1. Measurement of genetic diseases as a cause of mortality in infants receiving whole genome sequencing
- Author
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David Dimmock, Audrey Henderson, Christian Hansen, Christina D. Chambers, Charlotte A. Hobbs, Stephen F. Kingsmore, Laura Jeliffe-Pawlowski, Mallory J Owen, and Michelle M. Clark
- Subjects
0301 basic medicine ,Pediatrics ,medicine.medical_specialty ,lcsh:QH426-470 ,lcsh:Medicine ,Article ,03 medical and health sciences ,0302 clinical medicine ,Clinical Research ,Locus heterogeneity ,Secondary analysis ,Infant Mortality ,Genetics ,medicine ,Molecular Biology ,Genetics (clinical) ,Public health policy ,Pediatric ,Whole genome sequencing ,Molecular medicine ,business.industry ,Genomic sequencing ,Human Genome ,lcsh:R ,medicine.disease ,Infant mortality ,lcsh:Genetics ,Good Health and Well Being ,030104 developmental biology ,Systematic review ,business ,030217 neurology & neurosurgery - Abstract
Understanding causes of infant mortality shapes public health policy and prioritizes diseases for investments in surveillance, intervention and medical research. Rapid genomic sequencing has created a novel opportunity to decrease infant mortality associated with treatable genetic diseases. Herein, we sought to measure the contribution of genetic diseases to mortality among infants by secondary analysis of babies enrolled in two clinical studies and a systematic literature review. Among 312 infants who had been admitted to an ICU at Rady Children’s Hospital between November 2015 and September 2018 and received rapid genomic sequencing, 30 (10%) died in infancy. Ten (33%) of the infants who died were diagnosed with 11 genetic diseases. The San Diego Study of Outcomes in Mothers and Infants platform identified differences between in-hospital and out-of-hospital causes of infant death. Similarly, in six published studies, 195 (21%) of 918 infant deaths were associated with genetic diseases by genomic sequencing. In 195 infant deaths associated with genetic diseases, locus heterogeneity was 70%. Treatment guidelines existed for 70% of the genetic diseases diagnosed, suggesting that rapid genomic sequencing has substantial potential to decrease infant mortality among infants in ICUs. Further studies are needed in larger, comprehensive, unbiased patient sets to determine the generalizability of these findings.
- Published
- 2020