Infant Mortality

Infant mortality is one of the leading indicators of a nation’s health. We seek to better understand which infant deaths are linked to genetic diseases. That information can then be used to focus resources to improve diagnosis and treatment for those conditions.

In 2020, RCIGM and UC San Diego were jointly awarded a $3.6M, 5-year grant to study infant mortality from the NIH Eunice Kennedy Shriver National Institute of Child Health and Human Development.


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Researchers plan to decode genomes associated with 1,000 infant deaths from dried blood spots. By combining data about the genetic makeup of these infants with data about their environment, birth, and demographic risk factors they will examine the roles these different factors play in infant mortality. The goal is to detect the causes of previously unexplained deaths and use that to inform prevention and intervention strategies.

The study will also probe the ethical implications of returning results to bereaved families.

Research Study

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Christina Chambers, PhD, MPH

UC San Diego

San Diego, CA, Aug. 21, 2017-- Dr. Stephen Kingsmore.  Photo by Earnie Grafton.

Stephen Kingsmore, MD, DSc

Rady Children's Institute for Genomic Medicine


Am J Hum Genet. 2023 Jun 1;110(6):1017. doi: 10.1016/j.ajhg.2023.05.004.


PMID:37267897 DOI:10.1016/j.ajhg.2023.05.004

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


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.

PMID:36757698 DOI:10.1001/jamanetworkopen.2022.54069

Annu Rev Genomics Hum Genet. 2022 Jun 8. doi: 10.1146/annurev-genom-120921-103442. Online ahead of print.


Genetic diseases disrupt the functionality of an infant’s genome during fetal-neonatal adaptation and represent a leading cause of neonatal and infant mortality in the United States. Due to disease acuity, gene locus and allelic heterogeneity, and overlapping and diverse clinical phenotypes, diagnostic genome sequencing in neonatal intensive care units has required the development of methods to shorten turnaround times and improve genomic interpretation. From 2012 to 2021, 31 clinical studies documented the diagnostic and clinical utility of first-tier rapid or ultrarapid whole-genome sequencing through cost-effective identification of pathogenic genomic variants that change medical management, suggest new therapeutic strategies, and refine prognoses. Genomic diagnosis also permits prediction of reproductive recurrence risk for parents and surviving probands. Using implementation science and quality improvement, deployment of a genomic learning healthcare system will contribute to a reduction of neonatal and infant mortality through the integration of genome sequencing into best-practice neonatal intensive care. Expected final online publication date for the Annual Review of Genomics and Human Genetics, Volume 23 is October 2022. Please see for revised estimates.

PMID:35676073 | DOI:10.1146/annurev-genom-120921-103442

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