Haddow J E, Palomaki G E, Knight G J, Foster D L, Neveux L M
Foundation for Blood Research, Scarborough, ME 04074, USA.
J Med Screen. 1998;5(3):115-9. doi: 10.1136/jms.5.3.115.
To determine the second trimester Down's syndrome screening performance of maternal serum dimeric inhibin A, both alone and in combination with existing serum markers.
A case-control set of serum samples from patients with Down's syndrome (52) and subjects with matched unaffected pregnancies obtained in a previous cohort study before second trimester amniocentesis and karyotyping. The amniocenteses were performed for reasons other than a positive serum screening test result.
For each serum from a Down's syndrome pregnancy, five serum samples from pregnancies with a normal karyotype were matched for recruitment centre, gestational age, maternal age, and date of amniocentesis. A specific form of inhibin (dimeric inhibin A) was measured using monoclonal antibodies. Measurements of alpha fetoprotein, unconjugated oestriol, and human chorionic gonadotrophin and its free beta subunit were already available. Screening performance was modelled using distribution variables of the analytes coupled with the 1993 age distribution of pregnant women in the United States.
The median dimeric inhibin A level was 2.10 times higher in Down's syndrome pregnancies. When dimeric inhibin A was combined with maternal age and three other serum markers (alpha fetoprotein, unconjugated oestriol, and human chorionic gonadotrophin) the Down's syndrome detection rate increased to 75% (from 66%) at a 5% false positive rate. If dimeric inhibin A could be added for less than $31 (ranging from $16 to $39 depending on the detection rate, markers chosen, and method of dating), the cost of detecting each Down's syndrome pregnancy and the number of procedure related fetal losses would both be reduced.
The addition of dimeric inhibin A to prenatal screening programmes for Down's syndrome should be considered, or possibly it could be substituted for an existing serum marker. One barrier to implementation in the United States, however, is the unavailability of kits with Food and Drug Administration approval.
确定孕中期孕妇血清二聚抑制素A单独及与现有血清标志物联合检测唐氏综合征的筛查效能。
一组病例对照血清样本，来自唐氏综合征患者（52例）以及在前瞻性队列研究中获得的、与未受影响妊娠匹配的对象，这些样本采集于孕中期羊膜腔穿刺术和染色体核型分析之前。进行羊膜腔穿刺术的原因并非血清筛查试验结果呈阳性。
对于每一份唐氏综合征妊娠的血清样本，选取五份来自核型正常妊娠的血清样本，根据招募中心、孕周、孕妇年龄和羊膜腔穿刺术日期进行匹配。使用单克隆抗体检测一种特定形式的抑制素（二聚抑制素A）。甲胎蛋白、未结合雌三醇、人绒毛膜促性腺激素及其游离β亚基的检测数据已经具备。利用分析物的分布变量以及1993年美国孕妇年龄分布对筛查效能进行建模。
唐氏综合征妊娠中，二聚抑制素A的中位数水平高出2.10倍。当二聚抑制素A与孕妇年龄及其他三种血清标志物（甲胎蛋白、未结合雌三醇和人绒毛膜促性腺激素）联合使用时，在5%假阳性率的情况下，唐氏综合征的检出率从66%提高到了75%。如果添加二聚抑制素A的成本低于31美元（根据检出率、所选标志物和孕周确定方法不同，成本在16美元至39美元之间），那么检测每例唐氏综合征妊娠的成本以及与操作相关的胎儿丢失数量都将降低。
应考虑在唐氏综合征产前筛查项目中添加二聚抑制素A，或者它也可能替代现有的一种血清标志物。然而，在美国实施该方法的一个障碍是缺乏获得美国食品药品监督管理局批准的试剂盒。
