Genet Med. 2026 Jun 9:102627. doi: 10.1016/j.gim.2026.102627. Online ahead of print.
ABSTRACT
PURPOSE: To systematically evaluate the diagnostic yield of ES and GS for investigating suspected genetic disorders in critically ill neonates and infants.
METHODS: Relevant literature published before December 2024 was retrieved from PubMed, Embase and Web of Science. Eligible cohort studies and case series (≥4 patients) adopting ES/GS as primary diagnostic tools were included. Random-effects proportional meta-analysis, subgroup analysis and meta-regression were performed to synthesize overall diagnostic yield, compare different sequencing modalities, and explore the correlation between diagnostic yield and publication year. This study was registered on PROSPERO (CRD42025631436).
RESULTS: The meta-analysis included 26 ES cohorts (2,205 individuals) and 22 GS cohorts (2,101 individuals). The overall diagnostic yield was 39.4% for ES (95% CI, 32.8%-46.3%) and 39.4% for GS (95% CI, 34.7%-44.1%). Subgroup analyses revealed trends toward higher yields with trio-based sequencing compared to non-trio approaches and with rapid GS compared to rapid ES, although these differences were not statistically significant. The meta-regression did not find a significant change in diagnostic yield over time.
CONCLUSION: The results of this systematic review and meta-analysis indicate the substantial diagnostic utility of both ES and GS in critically ill neonates and infants, providing a molecular diagnosis in nearly two-fifths of cases. These findings support the use of next-generation sequencing to improve diagnostic outcomes in this vulnerable patient population.
PMID:42267533 | DOI:10.1016/j.gim.2026.102627
