Early findings from a study involving 4,000 newborns indicate that genome sequencing can identify a significantly higher number of serious health conditions compared to standard newborn screening methods, and this approach is preferred by most parents.
Initial outcomes from a research project on newborn screening techniques reveal that DNA sequencing detects many more preventable or treatable severe health issues than traditional newborn screening methods, and a majority of parents support this option.
The study, named GUARDIAN, is among the first large-scale investigations globally utilizing genome sequencing for newborn screening and is the first to publish its preliminary findings.
According to Joshua Milner, a Pediatrics professor, and co-author of the study, “These findings demonstrate that genome sequencing can significantly enhance the medical treatment of children.” Milner holds the position of allergy, immunology, and rheumatology director at the Columbia University Vagelos College of Physicians and Surgeons, and he also works at the NewYork-Presbyterian Morgan Stanley Children’s Hospital.
Milner elaborates, “This form of sequencing enables us to identify critical illnesses and take preventive measures for a substantial number of children, not merely a few isolated cases. It ought to become the new standard for newborn screening since it uncovers far more than existing methods.”
In genome sequencing, a newborn’s DNA is examined for hundreds of specific genetic variants associated with diseases. This technique holds the promise of identifying thousands of genetic disorders, vastly outnumbering the roughly 60 conditions currently detectable by standard newborn screening. The genes targeted in newborn screening are those that lead to diseases that may be prevented or managed if detected during early infancy.
Out of the initial 4,000 infants in the GUARDIAN study, genome sequencing revealed 120 children (3%) with serious health issues, with only 10 of those being flagged by traditional screening methods. For one infant, discovering a rare gene variant responsible for a severe immunodeficiency that standard screening failed to detect made a life-saving bone marrow transplant possible.
Wendy Chung, a physician-scientist, and the Principal Investigator of this study, states, “In my experience, I’ve seen numerous patients struggling for years with unexplained symptoms, only to receive a diagnosis when the opportunity for optimal disease management has already passed.” She initiated the research during her time at Columbia University and now leads the pediatrics department at Boston Children’s Hospital. “Thanks to genomic technology, families and pediatricians no longer have to go through those complex diagnostic journeys. We can now provide a diagnosis at birth.”
Background
In the U.S., about 1 in 300 newborns is diagnosed with a treatable health condition identified through standard newborn screening. Since the 1960s, newborn screening has broadened to include various genetic diseases. The Health Resources and Services Administration suggests screening for up to 63 conditions, though the actual screening panel differs by state.
Jordan Orange, co-author of the study and chair of pediatrics at Columbia University, emphasizes, “Newborn screening has been a monumental achievement in public health. It levels the playing field in healthcare by guaranteeing that all babies receive the same screening, giving every child an equal chance for a healthy life.”
Standard newborn screening identifies biomarkers in blood samples linked to various disorders. However, the absence of identified blood biomarkers for many conditions hampers the effectiveness of screening.
Once thought to be rare and prohibitively expensive, genome sequencing is becoming more accessible and affordable, making it a promising alternative for newborn screening.
“We are experiencing a transformation in pediatric medicine and recognizing that many more childhood conditions have genetic origins than previously believed,” Milner notes. “This expansion reshapes our understanding of what we should be screening for.”
The GUARDIAN study currently examines gene variants associated with over 450 conditions and continues to identify numerous new conditions each year.
“It would be impractical to test for all these conditions using traditional methods,” Orange states, “but with genomic screening, adding new conditions comes with minimal extra cost. We can explore treatable ailments we had not previously considered for screening.”
The Study
Initiated in September 2022, the GUARDIAN study offered genome sequencing to each newborn at hospitals affiliated with NewYork-Presbyterian in New York City.
In its first year, GUARDIAN screened for genes linked to 156 rare yet treatable conditions. Parents could also choose to screen for an additional 99 conditions currently lacking treatment, which could nonetheless benefit from early intervention.
The research utilizes DNA collected from the same dried blood spots used for standard newborn screening, conducted by the New York State Department of Health’s Newborn Screening Program for all participants.
The findings published in the October 24 edition of JAMA detail the results from the first 4,000 newborns born between September 2022 and July 2023. Over 12,000 infants have participated in the study since it started.
Findings
Of the 147 children identified as positive through genome sequencing, 120 were correctly diagnosed with a rare condition. Only 10 of these cases were flagged by traditional screening.
Most diagnosed children (92 out of 120) were found to have glucose-6-phosphate dehydrogenase deficiency (G6PD), an enzyme deficiency not included in standard newborn screening. People with G6PD deficiency can experience severe allergic reactions to certain foods and medications, which can be easily avoided with precaution.
Additionally, genome sequencing uncovered a severe condition—severe combined immunodeficiency disorder (SCID)—that standard screening failed to detect in one child. The identification of a rare genetic variant linked to SCID allowed healthcare providers to safeguard the infant against potentially fatal infections before any symptoms emerged.
Milner states, “We understand that a bone marrow transplant can cure these children, but the safety and success rate are highest when performed in the early months of life, before any infections or symptoms arise. The timely identification of this child was solely due to genomic screening.”
Overall, 3.7% of the children in the study tested positive for a genetic condition. Excluding G6PD cases, the positive screening rate drops to 0.6%, which is double the 0.3% rate typical in standard New York state screenings.
Milner asserts, “This is just a baseline figure. Implementing this type of screening will lead to increased detection rates as we expand our condition list.”
Parents showed a strong approval for using genome sequencing in newborn screening, with 72% of families agreeing to participate, and the majority (90%) choosing to include the optional tests for untreatable conditions.
Remaining Questions
The ongoing GUARDIAN study aims to enroll 100,000 infants in the coming years to better comprehend parents’ perceptions of genome sequencing, examine the costs associated with such programs, address privacy concerns, and explore challenges in interpreting results among various ancestry groups.
Increasing the scale of genome sequencing will heighten screening costs. If the GUARDIAN study’s screenings were applied to the 210,000 infants born annually in New York state, about 7,700 of those would likely test positive. As more children are screened, total costs will increase due to the necessity for follow-up testing for those with positive results.
Milner notes, “These expenses must be weighed against the potential costs if a child develops a condition that could have been treatable if caught sooner, along with the value of preventing illnesses. Ultimately, the question lies in who will shoulder these expenses. Given that genomic screening can identify many more conditions, prevent more illnesses, and save lives, the added expense may justifiable.”
