Armelle Duquenne, Nathalie Brison, Ilse Parijs, Angelica Pagliazzi, Machteld Baetens, Bettina Blaumeiser, Marie Bruneau, Saskia Bulk, Bert Callewaert, Sandra Coppens, Michelle Deberg, Anne De Leener, Marjan De Rademaeker, Julie Désir, Koenraad Devriendt, Annelies Fieuw, Jean-Stéphane Gatot, Mauricette Jamar, Sandra Janssens, Lore Lannoo, Axel Marichal, Björn Menten, Colombine Meunier, Bruno Pichon, Sonia Rombout, Ileen Slegers, Yves Sznajer, Olivier Vanakker, Kim Van Berkel, Leen Vancoillie, Ann Van Den Bogaert, Isabelle Vandernoot, Kris Van Den Bogaert, Joris R Vermeesch, Katrien Janssens
This study confirms the reported accuracy of commercial tests and LDT, while showing that LDT generally outperforms commercial tests. Despite high specificities across tests, differences in PPVs significantly impact pregnant people and the national health care system.
OBJECTIVE: Prenatal cell-free DNA screening is widely used to assess the risk of fetal trisomy 21, 18, and 13. Although commercial and laboratory-developed tests (LDTs) show high accuracy in validation studies, real-world longitudinal performance data are lacking.
METHOD: In Belgium, prenatal cell-free DNA screening is a population screening offered to all pregnant people, regardless of their a priori risk. Over 3 years, all confirmatory diagnostic tests after a positive prenatal cell-free DNA screening result were recorded along with the technologies used and their outcomes. Positive predictive values (PPVs) for the three common fetal trisomies were calculated per technology.
RESULTS: A total of 1158 diagnostic tests were performed after a positive prenatal cell-free DNA screening. Of these, 58.5% came from an LDT, 15.7% from VeriSeq (Illumina), 6.6% from Harmony (Roche), 5% from Vanadis (Perkin-Elmer); for 14.2% the technology could not be traced. PPVs ranged from 92.2% to 65.7% for trisomy 21, from 82.8% to 44.4% for trisomy 18, and from 40% to 18.2% for trisomy 13. Overall, the LDT performed better than the commercial tests.
CONCLUSION: This study confirms the reported accuracy of commercial tests and LDT, while showing that LDT generally outperforms commercial tests. Despite high specificities across tests, differences in PPVs significantly impact pregnant people and the national health care system.