Genet Med Open. 2025 Oct 13;3:103464. doi: 10.1016/j.gimo.2025.103464. eCollection 2025.
ABSTRACT
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 2 years.
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. We assessed a range of cognitive, developmental, and health outcomes in the children, who were on average 6 years old. 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 behavior, 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.
CONCLUSION: 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 counseling and clinical laboratory reporting practices.
PMID:41362834 | PMC:PMC12681968 | DOI:10.1016/j.gimo.2025.103464
