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Expanded newborn screening offers early diagnosis, treatment of infants with SCID

Testing of newborns for severe combined immunodeficiency reveals higher disease rates than previously believed

Beverly Hay, MD
Anne Marie Comeau, PhD

Anne Marie Comeau, PhD, (left) and Beverly Hay, MD

Using population-based screening outcomes of approximately 3 million infants, a team of scientists across 14 states, including four researchers at UMass Medical School, have shown that newborn screening for severe combined immunodeficiency (SCID) can be successfully implemented across public health newborn screening programs. Data from 11 newborn screening programs published in the Aug. 20 issue of the Journal of the American Medical Association (JAMA) showed the rate of SCID in newborns is higher than previously thought and believed to be 1 in 58,000.

“This paper is an excellent example of translational science and medicine yielding the successful public health system necessary for early diagnosis and treatment of SCID,” said Anne Marie Comeau, PhD, deputy director of the New England Newborn Screening Program and professor of pediatrics at UMMS.

Newborn screening programs enable early detection of conditions for which prompt treatments can reduce the risk of death or irreversible damage. The first heritable immune disorders to which newborn screening has been applied are those that together comprise severe combined immunodeficiency. SCID babies are born without a developed immune system and are subject to a wide variety of life-threatening infections. However, the advance of stem cell transplantation to replace the immune system, coupled now with the opportunity to identify SCID early through newborn screening, holds the promise that affected children can lead normal, healthy lives. Early detection is critical for treatment of SCID and, in most cases, population-based testing through newborn screening programs is the only means to detect SCID prior to the onset of infections.

Unlike other conditions included in newborn screening, SCID requires a DNA-based testing strategy for every infant screened. In 2008, Wisconsin and Massachusetts were awarded grants from the Centers for Disease Control to develop, demonstrate and transfer testing strategies that could be adopted by other newborn screening programs. With data generated by these pilot programs, SCID was added to the national recommended uniform panel for newborn screened disorders in 2010. Currently 23 states, the District of Columbia and the Navajo Nation screen approximately two-thirds of all infants born in the United States for SCID.

The New England Newborn Screening Program, which is operated by the UMMS on behalf of the Massachusetts Department of Public Health, has been performing newborn screening in Massachusetts since 1962 and now provides screening for about 500 newborns every day in Massachusetts, Maine, New Hampshire, Rhode Island and Vermont; SCID screening has been offered statewide in Massachusetts since early 2009 and Maine and Rhode Island recently authorized the New England Newborn Screening Program to test infants for SCID.

“As the second state to implement screening for SCID, we are proud to have contributed to the development of algorithms for early detection and treatment of these rare disorders,” said Beverly Hay, MD, chief of pediatric genetics at UMass Memorial Medical Center and assistant professor of pediatrics at UMMS.

Antonia Kwan, PhD, MRCPCH, of the University of California, San Francisco, and collaborators, including members from the Massachusetts SCID Newborn Screening Working Group, conducted the analysis of more than 3 million infants screened for SCID in 10 states and the Navajo Nation. Infants born from the start of each participating program from January 2008 through the most recent evaluable date prior to July 2013 were included.

There were 52 SCID cases identified within the cohort, for an overall incidence of 1 in 58,000 births, up from the previous estimate of 1 in 100,000 births.

The incidence was not significantly different in any state program but was higher in the Navajo Nation (1/3,500), attributed to a genetic mutation found in this population. Survival of SCID-affected infants through their diagnosis and immune reconstitution was 87 percent, and 92 percent for infants who received transplantation, enzyme replacement and/or gene therapy. Additional interventions for SCID and non-SCID T-cell lymphopenia (abnormally low level of certain white blood cells) included immunoglobulin infusions, preventive antibiotics and avoidance of live vaccines. The observed short term outcomes confirm the benefit of newborn screening as was recently predicted by the retrospective study of transplantation outcomes from Pai et al (NEJM371:5 July 31, 2014).  

“It’s a pleasure to see that Massachusetts’ early efforts with Wisconsin and the Centers for Disease Control to ensure high quality, high-throughput DNA-based screening and clinical protocols have been fruitful,” said Dr. Comeau. “When emerging technologies that require technical competence, protocol sharing and training are combined with appropriate clinical expertise and integrated within the public health system, there is a positive effect on babies’ lives. The study shows that multiple states, all participating in quality assurance programs run by the CDC, implemented a new technology and many babies benefited.”

“The incidence of SCID was found to be higher than previously estimated, suggesting that SCID was likely under-recognized and underdiagnosed in the past. Early detection allows for treatment before a child becomes overwhelmingly ill, which leads to a better outcome for that child” said Dr. Hay.