Multicenter study of first‐trimester screening for trisomy 21 in 75 821 pregnancies: results and estimation of the potential impact of individual risk‐orientated two‐stage first‐trimester screening

Abstract

Objectives: To evaluate the performance of first‐trimester screening for trisomy 21 by a combination of maternal age, fetal nuchal translucency (NT) and maternal serum free β‐human chorionic gonadotropin (β‐hCG) and pregnancy‐associated plasma protein‐A (PAPP‐A). In addition, the potential impact of a new individual risk‐orientated two‐stage approach to first‐trimester screening was examined. Methods: First‐trimester combined screening for trisomy 21 was carried out in 75 821 singleton pregnancies with live fetuses at 11 + 0 to 13 + 6 gestational weeks. The detection and false‐positive rates for different risk cut‐offs were calculated. To examine the potential impact of an individual risk‐orientated two‐stage approach to first‐trimester screening it was assumed that, after first‐trimester combined screening, chorionic villus sampling (CVS) would be performed in all patients with a risk estimate of 1 in 100 or more and in none of those with a risk estimate of less than 1 in 1000. Those in the intermediate‐risk category, with a risk estimate of between 1 in 101 and 1 in 1000, would have further assessment of risk by first‐trimester ultrasound examination to determine presence/absence of the nasal bone, presence/absence of tricuspid regurgitation or normal/abnormal Doppler velocity waveform in the ductus venosus, and CVS would be performed if their adjusted risk became 1 in 100 or more. Results: Fetal NT and maternal serum free β‐hCG and PAPP‐A were successfully measured in all cases. The median maternal age was 31 (range, 13–49) years, the median gestation at screening was 12 (range, 11 + 0 to 13 + 6) weeks and the median fetal crown–rump length was 62 (range, 45–84) mm. Chromosomal abnormalities were identified in 544 pregnancies, including 325 cases of trisomy 21. The estimated risk for trisomy 21 was 1 in 300 or greater in 5.2% of normal pregnancies, in 92.6% of those with trisomy 21, in 88.5% of those with trisomy 18 or 13 and in 85.6% of those with other chromosomal defects. The detection rates for trisomy 21 were about 75% and 80% for respective false‐positive rates of 1% and 2%. In the proposed individual risk‐orientated two‐stage screening for a risk cut‐off of 1 in 100 the total false‐positive rate would vary with the method used for the second stage of screening from 2.1% for absence of the nasal bone to 2.7% for increased impedance in the ductus venosus and 2.7% for tricuspid regurgitation and the respective detection rates would be 92.0%, 94.2% and 91.7%. Conclusions: First‐trimester combined screening for trisomy 21 is associated with a detection rate of about 90% for a false‐positive rate of 5%. Individual risk‐orientated two‐stage screening for trisomy 21 can potentially identify, in the first trimester of pregnancy, more than 90% of affected fetuses for a false‐positive rate of 2–3%. Copyright © 2005 ISUOG. Published by John Wiley & Sons, Ltd.