Zachary Daniels, MD, MS
Assistant Professor Pediatric Critical Care
Children's Hospital of New Orleans
New Orleans, Louisiana
Disclosure information not submitted.
Kevin Morrison
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois
Disclosure information not submitted.
L. Nelson Sanchez-Pinto, MD, MBI
Assistant Professor of Pediatrics (Critical Care)
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois
Disclosure information not submitted.
Divakar Mithal, MD, PhD
Instructor of Pediatrics (Neurology)
Ann & Robert H. Lurie Children's Hospital of Chicago / Northwestern University Feinberg School of Medicine, United States
Disclosure information not submitted.
Title: Association of Whole Exome Sequencing with Severity of Illness in the Pediatric ICU
Introduction:
Genetic etiologies of pediatric disease represent an increasing proportion of pediatric intensive care unit (PICU) admissions due to more accessible diagnostic and therapeutic techniques. These patients demonstrate higher average lengths of stay, readmission rates and mortality rates than the broader PICU population. The present study aims to better describe this paradigm by examining the association between whole exome sequencing (WES) and illness severity in the PICU setting. The central hypothesis is that if a PICU patient has ever had WES performed, then they will carry a higher disease burden on admission than other PICU patients.
Methods:
A retrospective cohort study was performed utilizing an institutional database of PICU admissions over a ten-year period, comprising 12,554 unique patients. Individuals with a PICU admission within this timeframe who had WES performed at any point were identified. Illness severity was defined utilizing the PRISM III score on admission. The scores of patients with WES were compared to the scores of the general PICU population without WES. Statistical differences were quantified via a Mann-Whitney U test.
Results:
Of 12,554 total patients with a PICU admission between August 2010 and October 2020, 115 had WES performed at any time. These patients had a median PRISM III score of 5 (IQR 2, 9) at the time of their first admission compared to a median of 3 (IQR 0, 7) in the general PICU population (p < 0.001). Comparing all admissions for each patient, those with WES performed demonstrated a higher median PRISM III score of 7 (IQR 3, 12) relative to the general PICU population median of 3 (IQR 0, 8) (p < 0.001). Of patients with WES performed, 83% had one or more positive genotypic findings. Within this subgroup, 61% had one or more pathogenic or likely pathogenic findings compared to 34% with solely variants of uncertain significance.
Conclusions:
Relative to the general PICU population, patients with whole exome sequencing performed at any time demonstrate a more significant degree of illness severity on admission as quantified via the PRISM III score both at the time of initial presentation and across all admissions. Early identification of patients for whom WES is indicated presents an opportunity to improve clinical management and resource utilization.