The predictive value of noninvasive prenatal screening for copy number variations: a cohort study and a systematic meta-analysis

ABSTRACTABSTRACTObjective To assess the diagnostic accuracy of noninvasive prenatal screening (NIPS) in screening for copy number variations (CNVs).Methods We conducted a systematic review and meta-analysis by combining our study results with those reported in other articles. We retrospectively collected the data of pregnant women with NIPS testing in the Hangzhou Women's Hospital from December 2019 to February 2022. Simultaneously, a systematic search of PubMed, EMBASE, and Web of Science was carried out to identify all relevant peer-reviewed publications. Statistical analysis was performed based on the random-effects model to determine a pooled estimate of the positive predictive value (PPV).Results A total of 29 studies involving 2,667 women were included for analysis. The pooled PPV of NIPS in the detection of CNVs was 32.86% (95% confidence interval [24.61–41.64]). Statistical heterogeneity was high, while no significant publication bias was found in this meta-analysis. There were insufficient data to accurately determine sensitivity and specificity, as most studies only performed confirmatory tests on high-risk women.Conclusions The PPV of NIPS in screening for CNVs was approximately 33%. Cautions should be kept in mind for the pretest guidance and subsequent after-test counseling when offering such genome-wide NIPS tests.KEYWORDS: Diagnostic accuracynoninvasive prenatal screeningcopy number variationdeletion/duplicationpositive predictive value Article highlights This meta-analysis included a total of 29 studies involving 2,667 pregnant womenThe pooled positive predictive value of NIPS in the detection of CNVs was 32.86%PPV was higher in the high-risk group (34.42%) than the low-risk group (27.04%)Insufficient data limit the capacity to compute the pooled sensitivity/specificityDeclaration of interestThe authors have no other relevant affiliations of financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.Reviewers DisclosurePeer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.Supplementary materialSupplemental data for this article can be accessed online at https://doi.org/10.1080/14737159.2023.2233415.Additional informationFundingThis work was financially supported by grants from the Natural Science Foundation of Zhejiang Province (Grant No. LBY21H040001), the National Natural Science Foundation of China (Grant No. 82173530), and the "Pioneer" and "Leading Goose" R&D Program of Zhejiang (2022C03102).