730 - Genetic Diagnostic Odyssey for Critically-ill Infants: 10 years of experience in a level IV NICU

963 infants met inclusion criteria, of whom 433 were female (81.7%), with a median gestational age at birth of 37 weeks (interquartile range [IQR] 34-39 weeks), median age on NICU admission of 7 days (IQR 1-35 days) and median age at genetics consultation of 7 days (IQR 3-33 days). These factors were similar both pre- and post-rapid GS availability (Table). The overall diagnostic yield was 28.2% (272/963) with a median age at diagnosis of 37 days (IQR 23-68.5 days). Testing modalities leading to diagnosis included chromosome analysis (25, 9.2%), chromosomal microarray (46, 16.9%), single gene testing (64, 23.5%), gene panel sequencing (51, 18.8%), rapid GS (53, 19.5%), and other tests (33, 12.1%).

Median age at molecular diagnosis was significantly lower in the time period following rapid GS availability, though the diagnostic yield did not differ (Table). Similarly, identification of a genetic diagnosis was not significantly impacted by year of NICU admission (OR = 1.01, 95% C.I. 0.97 – 1.06, p = 0.58), though age at diagnosis significantly decreased by year of NICU admission (Β = -3.12 days, 95% C.I. -5.79 – -0.45, p = 0.02). The odds of a molecular diagnosis also increased by 12% for each increasing week of gestational age at birth (OR = 1.12, 95% C.I. 1.07 - 1.17).

Conclusion(s): Although availability of rapid GS was not associated with an increase in overall diagnostic yield, it was associated with a lower age at diagnosis, suggesting an opportunity for improved impact on clinical outcomes.