Prenatal screening using maternal serum alpha-fetoprotein, human chorionic gonadotropin, and unconjugated estriol: two-year experience in a health maintenance organization.

The objective of this study was to evaluate a 2-year experience in a health maintenance organization with mid-trimester maternal serum screening with alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG), and unconjugated estriol (UE) as a screen for fetal Down's syndrome. Women at 15-20 weeks gestation were offered triple marker screening. A patient-specific second trimester risk of 1:295 for Down's syndrome was used as a threshold for referral. Women at risk for trisomy 18 were identified by a protocol with fixed low cutoffs. The AFP threshold for referral for neural tube defects (NTD) was 2.0 multiples of the median (MoM). Patients at risk were offered ultrasonography, genetic counseling, and prenatal diagnosis. A total of 6,474 samples were drawn. The initial screen positive rate for Down's syndrome was 7.1%. After ultrasound evaluation, 351 (5.7%) of the remaining 6,197 women were still at risk for Down's syndrome. After genetic counseling, 292 (4.7%) women underwent prenatal diagnosis. Overall, 12 of 16 (75%) cases of Down's syndrome were detected antenatally by triple marker screening. Using AFP alone, only 3 of 14 (21%) cases of Down's syndrome in women under 35 years would have been detected. We detected 1 abnormal karyotype (including one 45, X) for every 22 amniocenteses performed for abnormal Down's syndrome screening. For trisomy 18, 13 women (0.2%) were at risk and, of these, 3 cases were diagnosed. All 6 cases of NTD during the study period were detected by AFP after identifying 3.8% of women as at risk. In conclusion, in the setting of a health maintenance organization where abnormal screening tests were managed by a single referral center, triple marker screening was effective not only for screening for fetal Down's syndrome, but also for trisomy 18 and NTD.