Why we need to start sequencing newborns in the ICU.

Ok, I’m going to cut right to the chase here. It’s time to start sequencing babies in the NICU. It just makes sense. In fact, it’s quite stupid that we don’t. The data is there, the technology is there, the cost-effectiveness is there. We just need to pull the pieces together and do it.

The value has been shown back in 2012 by Dr. Kingsmore and colleagues at Children’s Mercy Hospital in Kansas City, MO. What Dr. Kingsmore and his colleagues had done in the NICU at Children’s Mercy was impressive. So impressive, in fact, that the US Goverment announced a $25 million program late last year to push this type of thing forward.

“One can imagine a day when every newborn will have their genome sequenced at birth, and it would become a part of the electronic health record that could be used throughout the rest of the child’s life both to think about better prevention but also to be more alert to early clinical manifestations of a disease,” says Alan Guttmacher, director of the US National Institute of Child Health and Human Development.

It now costs $1,000 or less to examine the protein-encoding portion of the genome and about $5,000 to sequence an entire human genome, so that day may be approaching quickly. And studies released over the past year have found that genetic sequencing might find a genetic cause for illness in 15–50% of children with undiagnosed diseases.” And this year, the long-awaited $1000 whole genome finally arrived.

Here’s the basic idea behind newborn ICU genome sequencing:

Background

  • >4 million babies are born each year in the United States.
  • 1 in every 20 babies born is admitted to the newborn ICU.
  • Up to 1/3 of babies admitted to a newborn ICU have genetic diseases.
  • More than 3500 single-gene diseases have been characterized, but traditional genetic testing is only available for some of them. Even if they were available, how does a physician pick the right ones? Plus, most of them cost hundreds, even thousands of dollars each. At least 500 of these genetic diseases have a known treatment.
  • Every night in the newborn ICU costs >$10,000. “A hospital stay can cost a quarter of a million dollars quite easily,” points out Dr. Kingsmore.

Why sequence newborns?

  • By conducting rapid genome sequencing and interpretation, “physicians can make practical use of diagnostic results to tailor treatments to individual infants and children,” says Dr. Kingsmore.
  • For example, babies born with the rare genetic disorder phenylketonuria (PKU) are unable to break down a certain amino acid, which can lead to brain damage and seizures. If found early enough, however, PKU is easily treated and children can move on with their lives.
  • Another example: Muscle contractions due to mutations in thesepiapterin reductase gene respond to drugs that are ineffective against other movement disorders that may look the same, but have a different genetic underpinning.
  • Symptoms of many genetic conditions, such as Charcot-Marie-Tooth(CMT), sometimes do not present until adulthood so a genetic test early on could help to save the lives of older individuals.
  • “Overall, it can save time, it can save lives, and a lot of times, it can save suffering,” Kingsmore said.

Sequencing technology

  • The study at Mercy used Illumina’s HiSeq 2500 sequencer, which can generate 120 Gigabases in 27 hours. This was in 2012. The new Illumina HiSeq X Ten announced this year, aka the $1000 genome machine, can >1.6 Terabases in about the same time period (more than 10x the sequence data). That’s 16 human genomes every 3 days. Woah.
  • After adding on time for targeted, symptom-based data analysis, Kingsmore’s group was able to get the sequencing & interpretation time down under 50 hours.

Caveats

  • Mercy’s 50 hour turnaround time did NOT include transportation or data transfer time. And many hospitals, even large medical centers, do not own genome sequencers. Not surprising since the Illumina HiSeq X Ten costs $10 million to purchase. $10 million!

The time for precision medicine is now.

Eventually, every newborn will get their genome sequenced, not just those in the newborn ICU. It just makes sense. Kingsmore’s landmark study was published in 2012. A year later, in late 2013, the US goverment announced $25 million to push newborn sequencing forward. Even where we are now, at the beginning of the genome revolution, with genomic medicine in its infancy, the benefits are clear. It’s time to pull together the pieces and change our antiquated healthcare behaviors.

Precision Medicine

A forward-looking journey through the use of genomic information to identify disease origins, develop targeted therapies, and improve outcomes.

    Reid J. Robison MD MBA

    Written by

    Eating Disorders Physician, Body Positivity Activist. Medical Director at Center for Change. Co-founded Anolinx, Tute Genomics, Polizzi Free Clinic.

    Precision Medicine

    A forward-looking journey through the use of genomic information to identify disease origins, develop targeted therapies, and improve outcomes.

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