A study of 112 infant deaths found that 41% were associated with a genetic disease, a higher rate than previously recognized, according to a study published in JAMA Network Open.

The cohort study was conducted by researchers at Rady Children’s Institute for Genomic Medicine at the University of California, San Diego. Co-authorStephen Kingsmore, MD, president and CEO of the institute, told Healio that his team has worked for a decade to decode infants’ genomes.

“What we did was to develop the world’s fastest genetic disease diagnostic test, and we can return a result within a day,” Kingsmore said. “Over the last 10 years, this has become more and more established as a routine test for babies in ICUs, and we’ve tested thousands of babies in hundreds of hospitals around North America. Typically, we diagnose about one in three babies. If they have some kind of illness, we decode their genome [and see if] we find a genetic cause.”

The aim of the current study was to understand how common genetic diseases are in babies who die during the first year of life.

“Every baby who dies has a death certificate, and that’s filled out to the doctor’s best ability in terms of what caused the baby’s death,” Kingsmore said. “But most of those babies don’t get a genome sequence. We saw the proportion of babies who were thought to die of a genetic disease be vastly underrepresented, and that’s really important because knowing what causes infant mortality unleashes a huge amount of resources to try to combat that.”

The study included 546 infants born between January 2015 and December 2020 — 112 who died and 434 who had an acute illness but survived. All infants underwent diagnostic whole-genome sequencing either pre- or post-mortem.

Ultimately, the researchers found that single-locus genetic diseases were the most common identifiable cause of infant mortality, with 47 genetic diseases identified in 46 infants (41%). Treatments were available for 30% of the diseases detected. Of the deceased infants, 28 death certificates (62%) for 45 of the 46 infants did not mention a genetic etiology.

Co-author Christina Chambers, PhD, MPH, vice chair of clinical research for the department of pediatrics at Rady Children’s, told Healio that “whole-genome sequencing leads to identification of about one-third of the causes of serious disabilities in children.”

“The novel finding here is that we were able to demonstrate for the most serious outcome — ie, infant death — that a high proportion could be attributed to underlying genetic disease, and most importantly, that some of these conditions are and could have been treatable,” Chambers said.

“Genetic diseases, we find, at least in this population, are the leading causes of infant death and accounted for 41% — just an astounding figure that nobody had recognized previously,” Kingsmore said.

Death could be avoided by conducting whole-genome sequencing early in life for every infant.

“Whole genome sequencing early in life, even at time of newborn screening, could lead to prevention of serious consequences of genetic diseases that now or in the near future have available effective treatments,” Chambers said.

“These are the babies who nobody was thinking about genetic disease, no genetic testing was ordered,” Kingsmore said. “Even in that set of babies, we find that genetic diseases were the leading cause of death, and about half of them had effective treatments. That really was mind shattering for us all to realize that a lot of babies are dying unnecessarily.”