A mission to make NICU genetic testing a standard of care

Every parent knows what it’s like to anxiously Google a child’s symptoms. For parents of critically ill babies in the neonatal intensive care unit (NICU), searching for a diagnosis brings a sense of intense desperation.

In cases where a genetic disorder causes a baby’s symptoms, rapid genome testing can deliver a diagnosis quickly. However, many neonatologists treating babies in the NICU either don’t have access to genome testing or don’t know it might provide a diagnosis.

Families are left spending years seeking an answer.

“If you cannot find a cause for an illness, it’s difficult to treat it,” says Pankaj Agrawal, M.D., MMSc, chief of the Division of Neonatology in the University of Miami Miller School of Medicine Department of Pediatrics and Jackson Health System.

Dr. Agrawal is head of a team of researchers set to change what they call a “diagnostic odyssey” –– not only for patients connected to academic medicine hospitals but also those in community hospitals with fewer resources.

As principal investigator for the Virtual Genome Center in Infant Health (VIGOR) Project, funded by a $5.4 million R01 grant from the National Institutes of Health (NIH), he and a team of researchers are partnering with 11 community hospital NICUs to provide rapid genome sequencing. They’re also educating clinicians at the partnering hospitals about how to recognize candidates for rapid genome testing and how to explain the results to families.

In addition, they are creating a special “comprehensive interpretive report” to help clinicians fully understand what the finding means in the patient’s medical care and any future research opportunities.

How does rapid genome sequencing work?

Rapid genome sequencing is like a super-powered microscope for genes. It allows a doctor to compare a critically ill newborn’s DNA (the genetic code that makes up all living beings) to a big database of genetic information from other people. This helps identify any tiny differences that might be causing problems.

Not all diseases are caused by genetic mutations, but when they are, finding the exact genetic cause of an illness can be like finding the missing puzzle piece. It helps doctors understand how the mutation is affecting a baby’s body functions and recommend the right treatment.

Genome sequencing can be used for any patient with an undiagnosed or unclear condition. The need is even higher for critically ill newborns in intensive care.

In the NICU, 15-20% of babies have a genetic condition, says Dr. Agrawal. Without access to rapid genome testing, workup for those conditions can take years. “The sooner we can diagnose them, the faster we can find treatments for those conditions. Time is of the essence for these families because they’re desperate for answers,” says Dr. Agrawal.

Some examples of unexplained symptoms that may be genetic include the following:

• Hypotonia is an example where a baby has shallow muscle tone and is very weak (sometimes severe enough to affect spontaneous breathing and/or feeding)
• Seizures with no known cause
• Severe lung or heart disease
• Metabolic issues
• Mitochondrial issues
• Some kidney issues
• Multiple congenital anomalies

With genome sequencing, diagnoses that once took years can now be determined within a week of that baby’s birth for families at participating community hospitals.

How genome sequencing benefits babies and families

Dr. Agrawal first became passionate about genetic sequencing for critically ill babies as a fellow at Boston Children’s Hospital. Families in his care spent months in the NICU without a diagnosis. “That’s why I built a center for rare diseases in Boston so that it should not be for the lack of trying,” he says.

In the years since and now, as he continues to work with Boston Children’s and builds a rare disease center in UMiami, Dr. Agrawal has seen countless families benefit from rapid genome sequencing under his care and through his research.

One family, who generously funds his research, lost a daughter from a rare recessive genetic condition. That knowledge helped them go on to have two healthy boys through pre-implantation genetic diagnosis. “After all their daughter’s suffering, they were so thankful to know the cause and prevent it from affecting their other children,” he says.

In another case of twins with seizures, it took him two years to find the cause, which was a new genetic condition. Having a diagnosis helped them know how to treat the babies. It also relieved the parents to know it was a sporadic dominant condition (not inherited) and the risk of recurrence was very low.

Researchers identify a disorder’s genetic cause in about one in three cases. 

Even getting a negative report can help. In one case of a baby who failed his newborn screening test, Dr. Agrawal’s team performed a rapid sequencing test only to find the child did not have a genetic defect. “That meant there’s a high chance that it’s nothing, and the family was so relieved not to worry about it,” he says.

Heralding the future of NICU genetic sequencing

Witnessing how a diagnosis can change the course of a child’s medical journey is why researchers at VIGOR want to bring rapid genome sequencing to all babies who need it. For the study, Dr. Agrawal says they partnered with hospitals with limited resources, care for families from diverse backgrounds and have many patients on Medicaid.

The science of discovering how genetic mutations can cause disorders and how to treat them is advancing rapidly. Dr. Agrawal, who also runs a gene discovery program, says that for every family they help, countless others are seeking answers. Sometimes, this is because a particular genetic cause has yet to be discovered. Other times, researchers know about a mutation, but those who would benefit don’t.

A family recently contacted Dr. Agrawal about their son’s condition that kept him hospitalized for six of his nine months of life. When they finally accessed genome sequencing, they found a gene that Dr. Agrawal’s team had identified a year before as part of their gene discovery efforts. 

“You realize this is such important work to help them so that they can move on from identifying the problem to finding treatment,” he says.

The struggle and strength of the families keep him motivated. 

“I see how much pain they are going through, and then they see a glimmer of hope that we can find the cause. They appreciate what we’re doing, and you want to do it for everyone who needs it.”

Wendy Margolin is a contributor to UHealth’s news service.

Tags: Disease Prevention, Dr. Pankaj Agrawal, genetics program, neonatology