A newborn in the hospital's maternity ward
Catherine Delahaye/ Getty Images Stone

Whole-genome sequencing (WGS) could prevent babies dying from treatable genetic diseases, a U.S. study suggests.

WGS implicated single-locus genetic diseases in four out of every 10 deaths among infants at a large Californian pediatric hospital system over a five-year period.

Yet more than half of the death certificates made no mention of a genetic cause, the researchers report in the journal JAMA Open.

Importantly, they note that treatments that could improve outcomes were available for nearly a third of the genetic diseases identified.

“Broader use of rapid diagnostic WGS in a learning health care system of genome-informed neonatology may be associated with substantially reduced U.S. infant mortality,” predict Mallory Owen, from Rady Children’s Hospital in San Diego, and co-workers.

Infant mortality in the U.S. remains high at approximately one in every 200 live births, with congenital malformations and chromosomal abnormalities accounting for a fifth of these deaths.

Genomic sequencing has identified single-locus diseases are a leading cause of mortality in some categories, such as sudden infant death syndrome (SIDS), but their overall association with infant mortality is not well quantified.

To investigate further, the researchers studied 311 available health records from 940 infants who died (0.39% of live births) in a single pediatric hospital system in San Diego County between 2015 and 2020.

Of these, 112 underwent WGS either as a rapid, inpatient diagnostic test (59.8%) or postmortem using archived dried blood spots (50.2%).

WGS identified 47 single-locus genetic diseases in 46 infant deaths (41%).

Among the 47 genetic diseases identified, 39 (83%) had previously been reported to be associated with childhood mortality and treatments that could improve outcomes were available for 14 (30%).

The team notes that 28 death certificates (62%) for 45 of the 46 infants did not mention genetic etiology.

In five of seven infants for 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.

Of 21 maternal and infant characteristics examined, five known risk factors for infant death differed significantly between the 46 infant deaths associated with genetic diseases and 66 without.

Premature birth, placental abruption, and maternal infection were more common in infant deaths without genetic diseases, while polyhydramnios—in which there is too much amniotic fluid around the baby during pregnancy—was more common in deaths associated with genetic diseases.

“Whole-genome sequencing materially changed the etiology of four leading causes of infant mortality (congenital malformations/chromosomal abnormalities, SIDS, sepsis, and respiratory distress) and ‘all others,’ which together comprised 71% of deaths,” the authors note.

“We recommend inclusion of the molecular etiology in the national vital statistics of these four leading causes of infant mortality.

“This is likely to reprioritize public health and research programs to combat infant mortality.”

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