Keeping up with the newborn screening revolution

Key Points

Forty years since its inception, the US newborn screening program continues to evolve, adding to its cadre of benefits while still fueling debate.

Newborn screening is one of the most successful public health programs in the United States, with more than four million US newborns screened annually for various metabolic, endocrine, and hematologic disorders. This program owes its existence to Dr. Robert Guthrie, who in 1961 developed a bacterial inhibition assay that was capable of detecting elevated levels of phenylalanine-a warning sign for phenylketonuria (PKU)-from a single drop of an infant's blood.¹ The uptake of Guthrie's test was swift. By 1965, more than half of US states had established mandated newborn screening programs for PKU, and many more were actively considering implementation of a program.²

Mandated screening, however, was not instituted without debate. The program received enthusiastic support from government agencies, such as the Maternal and Child Health Bureau (MCHB), and from advocacy groups, such as the National Association for Retarded Children.³ Yet concerns about the test's validity, as well as unanswered questions about the details of treatment for PKU, caused many in the medical community, including the American Academy of Pediatrics (AAP), to delay the endorsement of mandated newborn PKU screening.² Fortunately, studies conducted after the widespread adoption of mandated screening in many states helped to answer some of the questions about the intensity and duration of treatment for PKU.^4,5

More than just the PKU test

The historical origins of newborn screening loom so large that, 40 years later, some still refer to the entire newborn screen as "the PKU test."⁷ But there are many more disorders than PKU that are assessed by state newborn screening programs. Over the past four decades, the number of disorders screened has increased in a slow and incremental fashion. This is because the number of tests that could be performed was constrained by the amount of blood collected, technical feasibility, and cost.

In the 1990s these hurdles became surmountable when researchers began using tandem mass spectrometry for newborn screening.⁸ Tandem mass spectrometry (MS/MS) is a technology used in biochemistry laboratories to identify the molecules present in a particular compound. In the case of newborn screening, MS/MS measures the levels of specific metabolic components, or biochemical markers, which are present in the blood. The patterns of these levels are used to identify possible disorders.⁹

A distinct advantage of MS/MS is that it can screen for many more disorders using the same drop of blood. Screening for multiple disorders is estimated to add just $10 to newborn screening programs-making it relatively cheap, quick, and easily expandable.⁹ It is important to note, however, that significant technical expertise is required to analyze the patterns of molecules in order to determine whether a disorder might be present.¹⁰

With the aid of MS/MS, states have been able to vastly expand the number of disorders tested as part of their newborn screening panel. For example, in 1995 states screened for five disorders on average; by 2005 that number had jumped to 24.¹¹ Many of the newly added disorders, however, are rare, with prevalence estimates as low as 1/200,000.¹² (See the Practitioners Guide for a list of the prevalence of uniform panel disorders).