When you have a baby, a nurse or a 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 to not 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 or other reasons. Screening 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 such conditions, 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? 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 (NIH), researchers and doctors across the country have formed a consortium called NSIGHT, which includes four NIH grants spanning multiple institutions:
- UNC School of Medicine
- UCSF School of Medicine
- Brigham and Women’s Hospital/ Boston Children’s Hospital and Baylor College of Medicine
- UCSD Rady Children’s Institute for Genomic Medicine and Children’s Mercy Kansas City
This consortium will work with parents and conduct 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 about the consortium’s work, 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 this concern is an old, quaint notion that is being made obsolete by technology. And some people believe fervently that it could infringe on the child’s autonomy or potentially even harm the child if parents learned or intervened too much.”
One clear example is Huntington’s disease. Is it the right of the parent to know that their child harbors the genetic lesion that underpins this terrible disease, even though manifestations are unlikely to develop until adulthood? What about an untreatable neurodegenerative disease that will present during childhood? What if early intervention might help, but the disease might not present until the child is an adult?
The lead NSIGHT 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 neonatal intensive care units.
• Preventative: using genome sequencing to screen healthy newborns for preventable or treatable conditions 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.
Currently, NISIGHT doctors and researchers are consulting with parents and soon-to-be parents to learn about their concerns and their personal decision-making processes regarding genome sequencing for various purposes, including finding health information that could be clinically useful immediately.
At UNC, the principal investigator of the NIH-funded NC NEXUS project – part of the NSIGHT consortium – is Cynthia Powell, MD, professor of pediatrics and genetics, along with Berg, the co-principal investigator.
“Current newborn screening saves lives,” Powell said. “We want to find out if expanding screening methods to include genome sequencing would save more lives and what such screening might look like.”
UNC researchers are studying two groups of patients: those already diagnosed with conditions detectable by newborn screening and a cohort of healthy newborns. Parents will use an electronic decision aid, created by RTI International in collaboration with UNC clinicians and researchers, to help them decide whether to have their baby undergo sequencing. If they do, parents will receive results about a few hundred genes related to conditions that are considered “medically actionable” in childhood. Because these are all rare conditions, most babies will have normal screening results. Those in the group already diagnosed with a condition will have additional analysis of genes related to their condition, in order to assess how well sequencing performs at detecting those conditions.
All of the participants will be further randomized into two groups. One group is finished once they give researchers feedback on the genome sequence decision-making tool and their reactions to learning their sequencing results. A second group of parents is presented with the decision of whether to learn about any of three additional categories of genetic information – ways in which their child’s genetic information could be used immediately or in the future.
“We want to know why parents think the way they do,” Berg said. “If a parent is against sequencing, why? If they are for it, what are their reasons for wanting their child’s genome sequenced? Why might they want one category of genomic information but not another? What are the benefits and harms?”
For the healthy newborn cohort, Powell and colleagues are approaching parents well before their babies are born, and even then, the researchers say it’s difficult to find the right time to approach parents with these weighty ideas and possibilities.
“We’re learning when the best time is to approach parents,” Berg said. “Clearly, immediately after birth we can’t just say to a new mom and dad, ‘we’d like to talk to you for a few hours about your thoughts on sequencing your child’s entire genome.’
“We’re learning what kinds of decision aids and other resources parents need, such as genetic counseling. We’re wrestling with how to implement this in practice when we already have a shortage of genetic counselors in the United States. We can’t have every single couple sit down with a genetic counselor, but we could have them go through an online decision aid.”
Berg, who is also a member of the UNC Lineberger Comprehensive Cancer Center, said the consortium is finding that while many parents simply aren’t interested in genomic sequencing for their newborns, there’s a subset of parents who want to dive into the genetic information. “Perhaps it would be appropriate to focus our genetic counseling resources on them,” he said.
“The bottom line is this,” Berg added. “We hope that the information we get from these studies will help us make recommendations for how to best roll out some form of newborn genomic screening in the future.”