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

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

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.

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 GJB2, DUOX2, PRODH, ATP7B, SLC12A3, SLC26A4. 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.

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.