Two-stage first-trimester screening for trisomy 21 by ultrasound assessment and biochemical testing

This study was carried out to examine the performance of a contingent policy in first-trimester screening for trisomy 21, in which the estimated risk was first derived by a combination of maternal age, fetal nuchal translucency (NT) thickness, presence/absence of the nasal bone, blood flow in the ductus venosus or flow across the tricuspid valve, and biochemical testing was carried out only in those who were found to have an intermediate risk. We also examined the performance of a policy in which the estimated risk was first derived by a combination of maternal age and biochemical testing, and ultrasound examination was carried out only in those with an intermediate risk.

The data for this study were derived from prospective screening for trisomy 21 in singleton pregnancies, using, as markers, a combination of maternal age, fetal NT thickness and maternal-serum free β-human chorionic gonadotropin (β-hCG) and pregnancy-associated plasma protein-A (PAPP-A), in a one-stop clinic for first-trimester assessment of risk at 11 + 0 to 13 + 6 weeks of gestation. Assessment of the fetal nasal bone, ductus venosus flow and tricuspid flow were also routinely performed by appropriately trained sonographers. The performance of different screening policies was examined.

The study population consisted of 19 614 pregnancies with a normal karyotype or delivery of a phenotypically normal baby (euploid group) and 122 cases of trisomy 21. The best performance was achieved by a contingent policy in which first-stage screening was based on maternal age, fetal NT thickness and either tricuspid valve or ductus venosus blood flow, followed by biochemical testing only those with an intermediate risk, of 1 in 51 to 1 in 1000 (which constituted about 20% of the total). The performance of contingent screening in which first-stage testing relies on biochemistry was poorer than when first-stage screening was performed by ultrasound examination because, in order to achieve the same detection rate, the false-positive rate was twice as high.

Effective first-trimester screening for trisomy 21 can be achieved by a contingent policy in which first-stage testing is based on ultrasound examination and second-stage biochemical testing is carried out in only 20% of the patients.