妊娠中期血清学三联筛查指标异常对孕妇发生不良妊娠结局的预测价值

Predictive value of abnormal second-trimester maternal serum triple screening markers for adverse pregnancy outcomes

目的 探讨孕中期孕妇血清学三联筛查指标MoM值异常对不良妊娠结局的预测价值.方法 收集2010年7月-2013年1月吉林大学第一医院生殖医学中心行血清学三联筛查的孕15～20＋6周单胎孕妇16 000例.采用时间分辨荧光免疫分析仪检测孕妇血清中AFP、游离β-hCG（F-β-hCG）、游离雌三醇（uE3）水平,应用LifeCycle 3.2软件计算其MoM值和风险值,其中21三体和18三体分别以＞ 1/270和＞1/350为高风险,开放性神经管缺陷（ONTD）以AFP MoM值＞2.5为高风险;各指标检测结果分别以AFP MoM值＞2.0、F-β-hCG MoM值＞2.0为异常升高,uE3 MoM值＜0.5为异常降低.对筛查高风险孕妇进行胎儿染色体核型分析,产后随访;对发生不良妊娠结局孕妇的血清学三联筛查指标的MoM值与健康孕妇进行比较.结果 （1）AFP、F-β-hCG和uE3的MoM值中位数分别为0.91、0.94和1.05,不同孕周孕妇血清学三联筛查各指标MoM值中位数比较,差异均无统计学意义（P＞0.05）.孕妇预产年龄≤35岁14 972例,21三体、18三体和ONTD血清学筛查高风险发生率分别为4.03％（603/14 972）、0.36％（54/14 972）和0.29％（44/14 972）;孕妇预产年龄＞35岁1 028例,其中21三体、18三体和ONTD血清学三联筛查高风险发生率分别为24.51％（252/1 028）、1.95％（20/1 028）和0.78％（8/1 028）;两者孕妇血清学三联筛查高风险发生率比较,差异有统计学意义（P＜0.05）.（2）经产前诊断核型分析和产后随访发现,筛查高风险孕妇中诊断21三体9例、18三体1例、ONTD1例;筛查低风险孕妇中诊断21三体2例,无18三体和ONTD.21三体检出率为9/11、阳性预测值为1.05％ （9/855）; 18三体检出率为1/1、阳性预测值为1.35％（1/74）;ONTD检出率为1/1、阳性预测值为1.92％（1/52）.（3） 16 000例孕妇发生不良妊娠结局239例（不良妊娠结局组）,发生率为1.49％（239/16 000）;孕期产检正常、新生儿出生健康的7 760例孕妇设为健康孕妇组.两组孕妇的预产年龄、体质量和血清学三联筛查指标MoM值分别进行比较,差异均有统计学意义（P＜0.01）.（4）不良妊娠结局组孕妇血清学AFP MoM值＞2.0、F-β-hCG MoM值＞2.0、uE3 MoM值＜0.5的发生率分别为7.95％（19/239）、23.85％（57/239）和4.18％（10/239）;仅有两项指标MoM值异常的发生率为5.02％（12/239）、三联指标MoM值均异常的发生率为0.84％（2/239）;健康孕妇组孕妇三联指标中仅有两项指标MoM值异常的发生率为0.14％（11/7 760）、三联指标MoM值均为异常的发生率为0.两组孕妇血清学三联筛查各指标MoM值异常发生率比较,差异均有统计学意义（P＜0.01）.结论 孕中期孕妇血清学三联筛查指标异常与不良妊娠结局发生有一定的相关性,孕中期血清学三联筛查对21三体、18三体和ONTD的检出有较高的实用价值.

Objective To investigate the predictive value of abnormal multiples of the median （MoM） of second trimester maternal serum triple screening （STMSTS） markers for adverse pregnancy outcomes.Methods 16 000 singleton pregnancies at 15＋0 to 20＋6 weeks＇ gestation who underwent STMSTS between July 2010 and January 2013 in the First Hospital of Jilin University were recruited.Maternal serum AFP,free β-hCG （F-β-hCG） and unconjugated estriol （uE3） levels were measured using time-resolved fluoroimmunoassay,and then convened to MoM.LifeCycle 3.2 software was used to calculate risk,and a risk value greater than 1 in 270 or 1 in 350 was considered as high risk for trisomy 21 syndrome （Down syndrome,DS） and trisomy 18 syndrome （Edwards syndrome,ES）,respectively.MoM of AFP more than 2.5was considered high risk for open neural tube defect （ONTD）.Amniocentesis and karyotyping,ultrasound screening were advised for high risk women.AFP,F-β-hCG higher than 2.0 MoM or uE3 lower than 0.5MoM was considered as abnormal,respectively.The MoM of STMSTS marker between women with adverse pregnancy outcome and with normal outcome was compared.Results （1） The median MoM of AFP,F-β-hCG and uE3 was 0.91 MoM,0.94 MoM and 1.05 MoM,respectively.Of the 16 000 pregnant women,there was no statistical difference in the median MoM of triple screening marker at different weeks of gestation （P〉0.05）.The positive rate of DS,ES and ONTD in women ≤35 years old （n=14 972） was 4.03% （603/14 972）,0.36%（54/14 972） and 0.29%（44/14 972） respectively.And in women〉35 years old（n=1 028）,the positive rate was 24.51% （252/1 028）,1.95% （20/1 028） and 0.78% （8/1 028）,respectively.There was a statistically significant difference of positive rate between the two groups（P〈0.05）.（2） 9 cases of DS,1 case of ES and 1 ease of ONTD were found in the high risk group,and 2 cases of DS in the low risk group.The detection rate of DS,ES and ONTD was 9/11,1/1 and 1/1 respectively; and the positive predictive value was 1.05%（9/855）,1.35%（1/74） and 1.92%（1/52）,respectively.（3）The incidence of adverse outcome （group 1） was 1.49 %（239/16 000）.7 760 pregnant women in this study were healthy during pregnancy,so were their fetuses （group 2）.There were significant differences in the age at delivery,body weight and markers＇ MoM of STMSTS between the two groups（P〈0.01）.（4） In group 1,the rate of abnormal MoM of AFP or F-β-hCG was 7.95%（19/239） and 23.85% （57/239）,and the abnormal rate of MoM of uE3 was 4.18%（10/239）.The rate of two abnormal MoM of markers was 5.02%（12/239）; the rate that all three MoM were abnormal was 0.84%（2/ 239）.However,in group 2,the rate of two abnormal MoM of markers was 0.14 %（11/7 760）; and the rate that all three MoM were abnormal was 0.There was a significant difference of abnormal MoM of maternal serum marker between the two groups （P〈0.01）.Conclusions There is a relationship between abnormal marker of STMSTS and adverse outcomes.STMSTS show a high value in the detection of DS,ES and ONTD.