探讨唐氏综合征(DS)产前筛查结果为极高风险孕妇(DS风险值≥1/20)的妊娠结局，并与DS产前筛查结果为普通高风险孕妇的妊娠结局进行比较，旨在了解DS产前筛查效力。

选择2011年1月1日至2015年12月30日，于广州市妇女儿童医疗中心接受DS产前筛查，并且DS风险值≥1/20的167例DS产前筛查结果为极高风险的单胎妊娠孕妇为研究对象。根据孕妇接受DS产前筛查时孕龄，将其分为早孕期DS极高风险组(n＝75)和中孕期DS极高风险组(n＝92)。选择同期因DS产前筛查结果为高风险(1/270≤DS风险值<1/20，或者18-三体综合征风险值≥1/350)，而在本院接受介入性产前诊断的6 826例单胎妊娠孕妇，纳入对照组。对早孕期孕妇的DS筛查，采用DS一站式临床风险评估(OSCAR)方法，即胎儿颈项透明层(NT)超声检查联合孕妇血清妊娠相关蛋白A(PAPP-A)及游离β-人绒毛膜促性腺激素(f β-hCG)水平筛查；对中孕期孕妇的DS筛查，采用孕妇血清学三联筛查方法，即孕妇血清甲胎蛋白(AFP)、f β-hCG和游离雌三醇(uE₃)水平联合筛查。随访和比较3组孕妇的妊娠结局。采用χ²检验，对3组孕妇正常分娩率与胎儿染色体异常、胎儿超声结构异常、其他不良妊娠结局发生率进行比较，采用Fisher确切概率法进行两两比较，并调整检验水准(α′＝0.017)。本研究遵循的程序符合2013年修订的《世界医学协会赫尔辛基宣言》要求。所有孕妇接受DS产前筛查或介入性产前诊断前，均签署知情同意书。3组孕妇年龄等一般临床资料比较，差异均无统计学意义(P>0.05)。

①早孕期DS极高风险组、中孕期DS极高风险组、对照组孕妇的正常分娩率分别为48.0%(36/75)、71.7%(66/92)、96.0%(6 552/6 826)，胎儿染色体异常发生率分别为45.9%(28/61)、22.2%(12/54)、2.4%(160/6 826)，胎儿超声结构异常发生率分别为12.0%(9/75)、5.4%(5/92)、0.9%(64/6 826)，其他不良妊娠结局发生率分别为2.7%(2/75)、9.8%(9/92)、0.7%(50/6 826)。3组孕妇正常分娩率及胎儿染色体异常、胎儿超声结构异常、其他不良妊娠结局发生率分别总体比较，差异均有统计学意义(χ²＝481.120、482.655、98.080、88.808，P<0.001)。进一步进行两两比较的结果显示，早、中孕期DS极高风险组正常分娩率，均显著低于对照组，而胎儿染色体异常、胎儿超声结构异常、其他不良妊娠结局发生率，则均显著高于对照组；早孕期DS极高风险组正常分娩率，显著低于中孕期DS极高风险组，而胎儿染色体异常发生率，则显著高于中孕期DS极高风险组，并且差异均有统计学意义(P<0.017)。②早孕期DS极高风险组75例孕妇中，68例(90.7%)检出胎儿NT增厚。其中，26例(38.2%，26/68)检出胎儿染色体异常，9例(13.2%，9/68)检出胎儿超声结构异常，2例(2.9%，2/68)发生自然流产，31例(45.6%，31/68)正常分娩。

DS产前筛查结果为极高风险孕妇的不良妊娠结局，如胎儿染色体异常、胎儿超声结构异常、自然流产、死胎、早产等发生风险，均较筛查结果为普通高风险孕妇高。因为本研究仅为回顾性研究，早孕期OSCAR筛查法对于DS产前筛查的效果，是否优于中孕期血清学筛查效果，则尚需要大样本、多中心、前瞻性研究结果证实。

To investigate the pregnant outcomes in women with very high risk of Down syndrome (DS) screening (the risk of DS ≥1/20), and to compare the differences of pregnant outcomes between pregnant women with very high risk of DS and with general high risk of DS, and explore the screening efficiency of DS prenatal screening.

