Analytical Perspectives on the Use of Dried Blood Spots and Mass Spectrometry in Newborn Screening

Abstract Newborn screening is a public health program that aims to detect genetic disorders shortly after birth so that diagnosis and treatment can be provided early and therefore provides the best possible outcome for affected infants. Dried blood spots are a unique specimen that is utilized by all laboratory‐based methods in newborn screening. The volume of blood available for each test is less than 10 μL and therefore requires microsampling analytical techniques. The concentration of metabolites obtained from a dried blood spot ranges from a few hundred micromolar for some amino acids to femtomolar for hormones such as thyroxine. Tandem mass spectrometry is uniquely suited to sensitively and selectively detect many metabolites of different chemical classes using a single analytical method (amino acids, l‐carnitine and fatty acylcarnitines, and succinylacetone). Metabolic profiles of these metabolites provide both quantitative and qualitative information that helps detect the largest number of disorders in a newborn screening panel with fewer false results than many historic technologies it has replaced. Mass spectrometry is also a versatile tool that confirms diseases detected by other screening methods and will continue to expand.