Positive predictive value of a single nucleotide polymorphism (SNP)-based NIPT for aneuploidy in twins: Experience from clinical practice.

Objective: Twins account for approximately 1 in 30 live births in the United States. However, there are limited clinical experience studies published in noninvasive prenatal testing (NIPT) for detecting aneuploidies in twins. This study reports the performance of an SNP-based NIPT in the largest cohort with known outcomes for high-risk aneuploidy results.

Method: This is a retrospective analysis of 18,984 results from commercial single-nucleotide polymorphism (SNP)-based NIPT tests performed in twins between October 2, 2017 and December 31, 2019. Follow-up for all 211 high-risk cases was solicited.

Results: Follow-up outcomes were obtained in 105 cases. Positive predictive values (PPVs) for high-risk results were 88.7% (63/71, 95% Confidence Interval [CI]: 79.0%-95.0%) for trisomy 21% and 72.7% (8/11, 95% CI: 39.0%-94.0%) for trisomy 18. The results were stratified into monozygotic (MZ) and dizygotic (DZ). The PPVs in MZ were 100% for both trisomy 21 (4/4, 95% CI: 40%-100%) and trisomy 18 (1/1, 95% CI: 2.5%-100%). No trisomy 13 cases were detected in the MZ group. The PPVs in DZ were 88.1% (59/67, 95% CI: 77.8%-94.7%), 70.0% (7/10, 95% CI: 34.8%-93.3%), and 66.7% (2/3, 95% CI: 9.4%-99.2%) for trisomy 21, trisomy 18, and trisomy 13, respectively.

Conclusion: The performance of SNP-based NIPT in this large twin cohort was comparable to previously reported twin NIPT studies. SNP-based NIPT allows for zygosity-based PPV assessment.