Methylome analysis of cfDNA to predict preeclampsia presymptomatically

Abstract

Background/Objectives: Belgium was the first country to fully reimburse the noninvasive prenatal screening (NIPS) as a nationwide first-tier screening test to all pregnant women. Different commercial and in-house developed NIPS technologies are being used. Although the accuracies (sensitivity, specificity, positive predictive value, negative predictive value) of the commercial tests are provided by the companies, multicentric longitudinal studies to monitor and compare performance of those methods are lacking. Methods: Since all invasive prenatal genetic testing following positive NIPS are analyzed at the Belgian genetic centers, we are uniquely positioned to determine the performance of different NIPS technologies. From all invasive genetic tests done following a positive NIPS in a clinical laboratory between 01/01/2020 and 01/ 05/2021, the PPVs were compared per technologies. Results: For 303 positive NIPS; 134, 37 and 24 were respectively indicative of trisomy 21, 18 and 13. For trisomy21, the actual PPVs for VeriSeq®(Illumina), Harmony®(Roche) and Vanadis®(Perkin-Elmer) were respectively 69%, 91% and 65%, significantly lower than the 95%, 98% and 94% advertised. The PPV from the 8 genetic centers using a Laboratory Developed Test (LDT) was 92% (1). Conclusion: This difference in PPV has a significant impact on pregnant women and the health care system. In Belgium there are about 120000 pregnancies/year. For example, with a population incidence for trisomy21 of 0.3%, a PPV of 69% versus 92% corresponds to a yearly increase of unnecessary invasive tests from 28 to 112. Our study underscores the value of LDT to improve pre-natal health care.