How can we bring genomics into newborns and childhood care? This is a complex question that Robert Green, Professor of Medicine & Director of Genomes2People Research Program, Brigham and Women’s Hospital, unpacked.
Green advocated for the implementation of preventative genomics and its cost-effectiveness in healthy adults and newborns. The Genomes2People programme carefully considers the benefits, risks, and costs of applying genomics in a variety of ways. The team at Genomes2People has led pioneering research on genetic information and developed policies on returning these findings through multiple projects and collaborations. Green explained that his team had to weigh up the potential benefits and harms when sequencing newborns and children.
The BabySeq project, launched around 2012, is the world's first to sequence healthy newborns, aiming to identify treatable genetic conditions early on. The first baby was enrolled in the project on May 22nd 2015. While there is a heel stick test that tests for 30 – 60 conditions, mainly metabolic conditions, this is a rather unconsented test. Furthermore, given that cell and gene therapies are moving at a rapid pace so there is a demand to screen for more genetic conditions.
From a practical standpoint, the team initially struggled to determine which genes should be screened, so they began by rolling out smaller panels with between 200 and 400 gene panels. The BabySeq project ended up examining 4,299 genes, which were selected based on disease validity, variant pathogenicity, and age of onset. Furthermore, determining which variants to report was also challenging since some variants may be pathogenic while others may be benign. Additionally, some variants may have an unknown significance if the relationship between the gene and disease is still being hypothesised.
Regarding the potential harms, the scientific community has expressed concerns on how newborn sequencing could lead to catastrophic distress, parent-child bonding issues, disruption over medicalisation, overspending in the healthcare system, and actual harm to the baby. However, follow-up research uses a randomised clinical trial format to compare outcomes between sequenced and non-sequenced groups. The results showed that those who volunteered for this project did not experience catastrophic distress.
Green added: “Now that's not to say that we should be cavalier about this information, but the concept of catastrophic psychological distress has been grossly overestimated and should not be a barrier to font families who want this.” While this sequencing resulted in more economic spending, Green commented that these extra costs were not extortionate.
The project revealed highly actionable results, with many identified conditions being manageable or treatable. 11% of the sequenced newborns carried medically meaningful genetic variants. This unique and life-changing project has inspired the formation of the International Consortium on Newborn Sequencing (Icons), which aims to expand genome sequencing in newborns globally.
