Childhood outcomes of fetal genomic copy number variants: the prenatal microarray cohort study

Purpose The long-term developmental outcomes of children with a prenatal diagnosis of a copy number variant of uncertain significance (VUS) remain unclear. This study compared the developmental, social-emotional, and health outcomes of children with and without a prenatal VUS, assessed maternal perceptions of their child’s health and development, and examined the reclassification rate of VUS after more than two years. Materials and Methods Women who underwent prenatal chromosomal microarray testing in Victoria, Australia (2013–2019), were recruited retrospectively (2021–2023). Children with a VUS (cases) were compared with controls without a VUS. Outcomes, including cognitive, developmental, and health measures, were assessed and children had an average age of six years. Statistical analyses compared group outcomes and adjusted for maternal sociodemographic factors. Results The study included 134 mother-child pairs (46 with a VUS and 88 controls). No significant differences were found between groups in intellectual functioning, adaptive behaviour, or social-emotional measures. Maternal perceptions of their child and family well-being were also similar. Reanalysis reclassified 66.0% of VUS as benign and 8.5% as pathogenic. Conclusions Children with a prenatal VUS diagnosis have developmental outcomes and family well-being comparable to those without. These findings contribute valuable evidence to support prenatal genetic counselling and clinical laboratory reporting practices. Observational study registration: ACTRN12620000446965p; Registered on April 6, 2020.