Abstract

The expansion of newborn screening through whole-genome sequencing (WGS) represents a transformative shift 
from targeted biochemical testing toward comprehensive genomic population screening. This paper examines the 
potential benefits, harms, and public-health decision frameworks guiding the adoption of WGS in newborn 
screening programs, synthesizing current evidence and identifying key knowledge gaps. WGS offers the capacity 
to detect a broader spectrum of genetic disorders at or before symptom onset, improve diagnostic yield, and enable 
earlier clinical intervention and lifelong risk management. However, its implementation introduces substantial 
challenges, including incidental findings, uncertain variant interpretation, consent complexities, data-privacy 
concerns, inequities in access, and increased follow-up burdens on families and health systems. Public-health 
decision frameworks, such as cost-effectiveness analysis, value-of-information approaches, and phased pilot 
implementation, provide structured tools to balance potential benefits against risks while ensuring transparency 
and accountability. Despite growing international pilot programs, evidence on long-term clinical utility, 
population-level outcomes, economic sustainability, and ethical governance remains limited. Addressing these 
uncertainties requires coordinated research, robust infrastructure, and inclusive policy development. Overall, while 
WGS-based newborn screening holds significant promise for improving early detection and preventive health 
strategies, careful evaluation of its clinical, ethical, and societal implications is essential before large-scale adoption.