Newborn Screening Primer

Posted by Gabor Bethlendy

Mar 6, 2014 10:48:00 PM

As we continue this series of posts on Newborn related topics we thought it makes sense to cover at a high level the history of Newborn Screening and hint at some of the challenges we face moving the field to the next stage of catching these disorders. Many fo these challenges will be covered in follow-up posts in greater detail.


Newborn screening (NBS) is one of the largest and most successful public health programs, first introduced in 1963 for phenylketonuria (PKU) by Dr. Robert Guthrie, from dried blood specimen (DBS) and is now routinely performed on all newborns. Since 1990s Dr. Edwin Naylor and his colleagues streamlined NBS by utilizing mass spectrometry, which today is the defacto ‘gold standard’. However, even after 50 years of NBS, only 29-50 disorders are screened in the newborn period (of the possible 7000 Rare Diseases) and introduction of new conditions for screening is constrained by clinical actionability. Other factors affect mass spectrometry based measurements such as prematurity related factors that affect analyte levels in blood, which require second-tier testing beyond the initial NBS. Furthermore, in many cases when symptoms develop the infant is admitted to intensive care unit, but a comprehensive genetic test that can assist in genetic diagnosis or differential diagnosis is unavailable. The challenges in such situations are not only nominating the condition related genes and its corresponding tests but also utilizing DBS based NGS that until now were not possible. Lack of such a test leaves neonates without a follow-up and healthcare providers without sufficient proof of the genetic basis of diseases to make informed clinical decisions. Diagnosis for Rare Genetic Diseases beyond the newborn period also remains challenging, and collectively, these diseases are a significant portion (~17%) of the pediatric hospitalization cost in the Western World. Almost 25% of children with Rare Genetic Diseases die within the first year of life, and the rest experience effects of their disease or misdiagnosis that can cause enormous life-long suffering.

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Targeted Next Generation Sequencing based testing implemented at birth as a reflex test for NBS or in NICU or pediatric diagnosis will provide genetic predisposition knowledge. Providing mutational information on rare disorders has the same potential to reduce incidence through improved family planning as with the ~90% reduced incidence of Tay Sachs in the Jewish population since screening was introduced.