The potential of expanded noninvasive prenatal screening for detection of microdeletion and microduplication syndromes

Objectives To evaluate the clinical potential of a higher resolution noninvasive prenatal screening (NIPS-Plus) test for detection of microdeletion/microduplication syndromes (MMS) in addition to common aneuploidies. Methods In a multicenter prospective study, 37,002 pregnant women with unremarkable first-trimester ultrasound scans had a NIPS-Plus test. Ultrasound screen positive women were not included in this study. Results Of 36,970 ultrasound negative women there were 291 NIPS-Plus screen positive results indicating 237 aneuploidies and 54 MMS. Following amniocentesis, 171 (72%) were confirmed as genuine, comprising 3 T13s, 10 T18s, 61 T21s, 70 SCAs and 27 MMS. The PPV for MMS with unremarkable ultrasound findings was 50%. Routine clinical examination of children born from NIPS-Plus negative pregnancies revealed no obvious signs of chromosome disease syndromes at one year of age. Conclusions NIPS-Plus has the potential for clinical utility not only for routine aneuploid screening but also for MMS that do not show overt signs during early pregnancy ultrasound screening. We suggest that ultrasound with NIPS-Plus in combination with appropriate counselling could be considered as a comprehensive first-tier prenatal screening approach for all pregnant women.