Huderer-Duric K, Skrablin S, Kuvacic I, Sonicki Z, Rubala D, Suchanek E
Department of Obstetrics and Gynecology, Zagreb University School of Medicine, Croatia.
Eur J Obstet Gynecol Reprod Biol. 2000 Jan;88(1):49-55. doi: 10.1016/s0301-2115(99)00121-9.
to review the contribution of unconjugated estriol in Down's syndrome detection, and influence of maternal age, cut-off choice, and population specificity on the balance between triple-marker test sensitivity and specificity.
Prenatal karyotyping was performed in 2833 pregnant women, 73% of them over the age of 34. Duration of gestation was determined by ultrasound in 98% of women. Prior to amniocentesis, the serum levels of alpha-fetoprotein, human chorionic gonadotropin and unconjugated estriol were evaluated and corrected for weight. The risk of trisomy 21 was calculated for the first 986 subjects using default medians, and for 1847 by our population-specific medians. The cut-off was initially 1:300 at term, but the 1:100 and 1:200 risks were also tested. Down syndrome risk was calculated with alpha-fetoprotein and human chorionic gonadotropin combination as well. Linear logistic regression model was performed to test the ability of aneuploidy markers to classify patients into normal and trisomic groups.
There were twelve cases of Down's syndrome, seven of trisomy 18, four of trisomy 13, and one trisomy 22. Four cases of aneuploidy (16.7%) referred to women younger than 35. With the cut-off risk of 1:300, detection rate was 87.5% and specificity 63.3%, and with 1:100, 66.7% and 79.5%, respectively. The sensitivity for Down's syndrome was from 75% for cut-off=1:100 to 92% for cut-off=1:300, while detection of other trisomies was less successful (58% and 83%, respectively). Exclusion of unconjugated estriol MoM from the risk calculations reduced detection rate by 33% and improved specificity by 4% independently of cut-off choice. Linear logistic regression analysis showed that only unconjugated estriol was able to correctly classify patients between normal and trisomy 21 (p=0.011, odds ratio=1.445), and normal and trisomy 18 (p=0.0023, odds ratio=1.96) groups.
The unconjugated estriol significantly contributes in Down's syndrome detection with cost of slightly reduced specificity. The 1:300 risk caused an unfavorable compromise between sensitivity and specificity. A higher cut-off, 1:100, would indicate performance of amniocentesis in women aged 39 years and older, and in those aged 35-39 only after the screen-positive result.
回顾未结合雌三醇在唐氏综合征检测中的作用，以及孕妇年龄、截断值选择和人群特异性对三联筛查试验敏感性和特异性平衡的影响。
对2833名孕妇进行产前核型分析，其中73%年龄超过34岁。98%的孕妇通过超声确定孕周。在羊膜穿刺术前，评估血清甲胎蛋白、人绒毛膜促性腺激素和未结合雌三醇水平，并根据体重进行校正。对前986名受试者使用默认中位数计算21-三体风险，对1847名受试者使用特定人群中位数计算。最初的截断值为足月时1:300，但也测试了1:100和1:200的风险。还计算了甲胎蛋白和人绒毛膜促性腺激素联合检测的唐氏综合征风险。采用线性逻辑回归模型测试非整倍体标志物将患者分为正常组和三体组的能力。
有12例唐氏综合征、7例18-三体、4例13-三体和1例22-三体。4例非整倍体（16.7%）发生在35岁以下的女性中。截断风险为1:300时，检测率为87.5%，特异性为63.3%；截断风险为1:100时，检测率和特异性分别为66.7%和79.5%。唐氏综合征的敏感性从截断值为1:100时的75%到截断值为1:300时的92%，而其他三体的检测效果较差（分别为58%和83%）。在风险计算中排除未结合雌三醇的倍数中位数，无论截断值如何选择，检测率均降低33%，特异性提高4%。线性逻辑回归分析表明，只有未结合雌三醇能够正确区分正常组和21-三体组（p=0.011，优势比=1.445）以及正常组和18-三体组（p=0.0023，优势比=1.96）。
未结合雌三醇对唐氏综合征检测有显著贡献，但特异性略有降低。1:300的风险在敏感性和特异性之间造成了不利的折衷。较高的截断值1:100表明，对于39岁及以上的女性以及35-39岁且筛查结果为阳性的女性，应进行羊膜穿刺术。
