EP03.02: Long‐term developmental outcomes of children with a prenatal diagnosis of a variant of uncertain significance: the PrenatAL Microarray (PALM) study

Chromosomal microarrays are now the standard method of assessing fetal karyotype after a prenatal diagnosis of a structural anomaly, but can yield uncertain results. We aimed to compare the developmental outcomes of children with a prenatal diagnosis of a variant of uncertain significant (VUS; cases) with those children who had a no copy number variant on prenatal chromosomal microarray and who did not have a fetal structural anomaly as the indication for diagnostic testing (controls). Women residing in Victoria, Australia, who had a prenatal chromosomal microarray between 2013-2019 and a live birth outcome of a singleton infant were retrospectively recruited. Comparisons between cases and controls were made using t and χ2 tests on developmental outcomes including intellectual functioning, adaptive functioning, and social communication behaviours. A total of 113 mother-child pairs completed the full range of clinical assessments (30 VUS cases, and 83 controls). The mean age of children at the time of assessment was 6.0 years (SD = 1.8); 53.4% (n = 62) were male. Compared with controls, children with a VUS did not have a significant difference in overall intellectual function, adaptive functioning, or behaviours associated with autism spectrum disorder. Children in the VUS group performed significantly lower on verbal comprehension tasks compared to children in the control group (mean score = 95.5 vs. 105.1, p = .003), but both scores remained within the average range. Mothers in the VUS group were significantly younger at the time of giving birth than the control group (33.5 vs. 36.6 years, p = .004). Our results provide the first comprehensive long-term outcomes to inform genetic counselling after a prenatal diagnosis of an uncertain genomic variant. In our cohort of children, a prenatal diagnosis of a VUS was not associated with clinically meaningful differences in cognitive abilities, adaptive living skills, or social behaviours.