How Newborn Screening Closed a Survival Gap in SCID
In severe combined immunodeficiency (SCID), the strongest predictor of survival after a bone marrow transplant is whether an infant is still infection-free when the donor cells go in. Physicians knew that Black children with SCID were less likely to survive after a transplant than non-Hispanic White children, but not why.
A new study led by Lena Winestone, MD, MSHP, associate professor of pediatrics at UCSF, shows how newborn screening helped narrow that longstanding survival gap.
Four Decades of Transplant Data
Severe combined immunodeficiency, or SCID, is an extremely rare disease in which infants are born without a functioning immune system. Without a bone marrow transplant, it is typically fatal within the first year of life. How early SCID is detected can make a critical difference in a child’s health when they reach transplant.
Winestone's analysis, published in the Journal of Human Immunity, draws on four decades of data from nearly 800 children treated across North America through the Primary Immune Deficiency Treatment Consortium (PIDTC), a NIH-funded collaboration of over 40 centers led by UCSF pediatrician Chris Dvorak, MD.
“This large cohort allowed us to compare children diagnosed in different ways while accounting for when they were treated. Newborn screening for SCID was associated with earlier diagnosis, reduced chance of infection at transplant, and the elimination of survival disparities between Black and non-Hispanic White children,” explains Winestone.
Looking Beyond Biology
The overall difference in SCID survival was substantial. Five-year survival among Black children was 19 percentage points lower than among non-Hispanic White children. Black children faced more than twice the risk of death, even after accounting for the two strongest predictors of survival: age and infection status at transplant.
Disease biology couldn’t fully explain the differences. Black and Asian/Pacific Islander children were more likely to carry the SCID genotypes generally linked to the best transplant outcomes, not worse ones. Across the full cohort, infection status and age at transplant didn't differ significantly by race either.
When the researchers looked at how children were diagnosed, however, important differences emerged. Infants were traditionally diagnosed after they got ill, or less commonly, by a family history of SCID; since 2010, universal screening for SCID was increasingly adopted by state public health programs. Among those identified through family history, the delay from diagnosis to transplant for Black children was nearly twice as long as for non-Hispanic White children.
What Newborn Screening Changed
With newborn screening, the survival gap for Black patients disappeared entirely. Outcomes improved more broadly, too: since 2010, children identified through newborn screening had a five-year survival rate of 93 percent, compared with 85 percent for diagnosis through family history and 80 percent for diagnosis after illness.
“What stood out was that the survival disparity persisted in children diagnosed after they became sick,” says Winestone. “Newborn screening takes the burden of recognizing an incredibly rare disease off individual families and physicians. Every child is screened, and that allows us to intervene and prepare for transplant right away.”
Another finding reinforced the pattern. Native American children, who disproportionately carry a difficult-to-treat SCID genotype, nevertheless had favorable outcomes. The authors point in part to early access to newborn screening: it was piloted on the Navajo Nation and adopted reservation-wide in 2009. SCID newborn screening wasn't implemented in all 50 states until 2018.
From Pilot Program to National Policy
That early reach traces back to Jennifer Puck, MD, who helped develop the newborn screening test for SCID and bring it to Navajo communities, as well as California, where statewide screening started in 2010.
"Infants with SCID appear healthy at first, so population-based newborn screening was the only strategy to identify children before developing life-threatening infections. My hope is to see it reach every country, so every child with SCID can be identified and given timely treatment,” says Puck.
Puck's longtime collaborator, Morton Cowan, MD, has treated children with SCID at UCSF since performing one of the first such transplants in 1982. He brought Winestone into the project to leverage her expertise in health disparities, hoping to understand why outcomes varied by race.
What's Next
The gap hasn’t closed for everyone. Hispanic and Asian/Pacific Islander children have also experienced worse outcomes than average, and this study couldn't fully explain why. Winestone and colleagues are collecting self-reported race, ethnicity, and socioeconomic data directly from families to find out.
For infants with SCID, every day before transplant matters. By making early diagnosis systematic, newborn screening helps children reach lifesaving treatment sooner – reducing persistent gaps in survival.
The UCSF Division of Pediatric Allergy, Immunology, and Bone Marrow Transplantation has led the transformation of SCID from a fatal childhood disease to a curable one.
Authors: From the UCSF Department of Pediatrics are Lena Winestone, MD, Jennifer Puck, MD, Morton Cowan, MD, Chris Dvorak, MD, Morna Dorsey, MD, MS, and Elizabeth Dunn. For all authors, see the paper.
The Primary Immune Deficiency Treatment Consortium (PIDTC) is a previously funded research group of the Rare Diseases Clinical Research Network (RDCRN), which is funded by the National Institutes of Health (NIH). PIDTC received funding under grant number U54AI082973 as a collaboration between National Center for Advancing Translational Sciences (NCATS) and National Institute of Allergy and Infectious Diseases (NIAID). For all funding, see the paper.