From January 1, 2011 to December 30, 2015, a total of 167 singleton pregnant women with very high risk of DS screening (the risk of DS ≥1/20) in Guangzhou Women and Children′s Medical Center were selected as research subjects. According to the gestational age of pregnant women undergoing DS prenatal screening, they were divided into first trimester pregnancy with very high risk of DS group (n=75) and second trimester pregnancy with very high risk of DS group (n=92). And 6 826 cases of singleton pregnant women who received invasive prenatal diagnosis in our hospital due to high risk of prenatal screening (1/270≤ DS risk value <1/20 or 18-trisomy syndrome risk value ≥1/350) during the same period were selected as control group. The first trimester DS screening method was one-stop clinic for assessment of risk (OSCAR) which was the combination of ultrasound examination of fetal nuchal translucency (NT) and screening of maternal serum pregnancy-associated protein A (PAPP-A) and free β-human chorionic gonadotropin (f β-hCG). While the second trimester DS screening method was triple serological screening which included the screening of maternal serum alpha fetoprotein (AFP), f β-hCG and unconjugated oestriol (uE₃). Pregnancy outcomes of the three groups were followed up and compared. Chi-square test was used to compare the normal delivery rate, and incidences of fetal chromosomal abnormalities, fetal ultrasound structural abnormalities, and other adverse pregnancy outcomes among the three groups. Further comparisons were conducted by Fisher′s exact probability method with adjustment of the test level (α′=0.017). The study was in accordance with World Medical Association Declaration of Helsinki revised in 2013. Informed consent was obtained from all pregnant women before receiving DS prenatal screening or interventional prenatal diagnosis. There were no significant differences in the age and other general clinical data among the three groups (P>0.05).

①Among the first trimester pregnancy with very high risk of DS group, second trimester pregnancy with very high risk of DS group, and control group, the normal delivery rates were 48.0% (36/75), 71.7% (66/92), 96.0% (6 552/6 826), respectively, and the incidences of fetal chromosomal abnormalities were 45.9% (28/61), 22.2% (12/54), 2.4% (160/6 826), respectively, and the incidences of fetal ultrasound structural abnormalities were 12.0% (9/75), 5.4% (5/92), 0.9% (64/6 826), respectively, and the incidences of other adverse pregnancy outcomes were 2.7% (2/75), 9.8% (9/92), 0.7% (50/6 826), respectively. There were statistical differences among the three groups in the normal delivery rate, and incidences of fetal chromosomal abnormalities, fetal ultrasound structural abnormalities and other adverse pregnancy outcomes (χ²=481.120, 482.655, 98.080, 88.808; all P<0.001). Further comparisons results showed that the normal delivery rate of the first trimester pregnancy with very high risk of DS group and second trimester pregnancy with very high risk of DS group was significantly lower than that of control group, and the incidences of fetal chromosomal abnormalities, fetal ultrasound structural abnormalities, and other adverse pregnancy outcomes were significantly higher than those of control group; and the normal delivery rate of the first trimester pregnancy with very high risk of DS group was lower than that of the second trimester pregnancy with very high risk of DS group, while the incidence of fetal chromosomal abnormalities was higher than that of the second trimester pregnancy with very high risk of DS group, and all the differences were statistically significant (P<0.017). ②Among the 75 pregnant women in first trimester pregnancy with very high risk of DS group, 68 cases (90.7%) developed fetal NT thickening. Among these 68 cases of pregnant women, fetal chromosomal abnormalities were detected in 26 cases (38.2%, 26/68), fetal ultrasound structural abnormalities were detected in 9 cases (13.2%, 9/68), spontaneous abortion occurred in 2 cases (2.9%, 2/68), and 31 cases (45.6%, 31/68) had normal delivery.

The risk of adverse pregnancy outcomes in women with very high risk of DS are significantly higher than those with general high risk of DS, such as fetal chromosomal abnormalities, fetal ultrasound structural abnormalities, spontaneous abortion, dead fetus and premature delivery. As this study is just a retrospective study, whether the screening efficiency of OSCAR method in first trimester pregnancy is better than that of serological screening method in the second trimester, it still needs to be confirmed by large-sample, multi-center, prospective studies.