对高龄孕妇于孕中期行血清学二联指标筛查胎儿唐氏综合征的多中心前瞻性研究

Second trimester maternal serum screening for Down＇s syndrome in women of advanced maternal age： a multi-center prospective study

目的探讨高龄孕妇（至预产期时的年龄≥35岁）于孕中期行血清学二联指标筛查胎儿唐氏综合征的可行性。方法收集2004年5月至2006年9月期间在北京协和医院等11家医疗单位就诊的、孕周为14～20周“并同意接受产前筛查的单活胎孕妇行血清甲胎蛋白（AFP）和游离人绒毛膜促性腺激素B亚单位（13-hCG）二联指标检测，将二联指标测定值输入唐氏综合征风险计算软件，以1／270为高危切割值，≥1／270确定为唐氏综合征筛查阳性孕妇，对阳性孕妇进行遗传咨询，并记录所有孕妇的妊娠结局。11家医疗单位共有66132例孕妇纳入本研究。按预产期年龄不同分为高龄组（≥35岁）3610例（5．46％，3610／66132）和低龄组（〈35岁）62522例（94．54％，62522／66132）。分别计算两组孕妇的筛查检出率、假阳性率和阳性预测值。结果（1）两组孕妇的胎儿唐氏综合征筛查结果比较：高龄组孕妇中诊断胎儿唐氏综合征22例，低龄组孕妇中诊断胎儿唐氏综合征75例。以1／270为高危切割值进行筛查，共筛查出阳性孕妇5470例，从中诊断胎儿唐氏综合征91例。其中高龄组中阳性孕妇727例（13．3％，727／5470），胎儿唐氏综合征22例（24．2％，22／91）。低龄组中阳性孕妇4743例（86．7％，4743／5470），胎儿唐氏综合征69例（75．8％，69／91）。筛查阴性孕妇共60662例，从中诊断胎儿唐氏综合征6例。其中高龄组阴性孕妇2883例，未发现胎儿唐氏综合征；低龄组筛查阴性孕妇57779例，诊断胎儿唐氏综合征6例。在66132例孕妇中共发现胎儿唐氏综合征97例，在本研究人群中的胎儿唐氏综合征发生率为0．15％（97／66132）；高龄组中胎儿唐氏综合征发生率为0．61％（22／3610）；低龄组中胎儿唐氏综合征发生率为0．12％（75／62522）。（2）两组孕妇筛查检出率、假阳性率和阳性预测值比较：以1／270为高危切割值，采用孕中期行血清学二联指标对高龄组孕妇筛查胎儿唐氏综合征的检出率为100％，假阳性率为19．7％，阳性预测值为3．0％；低龄组孕妇筛查检出率为92．0％，假阳性率为7．5％，阳性预测值为1．5％，两组上述各指标间分别比较，差异均有统计学意义（P〈0．01）。结论对高龄孕妇行孕中期血清学二联指标筛查胎儿唐氏综合征，其筛查效率高于低龄孕妇，以1／270为高危切割值，可以有效地检出妊娠胎儿唐氏综合征的高危、高龄孕妇，降低羊膜腔穿刺率。建议对高龄孕妇在知情同意的基础上采用个体化的胎儿唐氏综合征产前筛查和诊断策略。

Objective To evaluate the performance characteristics of the second trimester double test for the detection of fetal Down＇s syndrome （DS） in women of advanced maternal age（AMA）. Methods We undertook a prospective nation-wide multi-centered study and chose alpha-fetoprotein （AFP） and free β-subunit of human chorionic gonadotrophin（ free β-hCG）as the serum markers. Between May 2004 and September 2006, 12 centers participated in the collection and analysis of maternal serum AFP and free β-hCG. Patients with an increased risk of DS （ ≥ 1/270） were offered genetic amniocentesis. Follow up of the outcome of all pregnancies was obtained. Patients were divided into two groups, the AMA group and the nonAMA group and the screening efficiency was evaluated in both groups. Results A total of 66 132 singleton pregnancies were included in the study, and there were 3610 （5.46%） AMA women. The median maternal age of AMA women was 36. 8years （35 -47 years）. At a cut-off of 1/270, in the AMA group, the number of positive cases screened was 727 and 22 cases of fetal DS were detected; the number of negative cases screened was 2883, and no fetal DS was found. In the non-AMA group, the number of positive cases screened was 4743 and 69 cases of fetal DS were detected; the number of negative cases screened was 57 779, and 6 cases of fetal DS were diagnosed postnatally. In AMA group, the detection rate （ DR）, false positive rate （FPR） and odds of being affected given a positive result （OAPR）were 100%, 19. 7% and 3.0% respectively. In the non-AMA group, the DR, FPR and OAPR were 92. 0%, 7.5% and 1.5% respectively. Conclusion The double-marker test using AFP and free 13-hCG is an effective screen strategy for second-trimester detection of Down syndrome in AMA women.