Genomic sequencing in newborn to improve healthcare: pilot projects funded by NIH!

As NGS technology became cheaper and more robust in the next few years and our knowledge about genotype-phenotype associations increase, the idea of performing whole genome sequencing as a standard test on newborns may became an actual strategy in healthcare.

The genomes of infants may be able to be sequenced shortly after birth and allow parents to know what diseases or conditions their child may be affected by or have a propensity for developing, giving them the chance to possibly head them off or start on early treatments.

To test this approach, the US National Institutes of Health has awarded $5 million in research grants to four pilot programs to study newborn screening. The research programs aim to develop the science and technology ad well as to investigate the ethical issues related to such screening.

This pilot project, covered also by The New York Times, is the first effort to asses impact of whole genome screening on the quality of life and on our ability to provide better healthcare. 

Genomic sequencing may reveal many problems that could be treated early in a child’s life, avoiding the diagnostic odyssey that parents can endure when medical problems emerge later, said Dr. Cynthia Powell, winner of one of the research grants.

However, the role of each and every variant and how to interpret their contribution to disease risk is not yet fully understood and many questions remain on which variants to report and if and how genomic findings translate into improved therapies or life quality. This matter will also be addressed in the funded studies.

“Many changes in the DNA sequence aren't disease-causing,” said Dr. Robert Nussbaum, chief of the genomic medicine division at the School of Medicine of the University of California, San Francisco, and leader of one of the pilot grants. “We aren't very good yet at distinguishing which are and which aren’t.”

“You will get dozens of findings per child that you won’t be able to adequately interpret,” said , Dr. Jeffrey Botkin, a professor of pediatrics and chief of medical ethics at the University of Utah. The ethical issues of sequencing are sharply different when it is applied to children. Adults can decide which test information they want to receive, but children won’t usually have that option. Their parents will decide and children will get information that he will rather prefer to ignore when he became adult.

"We are not ready now to deploy whole genome sequencing on a large scale," said Eric Green, the director of the National Human Genome Research Institute, that promote the research program, "but it would be irresponsible not to study the problem."
"We are doing these pilot studies so that when the cost of genomic sequencing comes down, we can answer the question, 'Should we do it?' " he adds.

Here are the four pilot project funded by the NIH, as reported in the official news:

• Brigham and Women's Hospital and Boston Children's Hospital, Boston
  Principal Investigators: Robert Green, M.D., and Alan Beggs, Ph.D.
  
  This research project will accelerate the use of genomics in pediatric medicine by creating and safely testing new methods for using information obtained from genomic sequencing in the care of newborns. It will test a new approach to newborn screening, in which genomic data are available as a resource for parents and doctors throughout infancy and childhood to inform health care.  A genetic counselor will provide the genomic sequencing information and newborn screening results to the families.  Parents will then be asked about the impact of receiving genomic sequencing results and if the information was useful to them.  Researchers will try to determine if the parents respond to receiving the genomic sequencing results differently if their newborns are sick and if they respond differently to receiving genomic sequencing results as compared to current newborn screening results. Investigators will also develop a process for reporting results of genomic sequencing to the newborns' doctors and investigate how they act on these results.
   
• Children's Mercy Hospital - Kansas City, Mo.
  Principal Investigator: Stephen Kingsmore, M.D.
  
  Many newborns require care in a neonatal intensive care unit (NICU), and this group of newborns has a high rate of disability and death. Given the severity of illness, these newborns may have the most to gain from fast genetic diagnosis through the use of genomic sequencing. The researchers will examine the benefits and risks of using rapid genomic sequencing technology in this NICU population. They also aim to reduce the turnaround time for conducting and receiving genomic sequencing results to 50 hours, which is comparable to other newborn screening tests. The researchers will test if their methods increase the number of diagnoses or decrease the time it takes to reach a diagnosis in NICU newborns. They will also study if genomic sequencing changes the clinical care of newborns in the NICU.  Additionally, the investigators are interested in doctor and parent perspectives and will try to determine if parents' perception of the benefits and risks associated with the results of sequencing change over time.
   
• University of California, San Francisco 
  Principal Investigator: Robert Nussbaum, M.D.
  
  This pilot project will explore the potential of exome sequencing as a method of newborn screening for disorders currently screened for and others that are not currently screened for, but where newborns may benefit from screening. The researchers will examine the value of additional information that exome sequencing provides to existing newborn screening that may lead to improved care and treatment. Additionally, the researchers will explore parents' interest in receiving information beyond that typically available from newborn screening tests. The research team also intends to develop a participant protection framework for conducting genomic sequencing during infancy and will explore legal issues related to using genome analysis in newborn screening programs. Together, these studies have the potential to provide public health benefit for newborns and research-based information for policy makers.
   
• University of North Carolina at Chapel Hill 
  Principal Investigators: Cynthia Powell, M.D., M.S., and Jonathan Berg, M.D., Ph.D.
  
  In this pilot project, researchers will identify, confront and overcome the challenges that must be met in order to implement genomic sequencing technology to a diverse newborn population. The researchers will sequence the exomes of healthy infants and infants with known conditions such as phenylketonuria, cystic fibrosis or other disorders involving metabolism. Their goal is to help identify the best ways to return results to doctors and parents. The investigators will explore the ethical, legal and social issues involved in helping doctors and parents make informed decisions, and develop best practices for returning results to parents after testing. The researchers will also develop a tool to help parents understand what the results mean and examine extra challenges that doctors may face as this new technology is used. This study will place a special emphasis on including multicultural families.