Screening newborns for lethal immune diseases saves lives

Introducing widespread newborn screening for a deadly disease called severe combined immunodeficiency, or SCID, followed by early treatment increased the five-year survival rate of children with the disorder from 73% before the advent of screening to 87% since then, report the researchers. . Among children whose disease was suspected because of newborn screening rather than disease or family history, 92.5% survived five years or more after treatment. These findings demonstrate for the first time that newborn screening facilitates early identification of infants with SCID, leading to prompt treatment before life-threatening infection occurs and thereby increasing the proportion of children surviving to age 5 years or older. Researchers at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and colleagues led a retrospective study, which Lancet published today.

“This study definitively demonstrates that population-wide SCID screening of newborns has made it possible to save the lives of more children with the disorder than ever before,” said NIAID Acting Director Hugh Auchincloss, MD. “We hope these findings will encourage more countries to screen newborns for this devastating disease.”

SCID is a rare disorder caused by mutations in genes involved in the development and function of infection-fighting immune cells. Babies with SCID appear healthy at birth but are very susceptible to severe infections. This condition is fatal, usually within the first year or two of life, unless the baby is receiving immune restoration treatments such as a stem cell transplant, gene therapy, or enzyme therapy. Forty to 80 babies in the United States and Canada are diagnosed with SCID each year. The number of babies born with the disorder globally is unknown because most countries have not screened for SCID. The incidence ranges from 1 baby per 2,000 live births in areas where inbreeding is common to 1 per 60,000 live births where it is not.

NIH scientists developed the SCID screening test in newborns in 2005. The phased application of the test has made it possible to detect disease in infants before symptoms appear, take steps to prevent infection, and provide life-saving treatment early. Each US state and Canadian province began screening newborns for SCID in 2008, starting with a pilot program in Wisconsin. As of late 2018, all US states, Washington, DC, and two US territories are screening newborns for the disorder. Seven Canadian provinces and territories currently do so.

Some previous studies have suggested that screening newborns for SCID improves survival, but none have proven this. For this reason, the NIH-funded Consortium for Treatment of Primary Immune Deficiencies (PIDTC) set out to definitively measure whether the advent of population-wide newborn screening for SCID has improved the overall survival of infants with this disease. PIDTC is part of the NCATS Rare Disease Clinical Research Network and comprises 47 centers in North America with the common goal of improving the health outcomes of people with rare, life-threatening, and inherited immune system disorders.

PIDTC researchers analyzed data on more than 900 children with confirmed SCID who received treatment for the condition by transplantation of blood-forming stem cells from genetically mismatched donors at one of 34 sites in the United States or Canada between 1982 and 2018. The researchers examined the five-year overall survival rates of these children from 2010¬–2018, when statewide and provincewide newborn screening was in effect at participating sites, compared with the previous time period. The researchers excluded babies who received stem cell transplants from genetically matched sibling donors from the analysis, because these children had high overall survival rates during the study period.

The five-year overall survival rate for children with SCID who received stem cell transplant from a genetically mismatched donor remained stable at 72% to 73% from 1982 to 2009 despite advances in clinical care, then increased to 87% during 2010 to 2018. Among children whose disease was first suspected on the basis of newborn screening results rather than disease or family history of SCID, and who received a transplant between 2010 and 2018, 92.5% survived to age 5 years or older.

Previous research has shown that being younger than 3.5 months at the time of transplant and not having an active infection at that time increases the five-year survival rate for children with SCID. Analysis of the PIDTC data shows that these two factors are far more common in the newborn screening era and are driving an increasing proportion of children surviving to age 5. In addition, in 2010–2018 compared to the previous decade, the percentage of infants with SCID who had never developed an infection at the time of transplantation was dramatically higher, further driving increased survival. In addition, regardless of the transplant technique used, the percentage of children surviving to the age of 5 was highest in 2010-2018 compared to the previous decade.

NIAID and NIH’s National Center for Advancing Translational Sciences funded this research with additional support from NIH’s National Institute of Neurological Disorders and Stroke; National Heart, Lung, and Blood Institute; and the National Cancer Institute.

Luigi Notarangelo, MD, Christopher Dvorak, MD, Elie Haddad, MD, Ph.D., and Monica Thakar, MD, led the research. Dr. Notarangelo is head of the NIAID Clinical Immunology and Microbiology Laboratory. Dr. Dvorak is chief of the Division of Pediatric Allergy, Immunology and Bone Marrow Transplant and director of the Pediatric Cellular Therapy Laboratory at the University of California San Francisco (UCSF). Dr. Haddad is chair of the study and professor in the Department of Pediatrics at the University of Montreal, as well as head of the Division of Immunology, Rheumatology and Allergy at CHU Sainte-Justine in Montreal. She also serves as the Bank of Montreal chair of pediatric immunology at CHU Sainte-Justine. Dr. Thakar is the medical director of the Bone Marrow Transplant Inpatient Service at Seattle Children’s Hospital, as well as an associate professor at the Fred Hutchinson Cancer Center and the University of Washington in Seattle.

Reference: MS Thakar et al. Measuring the effect of newborn screening on survival after hematopoietic cell transplantation for severe combined immunodeficiency: a 36-year longitudinal study of the Primary Immune Deficiency Treatment Consortium. Lancet DOI:10.1016/S0140-6736(23)00731-6 (2023).

NIAID conducts and supports research—at the NIH, across the United States, and around the world—to study the causes of infectious and immune-mediated diseases, and to develop better ways to prevent, diagnose, and treat these diseases. News releases, fact sheets, and other NIAID-related materials are available on the NIAID website.

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