Mother and preterm baby first touch
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Rapid, whole-genome sequencing (WGS) of critically ill infants when integrated with transcriptomic and functional data can provide for rapid diagnoses and improvements in care, according to an abstract of an Australian study presented Sunday at the European Society of Human Genetics (ESHG). The data, the researchers suggest could be used as a national model to improve the care of severely ill infants.

“The evidence of diagnostic, clinical, and family benefit of rapid genomic testing in critically ill children is overwhelming. This type of testing should become the standard of care for these patients,” said the presenter, Prof. Zornitza Stark, a clinical geneticist at the Victorian Clinical Genetics Services and Australian Genomics. “And rapid genomic diagnosis programs should continue to drive improvement, innovation, and discovery more broadly.”

WGS has gained significant traction as a vital tool to help diagnose critically ill newborns, driven in the US by the cutting edge work of Stephen Kingsmore at Rady Children’s Institute for Genomic Medicine (RCIGM), which has seen its program spread to other health systems across the country.

In this recent nationwide study in Australia, the researchers preform rapid WGS on 290 critically ill infants between January of 2020 and January of 2022, with an aim of providing results and, ultimately, a diagnosis within five days. The researchers were able to provide a diagnosis for 136—or roughly 47%—of the infants with an average time to diagnosis of less than three days. Of the 154 patients not diagnosed via the standard WGS methods, another 20 diagnoses were delivered via other test methods including RNA sequencing. Further, new rare disease-causing genetic variants were identified by leveraging international matchmaking databases.

“We wanted the program to serve as an exemplar of how genomics can improve diagnostic and clinical outcomes in pediatric disease in real time,” Stark noted. “We have now incorporated RNA sequencing and, through close collaboration with clinicians and researchers, optimized the use of functional data to secure additional diagnoses.”

The researchers note that while the cost of a rapid sequencing approach remains high compare with other diagnostic approaches, the quick diagnoses delivered via NGS can provide saving to health system on a long-term basis. Data developed by the RCIGM team in the US detailed the savings via a research partnership called Project Baby Bear it launched in 2018 with the California state Medicaid program. Run at five hospitals across the state, the researchers sequenced 178 babies, provided diagnoses for 76 babies (43%), and saved the insurance program $2.5 million dollars.

Building this capability in a health system does require some effort, Stark added, as this kind of program requires a multi-disciplinary team and also clinical labs that have both the capability via a trained workforce and the capacity to perform such testing.

“Our approach can serve as a model in other healthcare systems, although it will need to be adapted to local circumstances and to evolve over time. For example, Australia has a very geographically dispersed population, which is relatively small compared to the land area. It made sense for us to have a central sequencing laboratory for this study, with a lot of attention paid to sample transport logistics and to including local teams in analysis through virtual meetings. Different models will be needed in countries with high population density.”

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