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.
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?
‘Clinical geneticists are part of a national consortium of researchers studying the pros and cons of genome sequencing for newborn health.’
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
- 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, associate
professor of genetics at the UNC School of Medicine and corresponding
author of a paper describing the Consortium, published today in the
"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, of the Division of Genetics at Brigham
and Women's Hospital, Broad Institute and Harvard Medical School and
Alan Beggs, 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, 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
"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
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.