探讨早孕期唐氏综合征(DS)一站式临床风险评估(OSCAR)的临床应用价值。

选取2016年3月至2017年12月，于南宁市第二人民医院产科门诊接受早孕期OSCAR筛查的4 219例孕妇为研究对象。预产年龄为17.3～51.8岁，孕龄为11～13^＋6孕周。所有孕妇于孕龄为11～13^＋6孕周行胎儿颈项透明层(NT)测量。采用时间分辨免疫荧光分析法，检测孕妇血清妊娠相关蛋白(PAPP-A)和游离β-人绒毛膜促性腺激素(fβ-hCG)水平，将所测定的血清PAPP-A和fβ-hCG值输入产前筛查数据管理软件LifeCycle 4.0，软件自动计算血清fβ-hCG和PAPP-A水平中位数倍数(MoM)，并结合孕妇预产年龄、抽血当日体重、超声检查所提示孕龄、胎儿数等临床资料，计算胎儿罹患DS和18-三体综合征的风险。对于筛查结果高风险者建议进一步行羊水穿刺进行羊水细胞染色体核型分析；筛查结果为低风险者于中孕期再次行产前筛查。所有筛查高风险孕妇均跟踪随访至胎儿出生后42 d。本研究遵循的程序符合南宁市第二人民医院医学伦理委员会所制定的伦理学标准，得到该委员会批准(批准文号：20190924)。所有孕妇接受早孕期OSCAR筛查或介入性产前诊断前，均签署知情同意书。

①4 219例早孕期接受OSCAR筛查的孕妇中，DS高风险率为2.5%(103/4 219)，18-三体综合征高风险率为0.3%(11/4 219)。不同预产年龄段的DS和18-三体综合征高风险率比较，差异均有统计学意义(P<0.05)。进一步对DS高风险率进行比较结果显示，≥35岁孕妇DS高风险率均高于其他年龄段，并且差异亦均有统计学意义(P<0.05)。②NT值随孕龄增大呈逐渐增大的趋势，NT值MoM中位数也随着孕龄增大而增加。③孕妇血清PAPP-A水平中位数随孕龄增大而升高，血清fβ-hCG水平中位数随孕龄增大而降低。④4 219例早孕期进行OSCAR的孕妇中，筛查结果高风险者为113例(2.7%)，低风险者为4 106例(97.3%)。113例高风险孕妇中，同意行羊水穿刺或者绒毛穿刺术诊断的孕妇为42例(37.2%，42/113)，羊水细胞染色体核型分析诊断异常者为3例，其中，DS为2例(预产年龄分别为34岁和33岁)，13-三体综合征为1例(预产年龄为22岁)。⑤113例筛查高风险孕妇中，1例孕妇尚未进行产前诊断即出现胎儿停止生长发育，随后引产。进一步追踪筛查低风险孕妇结果发现，2例孕妇出现死胎进而引产的情况，该2例孕妇在产前筛查时PAPP-A MoM值异常，分别为0.35和0.28(正常参考值范围为0.5～2.5)。⑥对113例筛查高风险孕妇进行随访结果显示，成功随访为106例(93.8%)，失访7例(6.2%)。

早孕期DS OSCAR简便、经济，具有高性价比。此外，PAPP-A MoM值异常可作为不良妊娠结局的参考指标。

To explore the clinical application value of one-stop clinic for assessment of risk (OSCAR) for Down syndrome (DS) during frist trimester.

From March 2016 to December 2017, a total of 4 219 pregnant women who underwent OSCAR screening during frist trimester were selected into thisi study. The pre-delivery age was 17.3-51.8 years old and the gestational age was 11-13^{+ 6} weeks. All pregnant women were measured for nuchal translucency (NT) at gestational age of 11-13^{+ 6} weeks. Time-resolved immunofluorescence analysis was used to detect the serum pregnancy-related protein (PAPP-A) and free β-human chorionic gonadotropin (fβ-hCG) levels of pregnant women. The measured serum PAPP-A and fβ-hCG values were input into the prenatal screening data management software LifeCycle 4.0. The software automatically calculated the multiples of median of serum fβ-hCG and PAPP-A levels (MoM). The risks of DS and 18- trisomy syndrome were calculated in combination with the clinical data of pregnant women′s pre-delivery age, body weight on the day of blood drawing, gestational age indicated by ultrasound examination, number of fetuses, etc. For those with high risk of screening results, further amniocentesis is recommended for karyotype analysis of amniotic fluid cells. The screening result is that low-risk pregnant women will undergo prenatal screening again during second trimester. All high-risk pregnant women were followed up to 42 days after the birth of the fetus. The procedure followed in this study conforms to the ethical standards formulated by the Medical Ethics Committee of Nanning Second People′s Hospital. All pregnant women have signed an informed consent form before undergoing OSCAR screening or interventional prenatal diagnosis during the first trimester of pregnancy with the approval of the Committee (Approval No. 20190924).

① Among the 4 219 pregnant women screened by OSCAR during first trimester, the high risk rate of DS was 2.5% (103/4 219) and the high risk rate of 18-trisomy syndrome was 0.3% (11/4 219). The difference of DS and 18-trisomy syndrome in different pre-delivery age groups was statistically significant, respectively (P<0.05). Further comparison of DS high-risk rate shows that the DS high risk rate of pregnant women ≥35 years old was higher than that of other four different age ranges, and the differences were also statistically significant (P<0.05). ② NT value increased gradually with the increase of gestational age, and MoM of NT value also increased with the increase of gestational age. ③ The median serum PAPP-A level of pregnant women increased with the increase of pregnancy age, while the median serum fβ-hCG level decreased with the increase of pregnancy age. ④ Among the 4 219 pregnant women who underwent OSCAR in early pregnancy, 113 (2.7%) were at high risk and 4 106 (97.3%) were at low risk. Among 113 high-risk pregnant women, 42 (37.2%, 42/113) agreed to undergo amniocentesis or chorionic villus biopsy, and 3 were diagnosed as abnormal by karyotype analysis of amniotic fluid cells, of which 2 cases (34 and 33 years old, respectively) were DS and 1 case (22 years old) was 13-trisomy syndrome. ⑤ In 113 cases of screening high-risk pregnant women, 1 case of pregnant women had stopped growth and development before prenatal diagnosis, and then induced labor. Further follow-up screening of low-risk pregnant women found that 2 pregnant women had stillbirth and induced labor. The PAPP-A MoM values of the 2 pregnant women were abnormal during prenatal screening, which were 0.35 and 0.28, respectively (normal reference range was 0.5-2.5). ⑥ Follow-up results of 113 pregnant women screened for high-risk showed that 106 cases (93.8%) were successfully followed up and 7 cases (6.2%) were missed.

OSCAR for DS during first trimester is simple, economical and cost-effective. In addition, the abnormal PAPP-A MoM value can be used as a reference index for adverse pregnancy outcomes.