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. 2023 Feb 1;6(2):e2254069.
doi: 10.1001/jamanetworkopen.2022.54069.

Reclassification of the Etiology of Infant Mortality With Whole-Genome Sequencing

Mallory J Owen  1   2 , Meredith S Wright  1 , Sergey Batalov  1 , Yonghyun Kwon  1 , Yan Ding  1 , Kevin K Chau  1 , Shimul Chowdhury  1 , Nathaly M Sweeney  1   2 , Elizabeth Kiernan  1 , Andrew Richardson  1 , Emily Batton  2 , Rebecca J Baer  2   3 , Gretchen Bandoli  2 , Joseph G Gleeson  1   2 , Matthew Bainbridge  1 , Christina D Chambers  2 , Stephen F Kingsmore  1
Affiliations

Reclassification of the Etiology of Infant Mortality With Whole-Genome Sequencing

Mallory J Owen et al. JAMA Netw Open. .

Abstract

Importance: Understanding the causes of infant mortality shapes public health, surveillance, and research investments. However, the association of single-locus (mendelian) genetic diseases with infant mortality is poorly understood.

Objective: To determine the association of genetic diseases with infant mortality.

Design, setting, and participants: This cohort study was conducted at a large pediatric hospital system in San Diego County (California) and included 546 infants (112 infant deaths [20.5%] and 434 infants [79.5%] with acute illness who survived; age, 0 to 1 year) who underwent diagnostic whole-genome sequencing (WGS) between January 2015 and December 2020. Data analysis was conducted between 2015 and 2022.

Exposure: Infants underwent WGS either premortem or postmortem with semiautomated phenotyping and diagnostic interpretation.

Main outcomes and measures: Proportion of infant deaths associated with single-locus genetic diseases.

Results: Among 112 infant deaths (54 girls [48.2%]; 8 [7.1%] African American or Black, 1 [0.9%] American Indian or Alaska Native, 8 [7.1%] Asian, 48 [42.9%] Hispanic, 1 [0.9%] Native Hawaiian or Pacific Islander, and 34 [30.4%] White infants) in San Diego County between 2015 and 2020, single-locus genetic diseases were the most common identifiable cause of infant mortality, with 47 genetic diseases identified in 46 infants (41%). Thirty-nine (83%) of these diseases had been previously reported to be associated with childhood mortality. Twenty-eight death certificates (62%) for 45 of the 46 infants did not mention a genetic etiology. Treatments that can improve outcomes were available for 14 (30%) of the genetic diseases. In 5 of 7 infants in whom genetic diseases were identified postmortem, death might have been avoided had rapid, diagnostic WGS been performed at time of symptom onset or regional intensive care unit admission.

Conclusions and relevance: In this cohort study of 112 infant deaths, the association of genetic diseases with infant mortality was higher than previously recognized. Strategies to increase neonatal diagnosis of genetic diseases and immediately implement treatment may decrease infant mortality. Additional study is required to explore the generalizability of these findings and measure reduction in infant mortality.

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Conflict of interest statement

Conflict of Interest Disclosures: All authors reported grants from the National Institutes of Health (NIH).

Figures

Figure.
Figure.. Flow Diagram of the Observational Study of Infant Survivors and Infants Who Died Who Underwent Whole-Genome Sequencing (WGS) for Diagnosis of Genetic Diseases During Care at Rady Children’s Hospital, San Diego, California, from 2015 to 2020
The left side of the diagram represents 45 infant deaths who received WGS postmortem and 67 who received rapid WGS for diagnosis of a suspected genetic disease during intensive care unit (ICU) admission. The right side of the diagram represents the control group, comprising infant survivors who received rapid WGS for diagnosis of a suspected genetic disease during ICU admission. a2020 deaths projected from average of 2015 to 2019 total deaths. bStandard genetic tests included chromosomal microarray, gene, and panel sequencing. cThe efficacy of interventions for diseases associated with infant mortality in this study was adjudicated with the Genome-to-Treatment system and a similar online compendium of treatable genetic disorders.,
See this image and copyright information in PMC

References

    1. Ely DM, Driscoll AK. Infant mortality in the United States, 2018: data from the period linked birth/infant death file. Natl Vital Stat Rep. 2020;69(7):1-18. - PubMed
    1. Murphy SL, Xu J, Kochanek KD, Arias E. Mortality in the United States, 2017. NCHS Data Brief. 2018;328(328):1-8. - PubMed
    1. Xu J, Kochanek KD, Murphy SL, Tejada-Vera B. Deaths: final data for 2007. Natl Vital Stat Rep. 2010;58(19):1-19. - PubMed
    1. Hoyert DL, Kochanek KD, Murphy SL. Deaths: final data for 1997. Natl Vital Stat Rep. 1999;47(19):1-104. - PubMed
    1. US Centers for Disease Control and Prevention . Vital statistics of the United States, 1979. Accessed January 20, 2023. https://www.cdc.gov/nchs/data/vsus/mort79_2a.pdf

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