Genome-Wide Non-Invasive Prenatal Testing (GW-NIPT) can provide positive results not
only for common autosomal aneuploidies but also for rare autosomal trisomies (RATs)
and structural chromosomal abnormalities (StrCAs). Due to their rarity, there is currently
insufficient information on positive predictive value PPV of RAT and StrCA-positive
cases in the literature. In this study, the screening accuracy and pregnancy outcomes
of cases positive for rare chromosomal abnormalities were examined based on publications
in which GW-NIPT testing was performed. True positive cases were determined using
two different methodologies. One was a confirmed methodology, where only cases validated
by genetic testing were considered true positives with a definite diagnosis, and the
other was an extended methodology, where, in addition to cases confirmed by genetic
testing, intrauterine fetal death and termination of pregnancy due to an abnormality
confirmed by ultrasound examination were also considered true positives, where no
diagnosis had been made but the fetus was probably affected. Seventeen studies were
analyzed, with a total GW-NIPT population of 740,076. Of these, 1,738 were RAT positive.
Using the confirmed method, we found the highest rates of true positives in T16, followed
by T22, and T2, using the extended method, the highest rate of true positives in T15,
T16 and T22. This is the first meta-analysis to determine the frequency of rare chromosomal
abnormalities, test-positive rates, and the PPV of each chromosomal abnormality with
high precision. Our results could aid pre- and post-test genetic counselling and help
patients and clinicians in their decision-making.
