NEW YORK – Investigators at the Tel Aviv Sourasky Medical Center, Tel Aviv University, and other centers in Israel have demonstrated that rapid trio genome sequencing (rtGS) performed in a public healthcare context may be a feasible and effective strategy to help diagnose genetic conditions in infants treated in neonatal intensive care units.
"To our knowledge, we have conducted the first prospective national pilot of [rapid trio genome sequencing] as a single test for genomic diagnosis in critically ill neonates," senior and corresponding author Daphna Marom, a researcher at the Tel Aviv Sourasky Medical Center's Genetics Institute and Genomics Center, and colleagues wrote in a paper published in JAMA Network Open on Thursday.
For the prospective study, conducted through Israel's universal healthcare system, researchers at Tel Aviv Sourasky Medical Center's central genomics site performed rtGS on 130 critically ill neonates with suspected genetic conditions, along with their parents. The group, dubbed the "Baby Bambi" cohort, was enrolled at 18 medical genetics institutes and 25 neonatal intensive care units in Israel between October 2021 and December 2022.
"In public healthcare systems, limited resources challenge the widespread implementation of advanced sequencing technologies into routine inpatient clinical practice," the authors wrote, adding that the current study "is a prerequisite for implementation of rtGS for ill neonates into routine care and may aid in design of similar studies in other public healthcare systems."
The team aimed to have results available within 10 days for each case and achieved a mean turnaround time of seven days between sampling and returning an initial rapid report. The infants were 12 days old, on average, at the time of enrollment in the study.
The genome data revealed disease-causing pathogenic or likely pathogenic variants in 65 of the infants, the researchers reported, including 51 single-nucleotide changes, 12 copy number variants or chromosomal disorders, one triplet repeat expansion, and one case of uniparental disomy.
They also uncovered variants of uncertain significance in 15 more cases. One of these involved a CNV, while the remaining 14 were single-nucleotide variants falling in known or novel candidate genes.
Based on their findings, the authors suggested that "rtGS in critically ill neonates was feasible and diagnostically beneficial in a public healthcare setting."
Along with their primary analyses, which focused on rtGS feasibility and diagnostic utility in the NICU setting, the investigators also performed secondary analyses focused on precision medicine and recurrence risk reduction.
The team's clinical utility questionnaires garnered responses from 82 percent of families, for example, with two dozen families describing medical management changes for their children based on the genomic test results. Half a dozen of those infants gained access to precision medicine options, while two children were subsequently transferred to nursing homes and two went on to receive palliative care.
In a corresponding commentary, Shan Jiang and colleagues from Macquarie University, who were not involved in the study, noted that the results not only highlight the potential for effectively applying rtGS in the public healthcare context but also point to the potential benefits of applying the approach to neonatal care more routinely.
"By offering tailored treatments at an early stage, genome sequencing not only enhances the quality of care but also holds the promise of improving long-term health outcomes, as evidenced by empirical studies," the authors wrote, noting that this "highlights the increasingly critical role of genome sequencing in the dynamic landscape of neonatal healthcare."