PhD Scientific Days 2024

Molecular Medicine I.

Genome-Wide, Non-Invasive Prenatal Testing for Rare Chromosomal Abnormalities: A Systematic Review and Meta-Analysis of Diagnostic Test Accuracy

Text of the abstract

Genome-Wide Non-Invasive Prenatal Testing (GW-NIPT) can provide positive results not only for common autosomal trisomies, but also for rare autosomal trisomies (RAT) and structural chromosomal abnormalities (SCA). Due to their rarity, there is currently insufficient information on the positive predictive values (PPV) of RAT and SCA-positive cases in the literature.
To identify more precise risk values to achieve better genetic consultation and clinical decisions.
We investigated the screening performance of positive cases for rare chromosomal aberrations by publications where a GW-NIPT study was performed. True positive cases were determined using two different methodologies. One was a confirmed methodology where only cases confirmed by genetic testing were considered true positives, 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.

A total of 14 studies were analyzed, with a total GW-NIPT population of 582,996. Of these, 1,364 were RAT positive. The pooled proportion of RAT-positive cases was 0.003 (95% CI: [0.002, 0.004]). The pooled PPV with the confirmed method was 0.06 (95% CI: [0.04, 0.10] PI: [0.01, 0.26]), whereas with the extended method, the pooled PPV was 0.12 (95% CI: [0.07, 0.22] PI: [0.01, 0.60]), but PPV varied by chromosome. Using a confirmed method, we found the highest rates of true positives in T16, with a random-effects pooled proportion of 0.00002 among all NIPT, followed by T22, with a random-effects pooled proportion of 0.00002, and T2, with a random-effects pooled proportion of 0.00001. Using an extended method, we found the highest rate of true positives in T22, with a random-effects pooled proportion of 0.00004, followed by T16, with a random-effects pooled proportion of 0.00004, and T15, with a random-effects pooled proportion of 0.00003.

The test-positive and pooled PPV data reported in this publication can help patients select the appropriate NIPT test, whereas PPV values for individual chromosomes and structural chromosomal abnormalities are of significant importance in post-test genetic counseling, choice of confirmation method and patient decision-making.