Sequencing Newborns:A Call for Nuanced Use of Genomic Technologies

Abstract

Many scientists and doctors hope that affordable genome sequencing will lead to more personalized medical care and improve public health in ways that will benefit children, families, and society more broadly. One hope in particular is that all newborns could be sequenced at birth, thereby setting the stage for a lifetime of medical care and self-directed preventive actions tailored to each child's genome. Indeed, commentators often suggest that universal genome sequencing is inevitable. Such optimism can come with the presumption that discussing the potential limits, cost, and downsides of widespread application of genomic technologies is pointless, excessively pessimistic, or overly cautious. We disagree. Given the pragmatic challenges associated with determining what sequencing data mean for the health of individuals, the economic costs associated with interpreting and acting on such data, and the psychosocial costs of predicting one's own or one's child's future life plans based on uncertain testing results, we think this hope and optimism deserve to be tempered. In the analysis that follows, we distinguish between two reasons for using sequencing: to diagnose individual infants who have been identified as sick and to screen populations of infants who appear to be healthy. We also distinguish among three contexts in which sequencing for either diagnosis or screening could be deployed: in clinical medicine, in public health programs, and as a direct-to-consumer service. Each of these contexts comes with different professional norms, policy considerations, and public expectations. Finally, we distinguish between two main types of genome sequencing: targeted sequencing, where only specific genes are sequenced or analyzed, and whole-exome or whole-genome sequencing, where all the DNA or all the coding segments of all genes are sequenced and analyzed. In a symptomatic newborn, targeted or genome-wide sequencing can help guide other tests for diagnosis or for specific treatment that is urgently needed. Clinicians use the infant's symptoms (or phenotype) to interrogate the sequencing data. These same complexities and uncertainties, however, limit the usefulness of genome-wide sequencing as a population screening tool. While we recognize considerable benefit in using targeted sequencing to screen for or detect specific conditions that meet the criteria for inclusion in newborn screening panels, use of genome-wide sequencing as a sole screening tool for newborns is at best premature. We conclude that sequencing technology can be beneficially used in newborns when that use is nuanced and attentive to context.

Genetic counselors' perceptions of uncertainty in pretest counseling for genomic sequencing: A qualitative study

“…Pretest genetic counseling, which includes but is not limited to the informed consent process has been emphasized as an essential component to prepare patients and family for potential genomic information and its implications (Babrow, Kasch, & Ford, 1998;Doyle et al, 2016;Skirton & Bylund, 2010;Volk, Conboy, Wical, Patterson, & Kirmani, 2015). The critical nature of this process is emphasized by the growing body of literature calling for responsible and prospective reflection of the potential benefits and harms of genomic sequencing in light of its expanding uptake in medicine (Allyse, Sayres, King, Norton, & Cho, 2012;Johnston et al, 2018;ACMG, 2012;Green et al, 2013).…”

Who should access germline genome sequencing? A mixed methods study of patient views

“…Claims in support of newborn GS, therefore, need to show that overall benefits outweigh the harms. 15,16 Our participants' support for testing in newborns and children may also reflect familiarity with the widely-accepted and routine practice of biochemical newborn screening in Australia, which screens for rare but serious conditions including phenylketonuria, hypothyroidism and cystic fibrosis.…”

Qualitative Research on Expanded Prenatal and Newborn Screening: Robust but Marginalized

“…Growth in both prenatal and newborn testing, impressive though it may be, is predicted by many to be small in comparison to what we might expect to see as genomic medicine advances. The cost of sequencing an individual’s genome is continually decreasing, and many believe that a future in which all newborns are routinely sequenced at or before birth is both inevitable and desirable …”

“…The cost of sequencing an individual's genome is continually decreasing, and many believe that a future in which all newborns are routinely sequenced at or before birth is both inevitable and desirable. 12 It is against this historical backdrop, characterized by broadly employing whatever screening capacities technological advances make possible, 13 that I explore insights from interpretive qualitative research that have consistently signaled that screening expansion is changing people's lives in significant and unintended ways. The evidence generated by this work is not easily adapted for cost-benefit analyses or aggregated into metasyntheses that mimic evidence review as practiced in the quantitative paradigm.…”