BabySeq2

Currently, all babies born in the U.S. are screened for up to 35 health conditions on the Recommended Uniform Screening Panel (RUSP).

Thousands of other conditions could be screened at the same time using genome sequencing.

Enter BabySeq, an NIH-funded study led by investigators at Harvard Medical School, Brigham and Women’s Hospital and Boston Children’s Hospital, along with collaborators at Baylor College of Medicine.

There have been two phases: BabySeq 1 and BabySeq 2. Corewell Health is part of BabySeq 2, and the site co-principal investigator is Ramin Homayouni, Ph.D., professor in the OUWB Department of Foundational Medical Studies and founding director of the school’s Population Health Informatics program.

How it works is relatively simple: a parent(s) of a healthy newborn enrolls in the program; a family history is collected; and half of the babies are randomly selected for full genome sequencing.

Every participant will receive genetic counseling based on their family history assessment.

For participants in the sequencing arm of the study, a small amount of blood is collected from the baby’s heel and shipped for sequencing by the Partner’s Healthcare Laboratory for Molecular Medicine, which is a CLIA-certified diagnostic laboratory founded by Brigham and Women’s Hospital and Massachusetts General Hospital.

Only gene variants that are clearly linked to childhood onset diseases are reported back to the participants and their health care providers. Working together with genetic counselors and the research team, the providers will be able to develop a personalized care plan for the babies and their families.

For example, there are 270 disorders that can be treated with supplements or diet, 328 diseases have specific medications available, 175 diseases can be cured with stem cell or organ transplants, and 36 disorders can be managed with specific procedures.

Importantly, notes Homayouni, having diagnostic-grade genome sequencing done once will continue to provide insights for the individual in the future, as more genetic risk variants are being discovered by scientists each day.

Results from BabySeq 1 were featured in a paper published early last year in the American Journal of Human Genetics.

A total of 159 newborns received genomic sequencing. Of those, 9.4% were found to have a genetic variant for which there was strong or moderate evidence of increased risk of a disorder that presents or is clinically manageable during childhood.

"The results of this study indicate that conducting thorough genetic sequencing of newborns has the potential to significantly improve health outcomes for infants and their families," co-author Alan Beggs, BabySeq co-leader and director of Boston Children's Hospital's Manton Center for Orphan Disease Research, said in a statement.

One identified limitation of the study, however, was that it wasn’t diverse enough.

That’s why for BabySeq 2, collaborators like the Beaumont Research Institute at Corewell Health were added late last spring. Others included pediatric practices affiliated with the University of Alabama Birmingham, Icahn School of Medicine at Mount Sinai, and Children’s Hospital of Pennsylvania.

The goal is to enroll a diverse group of 500 newborns from across the participating sites.

Homayouni says having a more diverse population involved in the study will help answer important questions: how does genetic sequencing impact the infants, their families, and medical care providers; and what does it mean for health care costs?

Perhaps the biggest question: Does the evidence support routine use of genomics in healthy newborns?

“If we were to sequence every individual from now on as part of our normal clinical care, would there be value?” he asks.