BACKGROUND: Reliable individual risk calculation for trisomy (T) 13, 18, and 21 in first-trimester screening depends on good estimates of the medians for fetal nuchal translucency thickness (NT), free β-subunit of human chorionic gonadotropin (hCGβ), and pregnancy-associated plasma protein-A (PAPP-A) in maternal plasma from unaffected pregnancies. Means and SDs of these parameters in unaffected and affected pregnancies are used in the risk calculation program. Unfortunately, our commercial program for risk calculation (Astraia) did not allow use of local medians. We developed 2 alternative risk calculation programs to assess whether the screening efficacies for T13, T18, and T21 could be improved by using our locally estimated medians. METHODS: We established these estimates from 19 594 women with singleton pregnancies and from 100 pregnant women carrying a fetus affected with trisomy (11 with T13, 23 with T18, and 66 with T21). All measured values were recalculated to a multiple of the median (MoM) and log(10) transformed; the mean and SD were calculated for each group. RESULTS: At a given risk cutoff value, we observed a slight improvement in detection rate (DR) for T13, T18, and T21 for a slightly higher false-positive rate (FPR) compared with the commercial program. The lower FPR in the commercial program was caused mainly by an inaccuracy in the PAPP-A median. CONCLUSIONS: Center-specific medians for NT, hCGβ, and PAPP-A should be used in risk calculation programs to ensure high DRs and low FPRs for all 3 trisomies at a given risk cutoff.
BACKGROUND: Reliable individual risk calculation for trisomy (T) 13, 18, and 21 in first-trimester screening depends on good estimates of the medians for fetal nuchal translucency thickness (NT), free β-subunit of human chorionic gonadotropin (hCGβ), and pregnancy-associated plasma protein-A (PAPP-A) in maternal plasma from unaffected pregnancies. Means and SDs of these parameters in unaffected and affected pregnancies are used in the risk calculation program. Unfortunately, our commercial program for risk calculation (Astraia) did not allow use of local medians. We developed 2 alternative risk calculation programs to assess whether the screening efficacies for T13, T18, and T21 could be improved by using our locally estimated medians. METHODS: We established these estimates from 19 594 women with singleton pregnancies and from 100 pregnant women carrying a fetus affected with trisomy (11 with T13, 23 with T18, and 66 with T21). All measured values were recalculated to a multiple of the median (MoM) and log(10) transformed; the mean and SD were calculated for each group. RESULTS: At a given risk cutoff value, we observed a slight improvement in detection rate (DR) for T13, T18, and T21 for a slightly higher false-positive rate (FPR) compared with the commercial program. The lower FPR in the commercial program was caused mainly by an inaccuracy in the PAPP-A median. CONCLUSIONS: Center-specific medians for NT, hCGβ, and PAPP-A should be used in risk calculation programs to ensure high DRs and low FPRs for all 3 trisomies at a given risk cutoff.
Authors: S Kate Alldred; Yemisi Takwoingi; Boliang Guo; Mary Pennant; Jonathan J Deeks; James P Neilson; Zarko Alfirevic Journal: Cochrane Database Syst Rev Date: 2017-03-15