The epidemic of abnormal copy number variant cases missed because of reliance upon noninvasive prenatal screening

• Published in: Prenatal diagnosis 2018-09, Vol.38 (10), p.730-734
• Main Authors: Evans, Mark I., Andriole, Stephanie, Curtis, Jenifer, Evans, Shara M., Kessler, Alan A., Rubenstein, Andrew F.
• Format: Article
• Language: English
• Subjects: Abnormalities; Comparative Genomic Hybridization - statistics & numerical data; Complications; Copy number; Diagnostic systems; DNA Copy Number Variations; Down syndrome; Down's syndrome; Epidemics; Female; Health care; Humans; Hybridization; Medical screening; Pregnancy; Pregnancy complications; Prenatal diagnosis; Prenatal Diagnosis - statistics & numerical data; Public health; Utilization
• ISSN: 0197-3851; 1097-0223
• DOI: 10.1002/pd.5275

Objective To assess the implications of increasing utilization of noninvasive prenatal screening (NIPS), which may reach 50% with the concomitant decrease in diagnostic procedures (DPs) for its impact on detection of chromosomal abnormalities. Methods We studied our program's statistics over 5 years for DPs and utilization of array comparative genomic hybridization (aCGH). We then modeled the implications in our program if DP had not fallen and nationally of a 50% DP and aCGH testing rate using well‐vetted expectations for the diagnosis of abnormal copy number variants (CNVs). Results Our DP fell 40% from 2013‐2017. Utilization of aCGH for DP nearly tripled. We detected 28 abnormal CNVs. If DP had not fallen, we likely would have detected 60. With 4 million US births per year, 2 million DPs would detect 30 000 abnormal CNVs and 4000 standard aneuploidies. At a 1/500 complication—pregnancy loss rate, the detection/complication ratio is 8.5/1. Conclusions Noninvasive prenatal screening has significantly changed the practice of prenatal screening. However, while increasing the detection of Down syndrome, the concomitant decrease in DP and lack of aCGH results in missing many more abnormalities than the increase in Down syndrome and complications of DP combined. From a public health perspective, such represents a missed opportunity for overall health care delivery. What's already known about this topic? Noninvasive prenatal screening and array comparative genomic hybridization (aCGH) are disruptive technologies for prenatal diagnosis and screening, which have dramatically impacted the practice of obstetrics. Noninvasive prenatal screening utilization has decreased diagnostic procedures (DPs) by over 40%. Array comparative genomic hybridization has increased the diagnostic capabilities from fetal tissue. We have previously argued that increased use of aCGH would result in considerable economic savings in health care costs. What does this study add? Our procedures dropped 40%, but aCGH utilization has tripled. If DPs were stable with increased aCGH, we would have more than doubled abnormal copy number variant detection. Extrapolating nationally, if half the pregnancies in the United States had DPs, 30 000 currently undetected abnormal copy number variants could be found. The ratio of finding abnormalities to procedure complications is 8.5 to 1, which, from a public health perspective, many consider to be reasonable.