Measuring the Effect of Newborn Screening on Survival After Hematopoietic Cell Transplantation for Severe Combined Immunodeficiency: A 36-Year Longitudinal Study From the Primary Immune Deficiency Treatment Consortium

To explore the effects of the implementation of population-based newborn screening for Severe Combined Immunodeficiency (SCID) on overall survival in patients with SCID after hematopoietic cell transplantation (HCT).After exclusions, the study included 902 children with SCID from 34 Primary Immune Deficiency Treatment Consortium sites in the United States and Canada who underwent allogeneic HCT between January 1, 1982 and December 31, 2018.Data such as sex, race and ethnicity, SCID type and genotype, trigger for diagnosis (newborn screening, family history, or clinical illness), age at HCT, time interval of HCT, infection status at HCT, transplant-related data, and date of death were collected. The Kaplan-Meier method was used to estimate overall survival. A risk adjustment model using Cox proportional hazards regression was used to analyze risk factors for HCT outcomes.Before 2010, the 5-year overall survival rate for children with SCID was 72% to 73%, with 32% to 33% of SCID diagnoses made because of preventative testing by family history, and 65% to 67% of diagnoses resulting from presenting clinical illness. Between 2010 and 2018, the 5-year overall survival rate significantly increased to 87%. Forty-nine percent of these diagnoses were made because of positive SCID newborn screening, whereas 33% of diagnoses resulted from presenting clinical illness. Since 2010, the 5-year overall survival rate was significantly higher in children diagnosed with SCID via newborn screening (92.5%) compared with children whose diagnosis resulted from presenting clinical illness (79.9%) or family history (85.4%). Risk factors for increased mortality, including active infection, age 3.5 months or older at HCT, Black or African American race, and specific SCID genotypes, were identified using multivariable analysis.There is marked benefit in population-based newborn SCID screening on overall survival of patients by facilitating early HCT and preventing infection.To our knowledge, this is the largest longitudinal multi-institutional study that has demonstrated the positive impact of population-based newborn SCID screening on the survival of patients with SCID who underwent HCT. This has led to a paradigm shift in the declining number of presenting infections and a higher frequency of HCT being performed before 3.5 months of age. Delayed SCID diagnosis can be a significant public health cost burden as these children will experience repeat hospitalizations, morbidity, and mortality. Newborn screening not only alleviates cost but also effectively treats these patients. Interestingly, African American children with SCID had the highest risk of death. Further studies are warranted to investigate factors contributing to disparities in care for this patient population.