Interpretation of Genomic Sequencing Results in Healthy and Ill Newborns: Results from the BabySeq Project

Am J Hum Genet. 2019 Jan 3;104(1):76-93. doi: 10.1016/j.ajhg.2018.11.016.


Genomic sequencing provides many opportunities in newborn clinical care, but the challenges of interpreting and reporting newborn genomic sequencing (nGS) results need to be addressed for its broader and effective application. The BabySeq Project is a pilot randomized clinical trial that explores the medical, behavioral, and economic impacts of nGS in well newborns and those admitted to a neonatal intensive care unit (NICU). Here we present childhood-onset and actionable adult-onset disease risk, carrier status, and pharmacogenomics findings from nGS of 159 newborns in the BabySeq Project. nGS revealed a risk of childhood-onset disease in 15/159 (9.4%) newborns; none of the disease risks were anticipated based on the infants' known clinical or family histories. nGS also revealed actionable adult-onset disease risk in 3/85 (3.5%) newborns whose parents consented to receive this information. Carrier status for recessive diseases and pharmacogenomics variants were reported in 88% and 5% of newborns, respectively. Additional indication-based analyses were performed in 29/32 (91%) NICU newborns and 6/127 (5%) healthy newborns who later had presentations that prompted a diagnostic analysis. No variants that sufficiently explained the reason for the indications were identified; however, suspicious but uncertain results were reported in five newborns. Testing parental samples contributed to the interpretation and reporting of results in 13/159 (8%) newborns. Our results suggest that nGS can effectively detect risk and carrier status for a wide range of disorders that are not detectable by current newborn screening assays or predicted based on the infant's known clinical or family history, and the interpretation of results can substantially benefit from parental testing.

Keywords: genomic sequencing; newborn; newborn screening; newborn sequencing; whole-exome sequencing.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Age of Onset
  • Disease / genetics*
  • Exome Sequencing
  • Female
  • Genetic Predisposition to Disease / genetics
  • Genetic Testing*
  • Genetic Variation / genetics
  • Genome, Human / genetics*
  • Genomics*
  • Health*
  • Heterozygote
  • Humans
  • Infant, Newborn
  • Male
  • Pharmacogenetics
  • Racial Groups / genetics
  • Sequence Analysis, DNA*