First-trimester screening: lessons from clinical trials and implementation.

摘要

Amniocentesis has traditionally been offered to the higher-risk gravidas of 35 years of age or older, whorepresent only about 5% of pregnant women but givebirth to 25-30% of infants with trisomy 21 . In the 1980s, studies showed that, compared to chromosomally normal fetuses, pregnant women with a fetus with Down's syndrome had median maternal serum levels that were lower for alpha-fetoprotein (AFP) and unconjugatedestriol (uE_3),and higher for human chorionicgonadotropin (hCG) [3-5]. When measured in concert between 15 and 20 weeks of gestation, these feto-placentalmarkers can detect 55-75% of Down's syndrome [6-9]. This triple marker test is widely used to screen fortrisony 21, trisomy 18 (decreased hCG, uE_3, AFP) and neural tube defects (elevated AFP). The addition of afourth marker, inhibin-A,further increases the sensitivityfor trisomy 21 , as shown in Table 1. Thus, maternal serum markers, measured in multiple of median(MOM), have been used to determine likelihood ratios for adjusting the risk based on maternal age. Fetal sonography targeting the phenotype of trisomy 21 has been a logical-up evaluation to further define the risk. Disadvantages of maternal serum screening include lack of sensitivity and specificity for Down's syndrome and a comparatively late, second-trimester diagosis of a chromosome disorder.