Martín López-Pardo Beatriz, Barbosa-Gouveia Sofía, Vázquez-Mosquera María-Eugenia, Reyes Francisco, Falcão Reis Claudia, Laranjeira Francisco, Sánchez-Tamayo Tomas, Sánchez-Pintos Paula, Fernández-Feijoo Cristina Durán, Pérez-Muñuzuri Alejandro, Couce María-Luz
Unit of Diagnosis and Treatment of Congenital Metabolic Diseases, Department of Neonatology, Santiago de Compostela University Clinical Hospital, Choupana Street, 15704, Santiago de Compostela, Spain.
IDIS-Health Research Institute of Santiago de Compostela, Santiago de Compostela University Clinical Hospital, Choupana Street, 15704, Santiago de Compostela, Spain.
Eur J Pediatr. 2025 Jun 27;184(7):453. doi: 10.1007/s00431-025-06225-2.
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.
遗传疾病是新生儿重症监护病房（NICU）发病和死亡的重要原因，由于临床情况复杂，诊断往往会延迟。快速全外显子测序（rWES）和转录组分析（RNA-seq）可能会提高诊断率和临床疗效。对入住NICU且疑似患有遗传疾病的新生儿（n = 34）进行前瞻性研究，这些新生儿接受了rWES检测，对于rWES未能确诊的病例，随后应用RNA-seq检测。主要结局是诊断率。次要结局包括诊断时间、临床实用性、家长压力和成本效益。rWES的诊断率为41%，平均周转时间为8.57±2.62天。RNA-seq使诊断率提高了6%，总诊断率达到47%。使用rWES减少了15%的不必要检查，并使住院时间缩短了25%（p<0.01）。成本效益分析表明，rWES在经济上具有优势，增量成本效果比<9000欧元。与诊断前水平相比，确诊病例的家长焦虑下降了30%，但未确诊病例的家长焦虑增加了15%（p<0.05）。结论：在NICU实施rWES可通过提供及时、准确的诊断、降低医疗成本和减轻家长焦虑来改善对危重新生儿的护理。RNA-seq进一步提高了诊断准确性。
