Capturing the clinical utility of genomic testing: medical recommendations following pediatric microarray

Interpretation of pediatric chromosome microarray (CMA) results presents diagnostic and medical management challenges. Understanding management practices triggered by CMA will inform clinical utility and resource planning. Using a retrospective cohort design, we extracted clinical and management-related data from the records of 752 children with congenital anomalies and/or developmental delay who underwent CMA in an academic pediatric genetics clinic (2009-2011). Frequency distributions and relative rates (RR) of post-CMA medical recommendations in children with reportable and benign CMA results were calculated. Medical recommendations were provided for 79.6% of children with reportable results and 62.0% of children with benign results. Overall, recommendations included specialist consultation (40.8%), imaging (32.5%), laboratory investigations (17.2%), surveillance (4.6%), and family investigations (4.9%). Clinically significant variants and variants of uncertain clinical significance were associated with higher and slightly higher rates of management recommendations, respectively, compared with benign/no variants (RR=1.34; 95% CI (1.22-1.47); RR=1.23; 95% CI (1.09-1.38)). Recommendation rates for clinically significant versus uncertain results depended upon how uncertainty was classified (RRbroad=1.09; 95% CI (0.99-1.2); RRnarrow=1.12; 95% CI (1.02-1.24)). Recommendation rates also varied by the child's age and provider type. In conclusion, medical recommendations follow CMA for the majority of children. Compared with benign CMA results, clinically significant CMA variants are a significant driver of pediatric medical recommendations. Variants of uncertain clinical significance drive recommendations, but to a lesser extent. As a broadening range of specialists will need to respond to CMA results, targeted capacity building is warranted.