Screening Performance and Costs of Different Strategies in Prenatal Screening for Trisomy 21

Objective: Cell-free fetal DNA (cffDNA) testing has opened new options in prenatal screening for trisomy 21. Due to the higher costs of cffDNA testing there is an ongoing debate on how to combine different screening strategies.

Methods: For this study, a model-based approach was used to evaluate all births in Germany in 2012 together with the percentage of euploid and trisomic pregnancies. Detection rates (DR), false positive rates (FPR), the costs of different screening strategies for trisomy 21 and combinations of these strategies were compared. The number of fetuses with trisomy 21 at 12 + 0 weeks of gestation was estimated based on maternal age distribution. We examined the screening per- formance of a screening strategy based on mater- nal age, first trimester screening (FTS) and cffDNA testing as well as the combinations „maternal age and cffDNA” and „FTS and cffDNA”.

Results: In 2012 673 544 children were born. Median maternal age at delivery was 30.2 years (25th-75th quartile: 27.0 – 34.0). Based on maternal age distribution the expected number of fetuses with trisomy 21 at 12 weeks' gestation was 1788. Our study population therefore consisted of 675 332 pregnancies. Screening based only on maternal age or FTS or cffDNA resulted in detec- tion rates of 63.3%, 92.2% and 99.0% and false positive rates of 21.8%, 8.0% and 0.1%, respectively. When maternal age was combined with cffDNA, cffDNA testing was only offered to women over a certain age; if a cut-off of 30 years was used, this resulted in a DR of 85.2% and a FPR of 1.7%. If primary screening consisted of FTS with cffDNA testing only done when the risk was be- tween 1: 10 and 1: 1000, the detection rate was 96.7% and the false positive rate was 1.2%.

Conclusion: In this model-based study we showed that prenatal screening for trisomy 21 can be improved even more by combining FTS.