Perinatal outcomes and genomic characteristics of fetal copy number variants: An individual record linkage study of 713 pregnancies

Abstract

AbstractObjectiveTo determine the perinatal outcomes of fetuses diagnosed with a pathogenic copy number variant (CNV) or variant of uncertain significance (VUS); and to characterize these variants in terms of testing indication, genomic location, size, and inheritance.MethodsRetrospective study of singleton pregnancies with a pathogenic CNV or VUS from a single laboratory during 2012–2018. Probabilistic record linkage between the prenatal diagnosis dataset and perinatal outcome data for births from 20 weeks gestation was performed. If no birth record was found, this implied a pregnancy loss <20 weeks.ResultsWe included 6945 prenatal microarray results; a pathogenic CNV was detected in 230 (3.3%, 95% CI: 2.9%–3.8%) and a VUS in 483 (7.0%, 95% CI: 6.4%–7.6%). Of pregnancies with a pathogenic CNV, 20.0% (95% CI: 15.3%–25.6%) had a live birth, 3.0% (95% CI: 1.5%–6.2%) had a perinatal death (stillbirth or neonatal death), and 77% (95% CI: 71.1%–81.9%) had no birth record. Of those with a VUS, 64.4% (95% CI: 60.0%–68.5%) had a live birth, 1.8% (95% CI: 1.0%–3.5%) had a perinatal death, and no birth record was found for 33.7% (95% CI: 29.7%–38.1%). Most pathogenic CNVs (61.1%) were <7 Mb in size. The most common microdeletion syndromes were DiGeorge, Wolf‐Hirschhorn, and Cri‐du‐chat syndromes.ConclusionThis study provides an overview of perinatal outcomes and frequency of recurrent CNVs observed in the prenatal microarray era.