Noninvasive prenatal testing for assessing foetal sex chromosome aneuploidy: a retrospective study of 45,773 cases

Abstract

Objective To assess the positive predictive value (PPV) of noninvasive prenatal testing (NIPT) as a screening test for sex chromosome aneuploidy (SCA) with different maternal characteristics and prenatal decisions in positive cases. Materials and methods We retrospectively analysed 45,773 singleton pregnancies with different characteristics that were subjected to NIPT in the Maternity and Child Health Hospital of Anhui Province. The results were validated by karyotyping. Clinical data, diagnostic results, and data on pregnancy outcomes were collected. Results In total, 314 cases were SCA positive by NIPT; among those, 143 underwent invasive prenatal diagnostic testing, and 58 were true-positive. Overall, the PPVs for 45,X, 47,XXX, 47,XXY and 47,XYY were 12.5%, 51.72%, 66.67% and 83.33%, respectively. Interestingly, when only pregnant women of advanced maternal age (AMA) were screened, the PPVs for 45,X, 47,XXX, 47,XXY and 47,XYY were 23.81%, 53.33%, 78.95%, and 66.67%, respectively. The frequency of SCA was significantly higher in the AMA group than in the non-AMA group. The frequencies of 47,XXX and 47,XXY were significantly correlated with maternal age. Conclusion NIPT performed better in predicting sex chromosome trisomies than monosomy X, and patients with 45,X positive foetuses were more eager to terminate pregnancy than those with 47,XXX and 47,XYY. AMA may be a risk factor of having a foetus with SCA. Our findings may assist in genetic counselling of AMA pregnant women. Our pre- and posttest counselling are essential for familiarizing pregnant women with the benefits and limitations of NIPT, which may ease their anxiety and enable them to make informed choices for further diagnosis and pregnancy decisions.

Non-Invasive Prenatal Testing (NIPT) Results for Participants of the eXtraordinarY Babies Study: Screening, Counseling, Diagnosis, and Discordance

“…A unique aspect of prenatal genetic counseling following an NIPT result positive for SCA is the presentation, interpretation and often calculation of the positive predictive value (PPV). The PPV for NIPT results regarding SCAs is inherently variable among laboratories with published values ranging from 20-86% (Lu et al, 2021; Petersen et al, 2017; Ramdaney et al, 2018; Shi et al, 2021). A 2019 review of 10 NIPT laboratory reporting methods concluded recommendations that laboratory reports visibly and clearly state the detection rate (DR), specificity (SPEC), positive predictive value (PPV), and negative predictive value (NPV) for all conditions being screened in order to assist patients and providers in making decisions and interpreting results (Skotko et al, 2019).…”

“…Prenatal genetic counseling for SCA-positive NIPT results is challenged by relatively poor positive predictive values for SCAs in NIPT, highly variable phenotypic outcomes, and historic peer-reviewed publications inherently biased by ascertainment (Mennuti, Chandrasekaran, Khalek, & Dugoff, 2015; Petersen et al, 2017; Wang et al, 2020). While NIPT has been demonstrated to have high sensitivity and specificity in identification of other chromosomal conditions, such as Trisomy 21/Down syndrome, the positive predictive values (PPV) for the detection of SCAs have varied from 25-89% and many companies fail to include these test statistics for SCAs on their result reports entirely (Lu et al, 2021; Shi et al, 2021; Skotko et al, 2019; Zheng et al, 2020). Phenotypes among SCAs range widely from mild dysmorphisms and tall stature to increased rates of cognitive impairment, medical conditions and psychological features.…”

Prenatal Testing – What Is It Good For? A Review and Critique

“…A Welsh survey of pregnancies with Turner syndrome found a termination rate of 66% over 10 years. A Chinese study of sex chromosome aneuploidies detected through NIPT screening reported termination rates of 85%, 73%, 20%, and 10% for Turner syndrome, Klinefelter syndrome, XXX, and XYY, respectively [46]. In a study from Hong Kong, the overall termination rate for sex chromsome aneuploidies was 55.6%, with specific rates of 91.7%, 48.0%, 23.4%, and 4.8%, for 45,X, 47,XXY, 47,XXX, 47,XYY, respectively [47].…”

Genetic Counseling and Management: The First Study to Report NIPT Findings in a Romanian Population

“…Sex chromosome aneuploidies that can also be identified using NIPT have a lower detection rate, especially monosomy X, with a higher false positive rate compared to autosomal trisomies. The average positive predictive value (PPV) for sex chromosome anomalies screening was estimated at 40.56% [5,11]. NIPT has several limitations regarding the detection of more rare fetal chromosomal abnormalities, other than aneuploidy for 3 (13,18,21) or 6 pairs (13,18,21,9,16,22) of autosomal chromosomes, or the identification of cases with mosaicism.…”