904: Agreement to secondary findings with exome sequencing in pre- and postnatal settings

Abstract

The American College of Medical Genetics and Genomics (ACMG) recommends reporting variants in 59 clinically actionable genes when clinical exome sequencing (ES) is performed. However, prenatal and pediatric testing for these largely adult disorders is controversial, and their acceptance by families before versus after pregnancy is uncertain.We compared agreement to receiving secondary findings from prenatal versus pediatric ES in a large cohort. Families were recruited to a study of clinical utility of ES. Inclusion criteria were a non-diagnostic microarray, and either a fetal sonographic anomaly or in pediatric cases, a structural anomaly or developmental disorder. Families were counseled about secondary findings and given the choice to receive them. Trio ES (samples from proband and biological parents) was performed and results were reported to families, including secondary findings if requested. Chi square test and logistic regression were utilized as appropriate. 97 prenatal and 247 pediatric families were enrolled. In this diverse cohort, maternal ethnicities included 46% Latina, 37% White, 10% Asian, 4% Black, and < 1% each of other groups. In the prenatal group, median maternal age (MA) was younger (33 vs 36 years, p=.002), more had private insurance (78% vs 11%, p< .001), and interpreter utilization was lower (13% vs 46%, p< .001). Most families requested secondary findings, with no difference between prenatal and pediatric groups: 87% vs 80% (p=0.16). There was a trend toward MA affecting agreement: with each 5-year increase in MA, there were 10% decreased odds of requesting secondary findings (OR 0.9, 95% CI 0.7-1.1). A secondary finding was identified in 3% of ES (4 prenatal, 6 pediatric), with 2 secondary findings in one pediatric case. Although there are concerns about testing for adult disorders in prenatal and pediatric settings, most families agree to such testing and this agreement does not differ in the prenatal versus pediatric settings. Further research on patient decision-making in this context is needed.