The ability to know a child’s entire genome sequence at birth will soon be within reach. The unanswered question is what it will mean for newborn screening programs, which collect dried blood specimens from nearly every child born in the United States. We can look to past and present experiences in newborn screening for preliminary answers.
First, the relationship between technological innovation and newborn screening expansion has revealed a pattern of adoption that favors multiplex testing, as WGS would involve. Therefore, to the extent that genome sequence data can be used for screening and confirmation of numerous conditions, adoption of multiplex genetic testing (e.g., conducting multiple genetic tests simultaneously) may be viewed as financially and technically advantageous. The story line is likely to unfold similarly to that of MS/MS, where the technology garnered support among the newborn screening laboratory stakeholders and the opportunity to screen for previously unscreenable disorders galvanized disease-specific advocacy groups. The increasingly common pattern of industry-advocacy partnerships is likely to augment the power and influence of these groups. It should be recognized that genetic analysis already plays a key role in the newborn screening algorithm for cystic fibrosis. In most states, screening for cystic fibrosis involves an enzyme-level analysis for immunoreactive trypsinogen followed by a reflexive mutational analysis of the CFTR gene using the dried blood spot. In some states, infants who have elevated immunoreactive trypsinogen levels but no CFTR mutations are considered to have screened negative for cystic fibrosis and require no further testing. As use of these types of reflexive genetic analyses grows, it is conceivable that the incremental cost of sequencing the genome may become lower than the cost of conducting separate mutational analyses for different disorders. However, WGS is unlikely to replace all of the current newborn screening tests. There are still instances in which biochemical tests perform better than genetic analyses in screening and diagnosing disorders. For example, direct measurement of phenylalanine level is a simpler and more accurate method to detect infants with PKU than DNA-based testing. That being said, genomic analyses are still likely to become an increasingly useful adjunct to newborn screening.
Nonetheless, the potential integration of WGS into newborn screening is likely to exacerbate the existing newborn screening challenges discussed above. First, the states hold the ultimate authority in deciding which disorders to screen for and how. Historically, SACHDNC has not provided recommendations on what laboratory standards states should use in screening for disorders that it recommends in the RUSP. As was clearly demonstrated by the MS/MS expansion, SACHDNC focuses its recommendations on disorders and not technology—even though the two may be closely linked (3
Even if states choose to adopt WGS simply because it makes technical and financial sense, they will grapple with how to handle the excess information that is generated. To not filter results from WGS may leave clinicians and families drowning in genomic data but with little useful information. This will only exacerbate the challenges related to indeterminate results, education, and communication that already exist for parents and providers. Yet filtering WGS data so that only information on disorders in the RUSP is included may also raise public concern, not only because these are genomic data but also because the data were obtained within the context of a mandatory public health program. The public will undoubtedly want to know what happens to the filtered data. It seems that prior to the integration of WGS, it will be critical to educate and engage the public in the broader decision-making process. The challenge lies in finding ways to successfully and productively engage the public in a meaningful discussion.
In summary, it is likely that newborn screening will imminently confront the prospect of integrating WGS. Whether WGS will transform the current child welfare ethical framework underpinning newborn screening or be adopted as a technological enhancement for screening and diagnosis of disorders within that framework remains to be seen. Regardless, the existing ethical challenges facing newborn screening are likely to be exacerbated by the use of WGS. As newborn screening programs enter the genomics era, they must focus on addressing issues of equity, access, and education that have persisted since the system’s inception 50 years ago.