The Wadsworth Center Newborn Screening Program has participated in the GUARDIAN newborn genome sequencing study since 2022. GUARDIAN is a research study that screens newborns for 321 to 465 genetic conditions, most of which are not included in the standard New York State newborn screening process. With informed consent, the GUARDIAN panel is offered to families of newborns delivered at select New York City hospitals. Testing uses DNA extracted from residual blood samples collected for newborn screening, followed by genome sequencing and targeted analysis. The study seeks to identify infants with conditions not currently screened for and to evaluate the utility of genome sequencing at birth.
The study includes two groups of conditions. Group 1 includes 321 serious conditions for which treatment or intervention can prevent or lessen symptoms. Group 2, which is optional, includes 144 additional conditions for which early diagnosis may support future treatment, clinical-trial enrollment, or early intervention services such as physical, occupational, and speech therapy.
Researchers retrospectively compared two analytic approaches using data from the first 12,500 enrolled infants. The current pilot approach reports selected variants of uncertain significance. An alternative, more automated approach limited reporting to pathogenic and likely pathogenic variants identified through publicly available data. Although the automated approach increased specificity by reducing false-positive results, it reduced sensitivity for some treatable conditions. Notably, most infants whose conditions would have been missed under the automated approach were of non-European ancestry. This highlights the importance of maximizing equitable screening practices by carefully assessing variants for which evidence is not yet sufficient to support a pathogenic or likely pathogenic classification.
Participation in externally funded pilot programs and translational research allows the Newborn Screening Program to evaluate emerging technologies, assess feasibility, and strengthen and expand screening in ways that can improve health outcomes for New York State infants.