Genome Sequencing Is Saving Lives in the NICU

Genome sequencing for newborns was a hot topic at last week’s annual meeting of the American Society of Human Genetics. It’s being used for a specific purpose: diagnosing critically ill infants when there is no obvious explanation for what’s wrong. Throughout this busy conference, several scientists gave presentations about how genome sequencing is making a difference for newborns, often through neonatal infant care units (NICUs). Those talks and posters underscore the growing trend of turning to comprehensive DNA data when conventional tests or diagnostic approaches can’t provide answers — or can’t do so fast enough to help.

Analyzing entire genomes has led to enormous progress in diagnosing genetic diseases and disorders, especially the rare ones that might normally take years to identify. For very ill newborns, this approach can be a literal lifesaver. The alternative is running a battery of tests, most of them purpose-built to detect the cause of a single disease. Each test requires some kind of biological sample, so physicians often have to prioritize tests because there isn’t enough sample available to run them all.

Genome sequencing takes that approach and stands it on its head. Instead of testing for one thing at a time, why not analyze all of the DNA in one shot, and then sift through the data to see what’s there? It can’t answer every clinical question — not by a long shot — but it has, in scientists’ parlance, “increased the diagnostic yield” compared to standard methods. In plain English: it solves cases that conventional tests can’t. In some situations, physicians will order trio sequencing, which involves scanning the DNA of both biological parents in addition to the baby. Having the parents’ data makes it easier to speed through the millions of variants present in any individual genome, highlighting differences or novel variants that might be related to the baby’s condition.

It’s not just that genome sequencing is being used for more babies; much of the progress in achieving these critical diagnoses stems from scientists who are constantly working to improve the process. In recent years, the time it takes to sequence a genome has been slashed from days to a matter of hours. In one example from Boston Children’s Hospital presented at the ASHG conference, scientists reported sequencing and analyzing the genomes of NICU babies in just four hours.

For critically ill newborns, that kind of speed matters. Early detection of a disease or disorder enables early intervention. In some cases, rapid answers can mean the difference between living a relatively normal life and having a drastically shortened lifespan or severely reduced quality of life. When gene therapy is available and administered early enough — such as for spinal muscular atrophy, for instance — babies with potentially lethal conditions might be fully cured.

Meanwhile, costs have been coming down as well. Depending on the technology used, a full human genome sequence might only cost a few hundred dollars. (Though these ultra rapid sequencing efforts cost more than that; they typically use more advanced technologies and require quite a bit of analytical expertise to interpret data that fast.) Even at a few thousand dollars, a human genome sequence for critically ill infants is a bargain compared to the total cost of all the standalone tests that would otherwise have to be run.

All of these improvements are paying off in access to genome sequencing capabilities. A survey conducted by researchers at Boston Children’s Hospital and reported at ASHG by Monica Wojcik, a neonatologist and geneticist, found that 69% of NICUs designed for the very sickest babies are offering some form of genome sequencing for their patients. Wojcik also suggested that the availability of this DNA analysis will advance diagnostic equity — the goal of bringing answers to more families regardless of their economic status or insurance coverage.

Without a doubt, this is great news for families with genetic diseases and disorders. But we also have to keep an eye on the ethics of generating all of this data for patients too young to consent to it. Genome data doesn’t just reveal the cause of a specific disease; it can also spot susceptibilities to diseases that might not kick in until much later in life, such as Huntington’s or Alzheimer’s. At this point, hospital teams generating the data for newborns are reporting only the pathogenic cause of disease for the infant, but what happens with the rest of that data? Will there be liability for clinicians for not reporting genetic variants associated with other health issues? And if the genome sequence is saved for future use, then when and how does the patient get to decide whether to access it? These are questions for another day, but we mustn’t forget about them entirely.

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