Can sequencing of newborns’ genomes provide useful medical information beyond what current newborn screening already provides? What results are appropriate to report back to parents? What are the potential risks and harms? How should DNA sequencing information be integrated into patient care?
Four teams from across the country will converge this week (April 8–10) in Kansas City, Mo., to address these questions and share learnings from NIH-funded pilot projects. The four teams, comprising the NIH’s Newborn Sequencing In Genomic medicine and public HealTh (NSIGHT) project, will give updates on their work at the 6th Annual Pediatric Genomics Conference, hosted by Children’s Mercy Kansas City.
“In coming years, genomic sequencing of newborns will likely become a common practice, providing the opportunity for personalized preventive medicine,” says Ingrid Holm, MD, MPH, of the Division of Genetics and Genomics at Boston Children’s Hospital, part of a team that also includes principal investigators Robert Green, MD, MPH, of Brigham and Women’s Hospital and Alan Beggs, PhD, of Boston Children’s Manton Center for Orphan Disease Research, as well Amy McGuire, PhD, JD, of Baylor College of Medicine. “However, in addition to clear benefits for both the infant and their family, the knowledge gained has potential to cause harm, and the long-term impacts on the child and family are not known. We hope our collective work will advance the informed and safe use of genomics in newborns.”
The Boston/Baylor team’s study, Genome Sequence-Based Screening for Childhood Risk and Newborn Illness, also called BabySeq, aims to establish a sound, responsible pipeline for interpreting and reporting sequencing results. It one of four pilots that the National Institute of Child Health and Human Development (NICHD) and the National Human Genome Research Institute (NHGRI) have funded to explore the clinical and ethical issues raised by newborn DNA sequencing.
- The acquisition and analysis of genomic datasets
- Clinical research using DNA sequencing to advance understanding of specific disorders
- Research on newborn sequencing’s ethical, legal and social implications (ELSI)
BabySeq will shortly launch the first randomized trial exploring the clinical outcomes, benefits and risks of DNA sequencing in 480 healthy and sick newborns. Infants will be randomized to conventional newborn screening alone or both conventional screening and genomic sequencing. They’ll then be followed via their medical records to track decisions made based on these results, and their outcomes.
Early results, published in the journal Genomics in Medicine in December, indicate high levels of acceptance and interest among parents of healthy newborns in genomic screening.
The other NSIGHT projects:
- Children’s Mercy Kansas City: Genetic disorders and congenital anomalies are the leading cause of infant mortality. Diagnosis of most genetic diseases in neonatal and pediatric intensive care units (NICU, PICU) does not occur in time to guide acute clinical management. In early results, rapid whole-genome sequencing (STATseq) had a high rate of diagnosis of genetic disorders, and a majority of diagnoses influenced the infants’ NICU or PICU management.
- University of California San Francisco: This pilot project will explore the potential of exome sequencing as a method of newborn screening for disorders, both those currently screened for and others that are not currently screened for, but where screening might offer a benefit. The researchers will examine the value that exome sequencing information adds to existing newborn screening that could help improve care and treatment.
- University of North Carolina Chapel Hill: The NC NEXUS project will utilize whole-exome sequencing (WES) in 200 infants and children with diagnosed conditions as well as 200 healthy newborns. This project, too, will determine the capability of WES to detect conditions currently screened for and its potential to expand screening by developing a “Next Generation Newborn Screen.”
The conference will kick off with a telebriefing for media at 5 p.m. EST, Wednesday, April 8. For more details on the conference and media contacts, visit www.cmh.edu/newborngenomics. The four teams plan to issue a joint white paper after the conclusion of the conference.