Counseling prior to cfDNA screening: are we giving the right numbers?

In this modeled study, we aim to evaluate the test performance of cfDNA screening for trisomy 21, 18, and 13 individually and in combination to help with pre-test counseling.

We used the German birth statistics 2023 and calculated the expected number of trisomy 21, 18, and 13 for each maternal age. The number of screen-positive tests (true and false) for trisomy 21, 18, and 13 was estimated based on maternal and gestational age-related risks for the three trisomies. The positive predictive value was calculated for each trisomy individually and in combination according to maternal age. In addition, we applied an uninformative test rate of 1.2%.

In 2023, 692,730 children were born in Germany and the predicted number of trisomy 21, 18, and 13 fetuses are 2,521.71, 1,084.70, and 344.31, respectively. In total, cfDNA screening in all pregnancies would result in 4,940.9 screen-positive pregnancies (screen-positive rate of 0.7%) and 13,253.69 uninformative tests. Up to 34 years of age, the screen-positive rate would be between 0.3 and 0.5%, but for older women, the screen-positive rate would be between 0.9 and 11.3%. The combined PPV for the three trisomies would be 48.7% in women of less than 20 years of age and increases to 98.8% in women who are 45 years old or older.

cfDNA screening is an excellent screening test for the most common trisomies. However, counseling prior to the screening test is essential. Our study provides useful numbers which can be used for this purpose.