Second trimester two-step trisomy 18 screening using maternal serum markers.

Trisomy 21 maternal serum marker screening has led to screening for other anomalies, including trisomy 18. Trisomy 18 is generally prenatally diagnosed because of major morphological defects. However, in up to 30% of cases ultrasound signs are unclear, and in most cases diagnosis is performed late in pregnancy. Of the different maternal serum markers, PAPP-A is now considered as the best for trisomy 18 screening. However, pregnancy-associated plasma protein A (PAPP-A) is of value in first trimester screening for trisomy 21, but not in the second trimester. We therefore propose a two-step screening strategy. Based on 45 trisomy 18 cases, we confirm the values of alpha-fetoprotein (AFP) (median 0.61 MoM), free beta-human chorionic gonadotrophin (beta-hCG) (median 0.24 MoM) and of PAPP-A (median 0.08 MoM). In the first step, a 0.5 MoM cut-off for AFP or for free beta-hCG resulted in detection of 37/45 trisomy 18 cases (82%) with a 10% false-positive rate. The second step consisted of the measurement of PAPP-A for all these false-positive cases. Using a PAPP-A cut-off of 0.5 MoM, all the 37 trisomy 18 cases were detected, but now with a 0.1-0.2% false-positive rate. Amniocentesis was only offered to these few patients. This two-step second trimester screening will be of value for patients who have not been included in first trimester screening based on nuchal translucency (NT) measurement combined with the first trimester markers, PAPP-A and free beta-hCG.