Work

Integrating newborn genetic screening with traditional screening to improve newborn screening

Year: 2025

Type: article

Abstract: OBJECTIVE: Traditional newborn screening (tNBS) for inborn errors of metabolism (IEMs) and deafness has limitations, including the detection of few genetic disorders and variants, high false-positive rates, and long turnaround times. This study aimed to explore the clinical validity of newborn genetic screening (NBGS) in newborns screened for IEMs and deafness. METHODS: We retrospectively enrolled 223 cases screened for IEMs using tandem mass spectrometry-next-generation sequencing (MS/MS-NGS), including 55 study-defined positive, 68 study-defined suspected positive, and 100 negative cases. Additionally, 196 cases screened for deafness were enrolled, including 96 variant-positive and 100 negative cases. Dried blood spot samples (DBSs) from newborns were used for NBGS. RESULTS: For IEM, NBGS detected 34 positives in 55 study-defined positive cases with a sensitivity of 61.8% (34/55), no variants were detected in 21 cases. Four additional positive cases were identified, including one at risk of glucose-6-phosphate dehydrogenase deficiency and three at risk of deafness. The turnaround time was significantly different between the two methods: 13 days for NBGS versus 35 days for MS/MS-NGS. For deafness, the consistency of the positive results between the two methods was 96.9% (93/96). Unexpectedly, three mitochondrial gene (MT-RNR1) heteroplasmy variants (m.1555A > G and m.7445A > G) were not detected by NBGS. We also detected nine variants in the 100 negative cases, including seven variants in GJB2 (c.109G > A), one in GJB3 (c.547G > A), and one in MYO15A (c.10250_10252delCCT), for a 9% (9/100) detection rate by NBGS. CONCLUSION: As an emerging screening method for newborns, NBGS offers the potential to detect a broader spectrum of pathogenic gene variants, reduce false-positive rates, and shorten the diagnostic cycle. However, current NBGS technology has limitations and cannot fully supplant traditional detection methods. Therefore, integrating both approaches can become a critical strategy for enhancing the accuracy and efficiency of newborn screening.

Source: The Journal of Maternal-Fetal & Neonatal Medicine

DOI: 10.1080/14767058.2025.2583588