Regional report March 17th 2016

Regional news: A report from North America

Newborn screening in the United States

Newborn screening (NBS) expansion is once again gaining momentum in the United States with many disorders being considered due to promising new treatments, better testing methods and other factors that impact the decision making process. Three factors that have helped shape the NBS landscape in the U.S.

The first factor was the implementation of a transparent and systematic approach to determine the disorders to be recommended for inclusion. This was accomplished by the formation of the Secretary’s Advisory Committee on Heritable Disorders in Newborns and Children (SACHDNC). The committee is composed of a broad range of NBS stakeholders who objectively follow specific guidelines to prioritize the disorders to be added. This committee works at the federal level within the Health Resources Service Administration (HRSA) to make recommendations to the Secretary for Health and Human Services (HHS). The development of guidelines and selection of over one hundred disorders for initial review, was contracted by SACHDNC to the American College of Medical Genetics (ACMG). After many meetings and public hearings, the guidelines and recommendation resulted in 29 disorders being recommended for screening throughout the U.S. Though not a mandate, this recommendation served to establish a universal screening model that each state has since adopted.

The second factor was the improvement of technology. Several pioneers of NBS in the early 2000s recognized the multiplexing capabilities of mass spectrometry (MSMS) while manufacturers have improved the robustness of their systems. Now, more than 40 disorders can be detected from one single dried blood spot and hundreds of samples analyzed daily. The shear volume of information generated from MSMS has also spurred the development of new data management tools that have evolved to sophisticated quantitative algorithms that use multiple analytes, ratios, and reliability formulas, as “post analytical tools” to decreasing the false positive rates and thus, parental anxiety and cost.

The third factor was an increase in research leading to treatment for these rare disorders. While it takes many years for a new drug candidate to be approved, SACHDNC monitors these trials and holds public hearings to review the impact of better therapy on NBS. While there is ongoing debate as to whether a disorder with no treatment should be included in a NBS panel, many advocates contend that simply knowing what disorder a newborn has, whether it is treatable or not, reduces the medical odyssey of concerned parents and gives the physician more information to provide genetic counseling.

Many would agree that the foundation laid by SACHDNC and ACMG has increased both awareness and education within the US as well as the need by other countries to identify internal leaders, establishing a committee of empowered experts and institutionalizing a transparent decision making process when considering how to implement a newborn screening program.

Recent and future developments

Several disorders have been added to the recommended panel since the first twenty-nine were selected. Critical Congenital Heart Disease (CCHD) was added to the panel as a point-of-care (POC) test performed at the newborn’s bedside. It currently involves the use of a pulse-oximeter attached to the baby’s finger without the need for drawing blood.
Severe Combined Immunodeficiency (SCID), also known as “Bubble Boy Disease” is the first NBS disorder that can be cured if a stem cell transplant occurs within three months of birth. It was the development of a PCR assay, the first PCR to be used in NBS, to detect T-cell receptor activity that ultimately allowed SACHDNC to include SCID in the panel. The results have shown that this disorder, albeit rare, is up to three times more common than originally had been predicted. At this time, approximately two thirds of the U.S. and some Canadian provinces have implemented SCID screening.
In 2013, Pompe Disease was added to the panel. In 2014, MPS1 was recommended by SACHDNC to the HHS Secretary for inclusion, but it has not yet been approved.
An evidence based review of X-linked Adrenoleukodystrophy (X-ALD) was presented on August 27. At this time, a vote of 14-1 to send the recommendation to the HHS secretary for final approval.

Stakeholders interested in screening for Duchenne’s Muscular Dystrophy (DMD) and Urea Cycle Deficiency are currently compiling data to submit a nomination to SACHDNC.
Both California and the CDC recently completed a study showing that the detection of Cytomegalovirus (CMV) is feasible in NBS. It is screened for in Japan. At this time, a nomination to SACHDNC has not been made.