Newborn genomic screening may detect hundreds of additional childhood conditions

Adding genomic sequencing to newborn blood screening would detect hundreds of additional childhood conditions, providing much earlier diagnosis and treatment, according to a new study. A baby's genome, which stays with them for life, could also be re-examined if a health issue arises during their lifetime.

The study, led by Murdoch Children's Research Institute (MCRI) and Victorian Clinical Genetics Services (VCGS), found genomic screening, a test that reveals a person's entire genetic makeup, could easily be included as part of the newborn heel prick test and deliver results for hundreds of treatable conditions within 14 days. The heel–prick test, which is offered to all Australian babies a few days after birth, covers 32 conditions.

Results from the BabyScreen+ study, published in Nature Medicine, showed genomic testing was acceptable to parents and feasible using the same sample collected for the heel–prick test.

The study screened 1,000 newborns in Victoria for changes in 605 genes associated with early-onset, severe, treatable conditions using genome sequencing. The research was conducted separately from the newborn bloodspot screening program, with study participants needing to provide further consent for their newborns to undergo genomic testing.

It found 16 babies had an increased likelihood of a genetic condition. Of these, only one was detected by the standard newborn screening. One baby was diagnosed with a rare and severe immunodeficiency disorder with the early diagnosis enabling rapid treatment, including a successful bone marrow transplant. 

Zornitza Stark, also a VCGS Clinical Geneticist, said the pilot study highlighted that genomic newborn screening could be lifesaving as more babies would be rapidly diagnosed and treated.

Newborn screening for rare conditions is one of the most effective public health interventions," she said. "But the increased capacity of genomic medicine to diagnose and treat rare diseases has challenged the ability of newborn screening programs to keep pace.

Our study found incorporating genomic sequencing provides the opportunity to substantially expand the range of conditions screened for, including those that predispose people to childhood cancers, as well as cardiac and neurological disorders, not detectable with current standard technologies."

Zornitza Stark, MCRI Professor 

Parents of the newborns enrolled in the study said they were glad to have taken part, with 99.5 per cent believing the testing should be available to all babies, and 93 per cent willing to recommend it to family and friends.

MCRI and VCGS Associate Professor Sebastian Lunke said, "Genomic sequencing at birth would enable many newborns to be diagnosed and treated earlier, improving patient and family health outcomes. It could also potentially be vital to lifelong health, with the data stored and available to screen at any time."

But Associate Professor Lunke said there were practical and ethical concerns with newborn genomic sequencing, and issues including cost, equity, data storage, access and maintaining ongoing consent as a child becomes an adult would need to be addressed.

"Generating genomic data introduces complexities spanning privacy, data usage and, potentially, insurance implications," he said. "We need to carefully think about how and when this information is best presented to parents to enable considered and informed choices.

"In Australia we need to progress this research to make sure our healthcare system makes decisions on robust evidence and builds the capacity to harness this technology responsibly on a mass scale."

It was Justin and Scarlett's daughter Giselle who was diagnosed at seven weeks with the immunodeficiency condition, hemophagocytic lymphohistiocytosis (HLH), through BabyScreen+. The condition had not been picked up via genetic carrier screening.

Prompt diagnosis and treatment are critical, as HLH can be life-threatening if undetected, causing widespread inflammation, organ damage and central nervous system and neurological problems.

"I just cried once we received the diagnosis," Scarlett said. "We went from thinking we had a healthy baby to the real possibility she might die." "Giselle was a very sick baby, but she didn't look unwell. We knew nothing about HLH so we were in the dark about how sick she could get."

To treat HLH, Giselle required a bone marrow transplant. After the original full match donor fell though, Scarlett became the donor, providing a half-match.

The transplant was a success, but Giselle spent months in hospital and, due to complications, required a stay in in intensive care for several weeks.

Justin said having since recovered and leaving hospital earlier this year, Giselle, now 14 months, had a promising future ahead of her thanks to the genomic test. 

"Despite a really challenging and at times heart-breaking process, we were so relieved to have a prompt diagnosis and clear treatment plan," he said. "BabyScreen+ has been a huge benefit to Giselle's health, allowing her to avoid many long-term complications.

"If BabyScreen+ didn't exist we'd be coming from a standing start instead of running start. We were ahead of the game, which allowed her medical team to act quickly. Everyone should have access to genomic screening."