As genomic sequencing becomes increasingly commonplace in the clinic, questions remain about its use and role among newborns. Can sequencing provide actionable insights? How common is it to find something relevant to a child's future health? What benefits or consequences will sequencing have for families?.

The BabySeq Project, a joint endeavor led by investigators at Brigham and Women's Hospital and Boston Children's Hospital, with collaborators at the Baylor College of Medicine, is revealing the answers to these questions and more. In a paper published in the American Journal of Human Genetics, the research team reports that genomic sequencing can identify risk for a wide range of disorders that may not be detected otherwise.

New borns

Importantly, early knowledge about several of these conditions can lead to surveillance and interventions that could improve health outcomes for newborns and their families. "The BabySeq Project is the first randomized trial of sequencing in newborns and the first study to fully examine the wealth of unanticipated genetic risk information in children," said Robert Green, MD, MPH, co-director of the study at the Brigham and a professor at Harvard Medical School.

"We were stunned by the number of babies with unanticipated genetic findings that could lead to disease prevention in the future." The BabySeq Project enrolled healthy newborns from the Brigham's well-baby nursery and ill newborns from BCH, the Brigham and Massachusetts General Hospital's neonatal and pediatric intensive care units.

Family histories were collected for all enrolled participants. Half of the families from each group were randomized to receive standard care, including "heel prick" newborn screening which tests for about 30 genetic conditions, and genetic counseling based on family history; the other half received whole exome sequencing in addition to standard care and genetic counseling. Sequencing results were disclosed to families during the genetic counseling session.

The team monitored health outcomes and collected medical, behavioral and economic data at the time of disclosure, three months later and ten months later to measure the impact of genomic sequencing on the infant's clinical care, parent and clinician behaviors, and economic outcomes. A total of 159 newborns (128 healthy newborns and 31 ill newborns) were randomized to receive genomic sequencing.

Of those, 15 (9.4 %) were found to have a genetic variant for which there was substantial evidence of increased risk of a disorder that presents or is clinically manageable during childhood or an option in a gene for which there was moderate evidence of risk but for which an intervention during childhood might prevent devastating outcomes later in life.

The team found variants associated with several heart conditions, including six newborns with variants associated with dilated or hypertrophic cardiomyopathy and another newborn with an option associated with supravalvular aortic stenosis. These conditions can be monitored over time, and families have been referred to cardiac specialists. Another newborn was found to have a risk variant for biotinidase deficiency.

Further testing determined that the infant had partial biotinidase deficiency, a condition that can cause skin rash, hair loss, and seizures. The child's diet is now being supplemented with biotin, which is expected to prevent any disease manifestations.