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. Key points What is already known about this topic? Limited clinical experience has been published in noninvasive prenatal testing (NIPT) for detecting aneuploidies in twin pregnancies, despite twins accounting for about 1 in 30 live births in the United States. SNP‐based NIPT provides both zygosity and the individual fetal fractions in dizygotics during prenatal aneuploidy screening in twin pregnancies. What does this study add? This study based on a large cohort of twin pregnancies reports positive predictive values (PPVs) for detecting common aneuploidies in pregnancies identified as high‐risk‐using SNP‐based NIPT. This is the first study to evaluate the PPV in DZ and MZ twins using NIPT.