ELSIcon2022 • Paper • May 27, 2022
Rebecca Mueller, Chris Feudtner, Katharine Callahan
Use of exome and genome sequencing are expanding in the neonatal intensive care unit with the goals of informing decision making and improving clinical management. These goals are together referred to as the “clinical utility” of genetic tests. However, meaningfully assessing clinical utility and aggregating this metric between different studies remain challenging. Here, we systematically review published studies of exome or genome sequencing in critically ill neonates and score reported clinical utility under five categories. Of the 20 studies that met eligibility criteria, 19 reported some measure of clinical utility. Criteria for assessing clinical utility varied between studies. Of 1605 patients included, 36% of patients tested had a positive result and 28% of patients met criteria for clinical utility. Genetic testing results informed recurrence risk for 36% of families (includes some with negative test results), prognosis for 19%, screening or subspecialty care for 12%, and medical treatment for 9%. Results led to redirection to palliative care for 6% of tested patients. One study included a parent-centered measure of utility. Studies with a smaller sample size were more likely to report higher utility. The current conception of clinical utility merges several testing consequences that are ethically and clinically distinct, and it rarely incorporates parents’ perspective. As exome and genome sequencing become commonplace among ill neonates, we need to understand not only whether a test changes management but the degree of impact and benefit.