Why Tandem Mass Spec is Essential for Newborn Screening

Mass spectrometry enables clinical laboratories to keep pace with screening millions of newborns for dozens of disorders

Put simply, newborn screening gives us this chance to identify babies who may become ill before they do become ill. This screening is performed in the early newborn period so that children at risk can be identified, treated, and further health problems may be prevented.

Newborn screening (for phenylketonuria or PKU) began in the United States in the mid-1960s. Fast-forward 50 years and approximately 12 million babies (in some places for greater than 30 inborn disorders!) are screened per year worldwide. In the next five to ten years, that number is expected to increase to 60 million babies per year thanks to the emergence and expansion of newborn screening programs globally.

The technology used for newborn screening has changed dramatically over the last 50 years. It began with relatively simple, robust techniques, that were specific for the particular metabolite(s) and conditions that were trying to be identified. Dr. Robert Guthrie’s original screening method – a bacterial inhibition assay – allowed scientists to identify high concentrations of phenylalanine in newborn dried blood spots incubated in agar plates impregnated with bacteria that would grow well in the presence of those high concentration of phenylalanine. Thus it was possible for the first time to rapidly and inexpensively screen entire populations of newborns for this life altering metabolic disease.

A breakthrough came in the mid-1990s with the discovery that by linking electrospray ionization (ESI) to mass spectrometry, a robust quantitative method using a tandem quadrupole mass spectrometer to measure elevation blood levels of phenylalanine and a range of other compounds that were key signatures for other inborn metabolic disorders, was possible.

Across the world people began to adopt tandem mass spectrometry as a cost effective and analytically superior solution.

It was a game changer because rather than having a single test for a single condition, there was now a technique that provided a single test for a large number of different conditions.

To say that mass spectrometry has had a huge impact on newborn screening would be an understatement.  Scientists are now learning to make more intelligent use of the valuable data that they can now obtain. With the ability to perform second-tier testing and the use of metabolite ratio that mass spectrometry provides, they can better predict if a screening result is truly positive or negative.  This will become an even more important aspect to enhance screening moving forward.

With improved technology and enhanced data, there has also been an increase in collaboration. Scientists from all over the world are sharing their experiences, knowledge, and methods for newborn screening. As a result, the next 50 years of newborn screening has the potential to be even more impactful than the first 50, so that more babies born with conditions that may once have led to disability or even death, have the opportunity to grow up to be healthy adults.

Read more:

• The Historical Role of Mass Spectrometry in Newborn Screening