Molecular Genetic Screening of Neonatal Intensive Care Units: Hyperbilirubinemia as an Example.

Objective: To explore the clinical value of newborn genomic screening (nGS) for neonatal intensive care units (NICU) infants (taking neonatal hyperbilirubinemia as an example).

Methods: Dried blood spots (DBSs) were collected after 72 hours of birth. The tandem mass spectrometry (TMS) screening and Angel Care genomic screening (GS, based on Targeted next-generation sequencing) were performed at the same time.

Results: Ninety-six hyperbilirubinemia newborns were enrolled in this study and none was identified with inborn errors of metabolism (IEM) by TMS, while 6 infants (6.25%, 6/96) were suspected to have a genetic disorder by Angel Care, including 2 cases of glucose-6-phosphate dehydrogenase deficiency (G6PD), and 1 case of maple syrup urine disease type 1B (MSUD1B), autosomal recessive deafness 1A (DFNB1A), Leber hereditary optic neuropathy (LHON), thyroid dyshormonogenesis 6 (TDH6) each. In addition, 44 infants (45.8%) were detected having at least one variant which conferred a carrier status for a recessive childhood-onset disorder. A total of 33 out of 60 variants (55.0%) reported for carrier status were pathogenic (P), 24 (40.0%) were likely pathogenic (LP), and 3 variants were variant of uncertain significance (VUS). Top six common genes of carrier status were . Two newborns showed abnormalities in elementary screening of TMS, but were confirmed as false positive after recall. Their results of Angel Care did not found abnormality.

Conclusion: Using neonatal hyperbilirubinemia as an example, genome sequencing screening can find more evidence of genetic variation in NICU newborns, and "Angel Care" is an effective method.