Non-invasive prenatal testing (NIPT) by analysis of cell-free fetal DNA has revolutionised prenatal screening and is a highly accurate test for trisomy 21 (Down syndrome). Since its implementation in 2011, the test has become more accessible and increasingly used as a first- or second-tier screening modality.
New technologies using genome-wide cell-free DNA analysis have also been incorporated into expanded panels without proper clinical validation. The true performance of the test in screening for these rare conditions remains unknown. Many such conditions are rare in the fetus and have variable phenotype, and high-risk results from NIPT for rare chromosomal imbalances are often false-positive results due to placental confined mosaicism, leading to increasing need for invasive tests and generating unnecessary anxiety in parents. A recent warning from the Food and Drug Administration in the United States advocated for caution in the use and interpretation of cell-free DNA results for rare chromosomal conditions.
In this lecture, A/Prof Daniel Rolnik will discuss technical aspects of cell-free DNA technology, the importance of performing and ultrasound before testing, its accuracy for the common trisomies, and new data on the accuracy of the test for rarer conditions, such as sex chromosome abnormalities, rare autosomal trisomies, segmental imbalances (deletions and duplications), and microdeletion syndromes.