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

Abstract

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 singlenucleotide 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

Performance of single‐gene noninvasive prenatal testing for autosomal recessive conditions in a general population setting

“…Outcomes were solicited from 3299 individuals and were obtained from 526 individuals for a total of 528 sgNIPT outcomes from 253 clinical practices across 34 US states and Puerto Rico. The outcomes were successfully obtained for 25 affected neonates of the expected 38 affected fetuses in 42,067 pregnant individuals, a collection rate for affected cases that is greater than other prenatal studies of similar design 23–25 . The average GA at the time the sample was collected was 16.4 weeks (median 13.9 weeks; range 10–37 weeks) and the average FF was 7.8% (median 6.4%, range 1.5%–35%).…”

“…The outcomes were successfully obtained for 25 affected neonates of the expected 38 affected fetuses in 42,067 pregnant individuals, a collection rate for affected cases that is greater than other prenatal studies of similar design. [23][24][25] The average GA at the time the sample was collected was 16.4 weeks (median 13.9 weeks; range 10-37 weeks) and the average FF was 7.8% (median 6.4%, range 1.5%-35%). These characteristics were similar in the full eligibility cohort (average GA: 15.7 weeks, average FF: 7.4%).…”

“…The current study examined over 42,000 cases collected from 811 predicted affected cases, a collection rate that compares favorably with other published studies. [23][24][25] The prioritization of outcome collection from cases with high-risk NIPT results allowed for estimation of sensitivity for these conditions with US population frequencies of approximately 1 in 2000 for HBB conditions, 1 in 2500 for CF, 1 in 8000 for SMA and less than 1 in 100,000 for HBA conditions; for an overall frequency of approximately 1 in 1000. [41][42][43][44][45] To account for the uneven collection in high-risk and low-risk cases, the end-to-end clinical sensitivity and specificity were modeled and calculated.…”

Maternal Malignancy After Atypical Findings on Single-Nucleotide Polymorphism–Based Prenatal Cell-Free DNA Screening

“…This approach differs from massively parallel shotgun sequencing methods (DNA fragment counting) in that it can distinguish between maternal and fetal imbalances and detect chromosomal segregation errors that do not have proportional copy number differences between the chromosomes (eg, triploidy, complete mole, and uniparental disomy). 27 , 28 …”

“…This approach differs from massively parallel shotgun sequencing methods (DNA fragment counting) in that it can distinguish between maternal and fetal imbalances and detect chromosomal segregation errors that do not have proportional copy number differences between the chromosomes (eg, triploidy, complete mole, and uniparental disomy). 27,28 Cases were considered suspicious for maternal malignancy if retrospective bioinformatics and visual inspection of the SNP plot were suggestive of multiple maternal copy number variants across at least two of the tested chromosomes (Fig. 1).…”