探讨中孕期唐氏综合征(DS)血清学筛查在高龄孕妇中的应用价值。

选取2009年1月至2014年12月于四川大学华西第二医院妇产科产前诊断中心接受中孕期DS血清学筛查的1 571例高龄孕妇(预产年龄≥35岁)，以及2012年1～12月于本院妇产科产前诊断中心接受中孕期DS血清学筛查的10 881例低龄孕妇(预产年龄<35岁)为研究对象，分别纳入高龄组(n＝1 571)和低龄组(n＝10 881)。本研究纳入标准：妊娠期妇女，孕龄为14～20^＋6孕周，单胎妊娠，自愿接受中孕期DS血清学筛查。排除标准：有染色体异常和先天性畸形家族史者，妊娠期内合并内外科疾病者，双胎或多胎妊娠者，以及糖尿病患者。采用血清游离β-人绒毛膜促性腺激素(hCG)、甲胎蛋白(AFP)和游离雌三醇(uE₃)DS三联筛查法对两组孕妇进行DS筛查，设定DS血清学高风险临界值为l/270。对DS血清学筛查风险值≥l/270的DS血清学筛查高风险孕妇，均建议行羊膜腔穿刺染色体检查，以确诊胎儿是否为DS；对未接受羊膜腔穿刺染色体检查的孕妇，采用电话随访方式随访其妊娠结局。分别计算两组孕妇DS血清学筛查的假阳性率和筛查效率，并进行统计学比较。两组受试对象的孕龄和体重等比较，差异均无统计学意义(P>0.05)。本研究遵循的程序符合四川大学华西第二医院人体试验委员会制定的伦理学标准，得到该委员会批准，DS血清学产前筛查前均征得受试对象的知情同意。

①高龄组1 571例孕妇中，DS血清学筛查高风险孕妇为121例，4例胎儿最终被确诊为DS；DS血清学筛查低风险孕妇为1 450例，未发现DS胎儿。低龄组10 881例孕妇中，DS血清学筛查高风险孕妇为759例，6例胎儿最终被确诊为DS；DS血清学筛查低风险孕妇为10 122例，1例胎儿最终被确诊为DS，为DS血清学筛查假阴性病例。②高龄组孕妇DS血清学筛查假阳性率为7.4%(117/1 571)，低龄组为6.9%(753/10 881)，二者筛查假阳性率比较，差异无统计学意义(χ²＝0.587，P＝0.444)。③高龄组孕妇DS血清学筛查效率为3.3%(4/121)，显著高于低龄组的0.8%(6/759)，并且差异有统计学意义(χ²＝3.870，P＝0.049)。

对高龄孕妇进行中孕期DS血清学三联筛查，其筛查效率高于低龄孕妇，可在高龄孕妇中较有效地检出胎儿DS，降低产前有创的羊膜腔穿刺诊断率。

To evaluate the value of second trimester serological screening of Down syndrome (DS) in pregnant women with advanced age.

From January 2009 to December 2014, a total of 1 571 cases of pregnant women with advanced age (expected age of delivery≥35 years old) who received second trimester serological screening for DS in Department of Prenatal Diagnosis of Obstetrics and Gynecology, West China Second University Hospital were enrolled as advanced age group (n=1 571). From January to December 2012, a total of 10 881 cases of young pregnant women (expected age of delivery<35 years old) who received second trimester serological screening of DS in the same hospital were chose as young group (n=10 881). The inclusion criteria for subjects in this research were as follows: pregnant women, gestational age of 14 to 20^{+ 6} weeks, singleton pregnancy, voluntary to do second trimester DS serological screening. The exclusion criteria for subjects: bearing a family history of congenital malformations or chromosomal abnormalities, associated with other internal or surgical diseases, bigeminal or multiple pregnancy and patients with diabetes. Three second trimester maternal serum screening markers, free β-human chorionic gonadotrophin (β-hCG), alpha fetoprotein (AFP) and unconjugated estriol (uE₃) were used for DS serological screening. Patients with an increased risk of DS (≥l/270) were offered genetic amniocentesis to ensure whether the fetus was DS or not, and the pregnancy outcomes of other pregnant women who didn't received genetic amniocentesis were obtained by telephone follow-up. The false positive rate and screening efficiency of DS serological screening were evaluated in both two groups and were compared by statistical methods. The study protocol was approved by the Ethical Review Board of Investigation in West China Second University Hospital. Informed consent was obtained from each patient before receiving second trimester DS screening. There were no statistical differences of gestational age and weight between groups (P>0.05).

①Among 1 571 cases of pregnant women in advanced age group, 121 cases were in high-risk of DS serological screening, and 4 cases were diagnosed as DS; 1 450 cases were in low-risk of DS serological screening, and no fetal DS was found. Among 10 881 cases of pregnant women in young group, 759 cases were in high-risk of DS serological screening, and 6 cases were diagnosed as DS; 10 122 cases were in low-risk of DS serological screening, and 1 case were diagnosed as DS postnatally. ②In advanced age group, the false positive rate of DS serological screening was 7.4% (117/1 571), the young group was 6.9% (753/10 881), and the difference was not statistically significant (χ²=0.587, P=0.444). ③In advanced age group, DS serological screening efficiency was 3.3% (4/121), which was significantly higher than that of young group (0.8%, 6/759), and the difference was statistically significant (χ²=3.870, P=0.049).

The three-marker (β-hCG, AFP and uE₃) test is an effective screen strategy for second trimester serological screening of DS in pregnant women with advanced age. It can reduce the rate of genetic amniocentesis.