A recent large-scale newborn genomic screening program in New York City has revealed significant parental interest and a notable rate of disease-causing variant detection. The study, published in JAMA Network, found that 72% of approached families consented to participate in the Genomic Uniform-screening Against Rare Disease in All Newborns (GUARDIAN) study.
The screening successfully completed genome sequencing for 99.6% of participants and identified a 3.7% rate of variants associated with early-onset genetic conditions. This included variants for treatable conditions that are not currently part of routine newborn screening. The study screened for 156 early-onset genetic conditions with established interventions and 99 neurodevelopmental disorders associated with seizures (optional).
Parental Response and Diversity
The study emphasized assessing parental response to the screening offer and ensuring diversity among respondents. The enrolled participants represented a diverse group based on parent-reported race, highlighting the feasibility of targeted interpretation of a predefined set of genes from genome sequencing in various racial and ethnic groups.
Improving Screening Methods
According to Alban Ziegler, MD, from Columbia University Irving Medical Center, "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."
Challenges and Considerations
Jonathan S. Berg, MD, PhD, of The University of North Carolina at Chapel Hill, noted that genomic screening 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. He emphasized the importance of addressing test performance, potential false-positive, and false-negative results when implementing population-wide screening initiatives.
