Abstracts

Rationale: Genetic testing is increasingly utilized in neonatal intensive care units (NICU) to diagnose the etiology of neonatal onset seizures. Since 2018, the landscape of testing has changed due to the availability of Next Generation Sequence (NGS) sponsored genetic testing. The benefits of this method on hospital and short-term outcomes are unknown. We sought to describe the evolution of genetic testing practices for neonatal onset seizures over an 8-year period among a cohort of NICU patients in a single institution, and characterize differences in hospital and short-term outcomes with the use of NGS sponsored genetic testing using non-parametric statistical analysis.

Methods: Medical records of neonates admitted to Lurie Children’s Hospital NICU between 2012 – 2020 were reviewed. Cases were included if they presented with neonatal onset epilepsy and had genetic testing performed during their hospital stay. Cases with acute symptomatic seizures, or genetic testing done only after discharge were excluded. Data collected included: demographic and gestational characteristics, genetic tests ordered, and turnaround time, findings, and time to discovery of a pathogenic genetic finding. Genetic testing included microarrays, single gene testing, karyotype, whole exome sequencing (WES), and NGS panels. Length of stay (LOS), family history, imaging studies and antiseizure medications (ASMs) during admission and discharge were all reviewed. Short term discharge outcomes (use of tracheostomy, and tube feedings) were ascertained. We compared hospital and short-term outcomes after the introduction of NGS sponsored genetic testing using non-parametric statistical tests (Mann-Whitney test) before and after 2018.

Results: Fifty-three infants (51% female) were included; 33 infants pre-2018 and 20 post-2018. The race/ethnicity distribution was 37.7% White, 26.4% Black, 7.5% Asian and 28.3% other (inclusive of Hispanic). Microarray analysis was performed in 25 with 24% yield of positive findings, single gene tests in 12 (67% yield), karyotype analysis in 5 (20% yield), NGS panel sequencing in 38 (32% yield), and WES in 7 (71% yield). SCN2A accounted for 21%, KCNQ3 for 10%, GLDC for 10% and microduplications/microdeletions for 14% of all pathogenic findings. Median LOS was 22 days for all neonates (Interquartile range 13 to 56). When compared, the median LOS (32 vs. 17 days, p=0.03), time to molecular diagnosis (51 vs. 17 days, p=0.003), and age at molecular diagnosis (74 vs 27 days, p=0.02) were significantly different prior to versus after the introduction in 2018 of NGS sponsored genetic testing. The number of tests (2 vs. 1, p=0.08), number of ASMs at discharge (2 vs. 1, p=0.1), and use of tracheostomy (p >0.99) or tube feedings (p=0.776) were not significantly different.

Conclusions: In this cohort, the time to molecular diagnosis fell significantly after 2018 when sponsored genetic testing was introduced. Results also suggest differences in shorter LOS, fewer tests, and earlier age at diagnosis. Replication of this study in a larger, multicenter sample size is needed.

Funding: Please list any funding that was received in support of this abstract.: None.