Large scale studies of whole genome sequencing (WGS) in neonates have largely been neglected. Thus, its clinical and social implications are largely unknown. The proposed study aims to increase scientific knowledge of these implications for acutely ill neonates. This population may stand to benefit largely from WGS given the severity of illness. The proposed clinical study is a prospective, randomized, partially blinded study which has both quantitative and qualitative assessments of the risks and benefits of the use of STATseq, a 2-day genome test, in acutely ill neonates at Children's Mercy Hospital. Study participants include neonates, their parents and clinicians caring for them. The overall aims will provide a nuanced understanding of the role of rapid diagnostic WGS for acutely ill neonates, including relative diagnostic sensitivity and change in management both for broad NICU populations and subpopulations, accuracy, reproducibility, and relative value of proband WGS and familial triads. The technologic aims include improving diagnostic sensitivity without sacrificing the rapid turnaround time. The clinical aims include looking at increased diagnostic yield, shorter time to diagnosis and clinician perception of management changes that result from implementation of STAT-seq. Finally, the study will investigate the perceived value of STAT-seq in parents and clinicians using structural equation modeling. The studies also are designed for long term continuation of assessment of the enrollees (beyond the current funding period) and in additional sample types (via a bio repository). Long term continuation studies will test effects on long term morbidity, mortality, quality of life and cost of care. We hope that the study results will be sufficient to provide an evidence base for physician adoption and provider reimbursement of WGS in Level 3 and 4 NICUs.

Public Health Relevance

6.7% of newborns require care in a neonatal intensive care unit and this group has the highest morbidity and mortality of any pediatric group. Given the severity of illness, these newborns may have the most to gain from fast genetic diagnosis through the use of whole genome sequencing. Thus, we propose to examine the benefits and risk of rapid WGS technology in this population.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Program--Cooperative Agreements (U19)
Project #
3U19HD077693-04S1
Application #
9256676
Study Section
Special Emphasis Panel (ZHD1)
Program Officer
Parisi, Melissa
Project Start
2013-09-05
Project End
2018-08-31
Budget Start
2015-09-03
Budget End
2016-08-31
Support Year
4
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Rady Pediatric Genomics & Systems Medicine Institute
Department
Type
DUNS #
136123085
City
San Diego
State
CA
Country
United States
Zip Code
92123
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