Putting genome-wide sequencing in neonates into perspective

Area of Science:

• Genetics
• Neonatal Medicine
• Diagnostic Yield

Background:

• Rapid exome/genome sequencing (rES/GS) shows promise in neonatal intensive care unit (NICU) settings, with reported yields up to 57% as a standalone test.
• The incremental diagnostic value of rES/GS over existing methods in NICU patients remains unclear.

Purpose of the Study:

• To quantify the additional diagnostic yield of rapid exome sequencing (rES) compared to standard genetic workups in NICU patients.
• To evaluate the impact of genetic diagnoses on clinical management in NICU settings.

Main Methods:

• Retrospective analysis of 132 genetic NICU consultations over a 2-year period.
• Comparison of diagnostic yields between standard genetic workups and exome sequencing (ES).

Main Results:

• Standard genetic workups successfully diagnosed 84.4% (27/32) of cases, with most diagnoses (65.6%) made within 16 days.
• The diagnostic yield of exome sequencing (ES) was 17.2% (5/29) in this cohort.
• Genetic diagnoses directly influenced clinical management in 90.6% (29/32) of patients.

Conclusions:

• Exome sequencing has a role in NICU diagnostics, but its high cost and the effectiveness of alternative strategies warrant careful consideration.
• Clinical genetic consultation should be prioritized as the initial diagnostic step in NICU patients due to its high yield and cost-effectiveness.