇包括超声软指标异常者、唐氏综合征血清学筛查高风险及临界者、自愿行NIPS者。NIPS结果为高风险（Z值≥3分或≤-3分）的孕妇，进行羊膜腔穿刺术或绒毛穿刺取样术确诊，并进行随访。 结果： 进行NIPS检测的孕妇中，69例（1.24%，69/5 566）的检测结果为高风险，其中66例为单胎者，3例为双胎者（2例为单绒毛膜性双胎，1例为双绒毛膜性双胎）。NIPS对诊断21三体、18三体、13三体的阳性预测值分别为100.0%、90.9%和100.0%，诊断性染色体非整倍体的阳性预测值为55.6%，经随访均无漏诊。NIPS结果为高风险的高龄单胎和非高龄单胎孕妇胎儿染色体非整倍体的发生率分别为1.11%（20/1 809）、0.94%（32/3 421）。3 421例非高龄单胎孕妇中，超声软指标异常者胎儿的染色体非整倍体发生率为1.44%（7/487），唐氏综合征血清学筛查为高风险孕妇的胎儿染色体非整倍体发生率为0.94%（7/747），唐氏综合征血清学筛查为临界风险孕妇的胎儿染色体非整倍体发生率为0.89%（9/1 016），自愿NIPS孕妇的胎儿染色体非整倍体发生率为0.77%（9/1 171），4者比较，差异无统计学意义（P=0.636）。 结论： 唐氏综合征血清学筛查提示高风险或临界风险的孕妇，其胎儿染色体非整倍体的NIPS检出率，与自愿行NIPS的孕妇相似；考虑到唐氏综合征血清学筛查漏检的风险，NIPS更适合作为胎儿超声无异常单胎孕妇的产前一线筛查方法；但对于胎儿超声异常且提示胎儿为染色体非整倍体者，NIPS应慎重应用。.
Keywords: Aneuploidy; Chromosome aberrations; Down syndrome; High-throughput nucleotide sequencing; Prenatal diagnosis.