Critically Ill Children Frequently Receive Medications with Established but Unused Pharmacogenomic Guidelines: Actionable Findings from an Integrated Electronic Medical Record and Exome Sequencing Study

Real prescriptions matched against metaboliser phenotypes derived from exome data; CYP2C9 is the most frequently implicated gene.

This retrospective cohort study links electronic medical record and exome sequencing data in a tertiary paediatric intensive care unit in New York. Among 4,939 children admitted between 2020 and 2024, 37.2% (n = 1,837) received at least one medication with established pharmacogenomic guidelines and 14.4% (n = 712) received two or more; twenty genes were implicated, led by CYP2C9 (17.3%, n = 853). The authors estimate that 8.2% of patients received medications for which genotype-guided prescribing would have altered clinical management. Among the 192 children with research exome sequencing, at least one metaboliser phenotype was identified in 62% (n = 119).

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The striking figure is the gap between exposure (37% of children) and actual use of genotype (none here): paediatric critical care is a blind spot for pharmacogenetics even though the therapeutic window is narrow. The second lesson is technical: only 62% of exomes yielded a metaboliser phenotype, a useful reminder that exome sequencing is not designed for pharmacogenetic genotyping and does not replace a dedicated panel. Preprint, single-centre and above all retrospective: the clinical impact remains estimated, not demonstrated.

Analysis by Dr Thibaut Benquey