BOSTON, MA - When you have a baby, a nurse or phlebotomist performs a heel stick to take a few drops of blood from your infant and sends it off to a state lab for a battery of tests. Most of the time, you never hear about the results because your child is fortunate enough not to have a rare disease, such as cystic fibrosis or sickle cell disease or any of the dozens of conditions for which most states screen. You, as a parent, may not even remember hearing about newborn screening.
Newborn screening is mandatory in most states, unless parents refuse for religious purposes or other reasons. This practice is generally accepted because screening is only performed for a small number of conditions where measures are available to save the baby's life or mitigate the harms of the condition, if found early enough. However, now that scientists have developed methods for sequencing the entire genome, what would happen if states began incorporating genome sequencing to find out more about baby's health? Or if parents could elect to obtain newborn sequencing from their doctors or from private companies? How would that work? What should parents learn about their baby's genome? What shouldn't they?
To study these questions, through funding from the National Institutes of Health, researchers and doctors across the country have formed a consortium called Newborn Sequencing In Genomic medicine and public HealTh, dubbed NSIGHT, which includes four grants spanning multiple institutions:
- Brigham and Women's Hospital/Boston Children's Hospital and Baylor College of Medicine
- UNC School of Medicine
- UCSF School of Medicine
- UCSD Rady Children's Institute for Genomic Medicine and Children's Mercy Kansas City
This consortium is working with parents - and conducting genomic sequencing on newborns - to develop evidence that may support guidelines for how this new technology could be effectively and appropriately incorporated into newborn screening or the care of newborns.
"Where is the boundary of parental responsibility to learn important health information about their child versus delving too far into genetic information that could take away from that child's ability to make decisions for themselves?" said Jonathan Berg, MD, PhD, associate professor of genetics at the UNC School of Medicine and corresponding author of a paper describing the Consortium, published today in the journal Pediatrics. "This is one of the main bioethics questions of our time. How much should we protect a child's capacity to make decisions about what information to learn, or not to learn, about themselves when they become adults? Some people think withholding such information is an old, quaint, paternalistic notion that is being made obsolete by technology. Yet others believe fervently that it could infringe on the child's autonomy or potentially even harm the child if parents learned or intervened too much."
Examples such as genetic predisposition to childhood cancer, heart disease throughout the lifespan or adult-onset neurodegenerative syndromes quickly generate strong and diverse opinions on these matters. Should parents have a right to learn about these in their infants?
Regardless of what people might think, Berg said, "Technology is forcing this decision-making process on us." The cost of genome sequencing has plummeted in recent years, making personal genetic information and sequencing technology more accessible than ever. Such a drastic change pushes the public health system and the broader medical community to address these issues, and soon. Through the NIH-funded NSIGHT consortium, researchers and doctors are laying the groundwork.
The NSIGHT lead institutions are spearheading the four studies across the country to address three clinical scenarios:
- Diagnostic: using genome sequencing to find the specific genetic causes of congenital anomalies or unexplained illnesses in babies admitted to the hospital early in life.
- Preventative: using genome sequencing to screen healthy newborns for preventable or treatable conditions of childhood that genetic sequencing could detect or help confirm.
- Predictive: using genome sequencing to explore the entire genome of the child, as a resource for health care throughout the course of the child's life.
Critical data gathered from the NSIGHT projects will help to address technical, medical, behavioral and economic questions surrounding newborn sequencing. The projects require patience: some outcomes won't be able to be measured for many years. However, longitudinal follow-up will allow researchers to track patient and parent outcomes post-sequencing and throughout childhood, thereby returning results on a continual basis. Early results have already begun to be seen by some NSIGHT projects - with more on the way.
Ultimately, the cross-sectional data provided by the four NSIGHT projects will aid in the development of best clinical practices and provide guidance on the implementation of sequencing in newborns. Multiple NSIGHT working groups focus their efforts on harmonizing the four projects to ensure the individual data sets are unified for the purpose of answering the consortium's overall questions and goals.
The Boston-based NSIGHT project is called the BabySeq Project and it is co-led by Robert Green, MD, of the Division of Genetics at Brigham and Women's Hospital, Broad Institute and Harvard Medical School and Alan Beggs, PhD, of the Manton Center for Orphan Disease Research at Boston Children's Hospital and Harvard Medical School, both of whom contributed to the Pediatrics paper. In Boston, the BabySeq Project is currently enrolling very ill infants from neonatal intensive care units at the two hospitals, as well as healthy babies from Brigham and Women's. In the sick babies, this clinical trial is asking whether genomic information can add information that will accelerate diagnosis and improve outcomes. In the healthy babies, sequencing is uncovering unanticipated risk information and the project will measure downstream medical, behavioral and economic outcomes that follow.
The BabySeq project has enrolled over 200 families with newborn infants, and earlier this month published a paper in the journal Genetics in Medicine documenting the process by which the project is selecting which genes to return to the families of newborns. Under the leadership of senior author Heidi Rehm, PhD., BabySeq Project investigators evaluated over 1500 genes to generate a list of 954 associated with childhood-onset diseases that met specific criteria for return. The list provides a resource for other groups hoping to return genomic results to children.
"Genome sequencing is a new and still enormously complex process, and oftentimes the results have uncertain implications," said Beggs. "Both BabySeq and the larger NSIGHT Network represent some of the first organized approaches to developing the best practices for determining the right information and best ways to return it to parents and their babies' doctors."
"Simply putting together all the pieces to design these complicated research projects is an ambitious undertaking. But it is essential that we find ways to rigorously measure the clinical utility of new technologies so that we can apply them responsibly, and that is the focus of the BabySeq Project, and of the other NSIGHT projects," said Green.
As genomic technology accelerates and costs decrease, it is easy to imagine a future where newborn babies are empowered with their genetic information from the beginning of their lives. The papers released this week from the NSIGHT Consortium are a start in carefully examining the evidence base that can help decide whether and how this future develops.
The BabySeq Project is funded by the National Institute of Child Health and Development and the National Human Genome Research Institute, both part of the National Institutes of Health.
Aside from the main sites, NSIGHT includes researchers and administrators from the National Institutes of Health (the National Human Genome Research Institute, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Center for Advancing Translational Sciences), RTI International, University of California-Berkeley, American College of Medical Genetics and Genomics, ,University of Illinois-Chicago School of Public Health, California Department of Public Health, Oregon Health & Sciences University, University of Washington, and Benioff Children's Hospital