Transforming NICU care: rapid WES and transcriptomics—validation, social impact, and cost analysis

Abstract

Genetic diseases significantly contribute to morbidity and mortality in neonatal intensive care units (NICUs), with diagnoses often delayed due to clinical complexity. Rapid whole-exome sequencing (rWES) and transcriptomic analysis (RNA-seq) may improve diagnostic rates and clinical outcomes. Prospective study of neonates admitted to NICUs with suspected genetic diseases (n = 34) who underwent rWES, followed by RNA-seq applied in cases in which rWES failed to establish diagnosis. The primary outcome was the diagnostic rate. Secondary outcomes included time to diagnosis, clinical utility, parental stress, and cost-effectiveness. rWES achieved a 41% diagnostic rate with a mean turnaround time of 8.57 ± 2.62 days. RNA-seq increased the diagnostic yield by 6%, resulting in a total diagnostic rate of 47%. The use of rWES reduced unnecessary procedures by 15% and shortened hospital stays by 25% (p < 0.01). Cost-effectiveness analysis indicated that rWES was economically advantageous, with an ICER of < €9000. Relative to pre-diagnosis levels, parental anxiety decreased by 30% in cases in which diagnosis was achieved but increased by 15% in cases in which no diagnosis was established (p < 0.05). Conclusion: Implementing rWES in NICUs improves care for critically ill neonates by providing timely, accurate diagnosis, reducing healthcare costs, and alleviating parental anxiety. RNA-seq further enhances diagnostic accuracy.