A large-scale newborn genomic screening program in New York City found that most parents agreed to testing and found there was a 3.7% rate of detection of variants that cause disease. This included some variants for treatable conditions not currently included in regular newborn screening. Notably, this was a racially and ethnically diverse set of parents.
In the study, 72.0% of approached families consented to participate and genome sequencing was successfully completed for 99.6% of participants. 156 early-onset genetic conditions with established interventions selected by the investigators were screened in all participants and 99 neurodevelopmental disorders associated with seizures were optional.
The report was published in JAMA Network and led by Alban Ziegler, MD from the Columbia University Irving Medical Center in New York City.
A big focus of the study was to see how parents responded to the offer of screening, and to see how diverse the respondents were. In this interim study, over 11 months, 5,555 families were approached and 4,000 (72.0%) consented to participate. Enrolled participants reflected a diverse group by parent-reported race.
“These interim findings demonstrate the feasibility of targeted interpretation of a predefined set of genes from genome sequencing in a population of different racial and ethnic groups,” wrote Jonathan S. Berg, MD, PhD, of The University of North Carolina at Chapel Hill, who wrote an accompanying editorial.
The Genomic Uniform-screening Against Rare Disease in All Newborns (GUARDIAN) study was a multisite, single-group, prospective, observational investigation of supplemental newborn genome screening with a planned enrollment of 100,000 participants. Parents were recruited for the research study after their newborn’s delivery, with 72% ultimately enrolling.
“DNA sequencing offers an additional method to improve screening for conditions already included in NBS and to add those that cannot be readily screened because there is no biomarker currently detectable in dried blood spots,” wrote Ziegler and colleagues.
Berg wrote, “The GUARDIAN study reflects growing interest in preemptive identification of monogenic diseases in the general population, with the goal of ameliorating or preventing their associated poor health outcomes. Like all other screening initiatives in medicine, genomic screening must address the question of test performance.”
He added that, “Genomic screening is fundamentally different because it involves the direct identification of genetic variants that are putative causal actors in monogenic conditions, thereby predicting that an individual is at risk for developing manifestations of that condition. One of the challenges is how performance can be benchmarked and what types of false-positive and false-negative results we should be attentive to when implementing population-wide screening.”
