Rapid Genome Sequencing Identifies Treatable Conditions in Non-critically Ill Hospitalized Children
Health Services and Implementation
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Primary Categories:
- Health services and Implementation
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Secondary Categories:
- Health services and Implementation
Introduction:
The clinical utility of rapid genome sequencing (RGS) has been extensively evaluated in pediatric intensive care unit (ICU) settings, especially the neonatal ICU (NICU). Studies have demonstrated that arriving at a diagnosis faster has meaningful impacts on care for critically ill children. While RGS has become an accepted and common practice in neonatal and other pediatric ICUs, there is a paucity of studies exploring its value in non-critically ill hospitalized children. In the non-acute setting, testing strategies are often inconsistent, and can range from rapid comprehensive testing to a more gradual stepwise process. Understanding the utility of RGS outside of the ICU can impact providers’ decision-making as well as payor coverage.
Methods:
We reviewed the results of RGS ordered on a clinical basis in children admitted to Primary Children’s Hospital in Salt Lake City, Utah from 2019-2023. We compared diagnostic rates and testing indications in children admitted to an ICU (including neonatal, pediatric, and cardiac ICUs) and those not admitted to an ICU during their hospital stay. We also evaluated the impact of diagnostic test results on patient care in the non-ICU setting. Changes in management were determined via chart review focused on the first 30 days after testing. The 30-day time period was chosen to emphasize management changes that were made before a typical result time for non-rapid testing strategies.
Results:
444 individuals underwent RGS during the study period of 2019-2023; 361 in the ICU and 83 non-ICU. The diagnostic rate in non-ICU was 40% and 35% in ICU. Ages at testing were similar between the two groups. The majority of RGS in the non-ICU were ordered for neurologic symptoms. About 80% of non-ICU children with diagnostic RGS had a change in management within 30 days of testing, including medical interventions, referrals, or additional evaluation. Over half (56%) received a disease- targeted or -directed intervention including medication addition or adjustment, diet changes, initiation of a bone marrow transplant, or connection with a clinical trial. Of the children who received these intervention changes, the most common disease categories were metabolic (61%) and epilepsy (22%).
Conclusion:
RGS is effective at identifying treatable diagnoses in the non-ICU setting, with most patients experiencing a change in their care, and over half receiving disease- focused treatment. While some of these changes could have been initiated later following results of genetic testing on a more traditional timeline, we can expect that many patients would have deteriorated further and gained less benefit from their treatment if it had been delayed. Notably, nearly one-third of individuals had prior genetic testing such as a gene panel or microarray that was nondiagnostic. If they had received a diagnosis sooner, they could have received the appropriate interventions much earlier in their disease course, emphasizing the need for efficiency in genetic testing. In our study RGS identified multiple children with treatable inborn errors of metabolism. Within this disease classification, early treatment can prevent episodes of decompensation that lead to lifelong impairment. Ultimately, our results support the medical relevance of RGS in non-ICU hospitalized pediatric patients.
The clinical utility of rapid genome sequencing (RGS) has been extensively evaluated in pediatric intensive care unit (ICU) settings, especially the neonatal ICU (NICU). Studies have demonstrated that arriving at a diagnosis faster has meaningful impacts on care for critically ill children. While RGS has become an accepted and common practice in neonatal and other pediatric ICUs, there is a paucity of studies exploring its value in non-critically ill hospitalized children. In the non-acute setting, testing strategies are often inconsistent, and can range from rapid comprehensive testing to a more gradual stepwise process. Understanding the utility of RGS outside of the ICU can impact providers’ decision-making as well as payor coverage.
Methods:
We reviewed the results of RGS ordered on a clinical basis in children admitted to Primary Children’s Hospital in Salt Lake City, Utah from 2019-2023. We compared diagnostic rates and testing indications in children admitted to an ICU (including neonatal, pediatric, and cardiac ICUs) and those not admitted to an ICU during their hospital stay. We also evaluated the impact of diagnostic test results on patient care in the non-ICU setting. Changes in management were determined via chart review focused on the first 30 days after testing. The 30-day time period was chosen to emphasize management changes that were made before a typical result time for non-rapid testing strategies.
Results:
444 individuals underwent RGS during the study period of 2019-2023; 361 in the ICU and 83 non-ICU. The diagnostic rate in non-ICU was 40% and 35% in ICU. Ages at testing were similar between the two groups. The majority of RGS in the non-ICU were ordered for neurologic symptoms. About 80% of non-ICU children with diagnostic RGS had a change in management within 30 days of testing, including medical interventions, referrals, or additional evaluation. Over half (56%) received a disease- targeted or -directed intervention including medication addition or adjustment, diet changes, initiation of a bone marrow transplant, or connection with a clinical trial. Of the children who received these intervention changes, the most common disease categories were metabolic (61%) and epilepsy (22%).
Conclusion:
RGS is effective at identifying treatable diagnoses in the non-ICU setting, with most patients experiencing a change in their care, and over half receiving disease- focused treatment. While some of these changes could have been initiated later following results of genetic testing on a more traditional timeline, we can expect that many patients would have deteriorated further and gained less benefit from their treatment if it had been delayed. Notably, nearly one-third of individuals had prior genetic testing such as a gene panel or microarray that was nondiagnostic. If they had received a diagnosis sooner, they could have received the appropriate interventions much earlier in their disease course, emphasizing the need for efficiency in genetic testing. In our study RGS identified multiple children with treatable inborn errors of metabolism. Within this disease classification, early treatment can prevent episodes of decompensation that lead to lifelong impairment. Ultimately, our results support the medical relevance of RGS in non-ICU hospitalized pediatric patients.