Screening for Sex Chromosome Aneuploidy by Cell-Free DNA Testing: Patient Choice and Performance

Abstract

Objective: To study patient choice regarding testing for sex chromosome aneuploidy (SCA) and the performance of cell-free DNA (cfDNA) screening for SCA. Methods: Patient choice regarding screening for SCA and factors influencing this choice were evaluated in a single center. In a subsequent two-center study, cases that screened positive for SCA were analyzed to determine the positive predictive value (PPV) for each SCA. Results: In all, 1,957 (61.9%) of the 3,162 patients undergoing cfDNA testing opted for SCA screening. Regression analysis demonstrated that independent predictors of a patient's decision for SCA were earlier gestational age, spontaneous conception, and cfDNA chosen as a primary method of screening. A total of 161 cases screened positive for SCA and follow-up data were available for 118 (73.3%). Forty-six of the 61 cases of 45,X were false-positive results and 15 were concordant with the fetal karyotype (PPV = 24.6%). Seventeen of the 22 cases of 47,XXX were false positive and 5 concordant (PPV = 22.7%). Eleven of the 30 cases of 47,XXY were false positive and 19 concordant (PPV = 63.3%). All 5 cases of 47,XYY were correctly identified, thus yielding a PPV of 100%. Conclusion: More than half of the patients undergoing cfDNA aneuploidy screening also opted for SCA testing, but they were less likely to do so in the presence of an increased risk of trisomy. SCAs involving the X chromosome had a lower PPV than those involving the Y chromosome.

Clinical experience with sex chromosome aneuploidies detected by noninvasive prenatal testing (NIPT): Accuracy and patient decision‐making

“…Previous validation studies were laboratory‐funded and lacked complete clinical follow‐up and insight into patient decision‐making regarding follow‐up diagnostic testing. A few recent studies examining positive NIPT results for SCAs in the clinical setting had relatively small sample sizes (≤50) and/or had limited information on ultrasound findings and patient demographics . These studies have also largely included patients managed through a single hospital system, and thus may not be generalizable.…”

“…While previous studies have indicated that the majority of patients with a positive NIPT for a SCA elect prenatal diagnosis, our clinical experiences highlight that this may not be true for all patient populations. In our study, 88 of the 134 viable pregnancies (65.7%) declined prenatal diagnosis.…”

“…As the majority of women opt to include screening for SCAs on NIPT, our clinical experience reinforces the importance of confirmatory testing and provides evidence that the majority of women decline prenatal diagnosis for a suspected SCA, even in the presence of abnormal ultrasound findings. This information is important for clinicians providing pretest and posttest counseling as the recommendation for postnatal testing should be emphasized.…”

“…A few recent studies examining positive NIPT results for SCAs in the clinical setting had relatively small sample sizes 1,16 (≤50) and/or had limited information on ultrasound findings and patient demographics. 17 These studies have also largely included patients managed through a single hospital system, and thus may not be generalizable. The objective of this study was to present data from a large, multisite university academic center on clinical experiences of positive NIPT results for SCAs, including uptake rates for prenatal diagnosis and patient decision-making.…”

Cell-Free DNA Analysis in Maternal Blood: Differences in Estimates between Laboratories with Different Methodologies Using a Propensity Score Approach

“…Such high-performance screening has been reported for both high-risk pregnancies and in the general population [4][5][6][7][8][9]. Beyond the major trisomies (21,18, and 13), cfDNA testing panels can be expanded to include sex chromosomal aneuploidies and microdeletion syndromes, but this would increase the cumulative FPR [10]. This is due to the low prevalence of some of these conditions -and, consequently, positive predictive values of less than 10% when tested [11].…”