How rapid sequencing in the NICU plays out

Summary

Rapid genome sequencing in neonatal intensive care units is a complex process involving a multidisciplinary team, including pathologists, genetic counselors, and clinicians. The goal is to identify genetic causes of complex medical conditions in newborns, often born prematurely with multiple health issues. The process involves analyzing vast amounts of genetic data, prioritizing relevant variants, and providing clear, actionable information to clinicians and families, all while navigating the challenges of uncertain results and the urgency of time-sensitive decisions.

Karen Titus

February 2026—It’s tempting to reach for metaphors when talking about rapid genome sequencing in neonatal intensive care units. The topic is a tangled one.

Which is why it’s helpful that Paweł Mróz, MD, PhD, associate professor, hematopathology and molecular genomics, University of Minnesota Medical School, tends to talk about the testing as a team sport. And that his colleague, Matthew Bower, MS, LGC, a genetic counselor with the molecular diagnostics laboratory and neurology clinic, University of Minnesota Medical Center, brings up the notion of slam-dunk answers. And it’s why those doing the testing keep a coach-like eye on the clock. “We cannot lose a single hour,” says Saurav Guha, PhD, director, molecular diagnostics, New York Genome Center.

But what NICU sequencing might most resemble is a game of chess (though many contend this too is a sport), with laboratories maneuvering among current and possibly future medical conditions, for both the patient and the patient’s family; weighing the input of pathologists, molecular geneticists, clinician specialists, and genetic counselors; searching through vast numbers of genes and variants for answers that are rock-solid, or possibly helpful, or of uncertain significance—knowledge that is ever-changing; and striking a balance between what the results reveal to those in the laboratory, and what clinicians and families actually want to know.

Welcome to chess in the multiverse.

The opening move is best gleaned from the particulars of each patient and answering a fundamental question: What problem is sequencing trying to solve?

Bower lays out common scenarios.

In some cases, he says, “You’re looking at a really, really sick kid, where they’re making decisions about whether to discontinue heroic efforts. Is this a child [who’s] eventually going to go home, or not?

“If you arrive at a genetic diagnosis that is crystal clear,” he continues, “that can be helpful in planning.” For a child born with a complex cardiac condition, for example, physicians might be weighing whether to perform an incredibly risky surgery. If there’s an underlying genetic condition that may point to a poor outcome regardless, “the providers and family might approach that differently than a case with no apparent genetic indication.”

There’s also the subjective—“but very important,” Bower says—value of naming things for patients. “Knowing what the name is, knowing what they’re up against, can be an invaluable piece of psychosocial information.” It can also give them what Bower calls anticipatory information—knowing that an identified genetic condition may point to the need for further workup.