Genome Sequence-Based Screening for Childhood Risk
and Newborn Illness
Principal Investigators: Robert C. Green and Alan H. Beggs
Co-Principal Investigators: Peter Park, Heidi Rehm, Pankaj Agrawal, Richard Parad, Ingrid Holm and Amy McGuire
The BabySeq Project: Genomic Sequencing for Childhood Risk and Newborn Illness (U19 HD077671) is a first-of-its-kind randomized clinical trial designed to examine how best to use genomics in clinical pediatric medicine by creating and safely testing methods for integrating sequencing into the care of newborns.
Currently, the risks and benefits of genomic sequencing for newborns are not well understood. All newborns receive “Newborn Screening,” a state-mandated heel stick blood test shortly after birth in order to screen for approximately 30 heritable, treatable conditions such as blood, endocrine, and metabolic disorders. Genomic sequencing has the potential to allow for significantly more extensive screening of disorders that newborns could be at risk for developing during childhood. Earlier diagnosis of these conditions could in turn lead to specific screening, surveillance and treatment options, allowing for more personalized and preventative healthcare.
The extent to which genomic information could benefit or harm newborns and their families remains unclear. Despite this uncertainty, the use of genomic technology is continuing to expand throughout medicine. It is therefore important to study the impact of genomic screening in a safe and controlled manner, before market forces outpace our understanding of the implications of this technology.
The National Institute of Child Health and Human Development (NICHD) and the National Human Genome Research Institute (NHGRI) have committed $25 million over five years to four projects that will investigate the use of genomic sequencing in newborns. In Boston, the BabySeq Project is being led by Dr. Robert C. Green of Brigham and Women’s Hospital (BWH) and Dr. Alan H. Beggs of Boston Children’s Hospital (BCH).
In a pilot study conducted at BWH that helped inform the design of the BabySeq Project, parents of healthy newborns were asked on the BWH post-partum unit how interested they would be in genome screening of their newborn if available through a research study. We also presented a subset of these parents with descriptions of possible results which
could be detected by genome sequencing. These parents were then asked hypothetically which results they would want to receive about their newborn. The vast majority of parents, 82.7 percent, reported being “somewhat” (36 percent), “very” (28 percent), or “extremely” (18 percent) interested in newborn genomic testing.
The BabySeq Project received Institutional Review Board approval in Spring 2015 and enrollment is now underway. The study is enrolling 240 healthy newborns and their families from BWH and 240 newborns and their families from the Neonatal Intensive Care Unit (NICU) at BCH. Each infant is randomized (50:50) to receive genomic sequencing or to a control group. All babies receive state-mandated conventional newborn screening and a family history report, while babies in the sequencing arm also receive a genomic sequencing report. This report contains information about known pathogenic or likely pathogenic (e.g. disease-causing) variants associated with childhood-onset conditions identified in the infant. It may also contain information on “pharmacogenomic” variants, genetic changes that could affect response to certain medications, and the baby’s blood type. Babies in the sequencing arm who have, or develop, health conditions that may have an underlying genetic cause may also receive an “Indication-Based Analysis” that can re-examine the baby’s sequencing information, with a specific focus on genes that have previously been associated with the baby’s specific health condition.
In order to monitor the long-term impact of the genomic information returned to families, parents enrolled in the study are asked to complete four surveys over the course of the first year of enrollment. These surveys ask questions about how parents have been feeling, their family relationships, genetics knowledge, and the perceived utility of the information they receive. We are examining if there are marked differences between the families who receive genomic information and the families who receive standard of care.
We are also enrolling and surveying pediatricians and other doctors involved in the care of enrolled babies to examine how this information may be impacting a child’s medical care.
We hope that this project will provide valuable and unparalleled data to be used to integrate genomic information from newborns into clinical pediatric care.
The BabySeq project is part of a consortium called Newborn Sequencing In Genomic medicine and public HealTh, dubbed NSIGHT. Along with projects at 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, the consortium has been granted $25M over a five year period to gather critical research on newborn sequencing. The NSIGHT consortium investigates 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); and 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 – and ultimately, will aid in the development of best clinical practices and provide guidance on the implementation of sequencing in newborns.
For more information on the BabySeq Project, please email firstname.lastname@example.org.