P1.172: Clinical and Personal Utility of Genetic Testing for Inpatient Neonates

Background: Genetic diseases are common in hospitalized neonates. Standardized utility measures to evaluate genetic testing in this population have only recently become available. Our study objectives were: 1) Evaluate the clinical and personal utility (CU, PU) of genetic testing for inpatient neonates as currently practiced in a setting with minimal restrictions on testing and 2) Identify testing strategies associated with the highest utility.

Methods: Interim analysis of a prospective observational cohort study from 7/1/2024-3/3/2025 including infants admitted < 28 days of age to any Nationwide Children’s Hospital service with genetic testing was conducted. Those discharged prior to at least one test resulting were excluded. An early broad (EB) testing strategy was defined by genome sequencing with results available within 14 days of admission. Data on the primary provider’s global impression of genetic testing CU was captured 2-14 days after result return for each test individually. Validated measures of PU (GENEU) and psychosocial impact (FACToR) plus a global PU item were obtained from the caregiver(s) after infant discharge. Associations of CU with testing strategy, indication, and outcome were evaluated with logistic regression. The same associations were evaluated with linear model estimates for PU. Within household variation of PU for infants where multiple caregivers completed surveys was examined as well as association of CU and PU using Fishers exact test.

Results: There were 109 infants included in the interim analysis (Figure 1). Of these, 25% (n=27) with 52 genetic tests underwent an EB strategy. Twenty-eight percent (n=31) of infants received a genetic diagnosis. Males were overrepresented in the EB group compared to other testing strategies (70% vs. 48%). Most testing was sent from the neonatal intensive care unit (ICU; 72%) followed by the cardiac ICU (25%). The most common indication for testing was multiple anomalies. Indications other than multiple anomalies and an EB testing strategy showed relatively higher CU, however this did not reach statistical significance. Odds of positive CU were higher when at least one test was diagnostic (odds ratio 10; 95% CI, 2.4-70). There was no association with GENEU total score and testing strategy, diagnostic outcome, or testing indication. Examination of the global impression of PU revealed a higher percentage of caregivers of EB infants felt genetic testing was beneficial compared to other strategies (63% vs. 54%). Having a child with a diagnosis was associated with a 10-point increase in FACToR. Results from 16 households where both caregivers completed GENEU & FACToR showed some variation (Figure 2). Global CU and global PU were associated (p < 0.05).

Conclusion: An EB testing strategy may provide high CU and PU. Families and providers generally agree regarding utility of genetic testing. Pediatricians should anticipate psychosocial impacts when genetic diagnoses are made in the hospital.