Ten Years of Newborn Screening for Severe Combined Immunodeficiency (SCID) in Massachusetts.

BACKGROUND: Massachusetts began newborn screening (NBS) for severe combined immunodeficiency (SCID) using measurement of T-cell receptor excision circles (TRECs) from dried blood spots. OBJECTIVE: We describe developments and outcomes from the first 10 years of this program (February 1, 2009, to January 31, 2019). METHODS: TREC values, diagnostic, and outcome data from all patients screened for SCID were evaluated. RESULTS: NBS of 720,038 infants prompted immunologic evaluation of 237 (0.03%). Of 237, 9 were diagnosed with SCID/leaky SCID (4% of referrals vs 0.001% general population). Another 7 were diagnosed with other combined immunodeficiencies, and 3 with athymia. SCID/leaky SCID incidence was approximately 1 in 80,000, whereas approximately 1 in 51,000 had severe T-cell lymphopenia for which definitive treatment was indicated. All patients with SCID/leaky SCID underwent hematopoietic cell transplant or gene therapy with 100% survival. One patient with athymia underwent successful thymus transplant. No known cases of SCID were missed. Compared with outcomes from the 10 years before SCID NBS, survival trended higher (9 of 9 vs 4 of 7), likely due to a lower rate of infection before treatment. CONCLUSIONS: Our data support a single NBS testing-and-referral algorithm for all gestational ages. Despite lower median TREC values in premature infants, the majority for all ages are well above the TREC cutoff and the algorithm, which selects urgent (undetectable TREC) and repeatedly abnormal TREC values, minimizes referral. We also found that low naïve T-cell percentage is associated with a higher risk of SCID/CID, demonstrating the utility of memory/naïve T-cell phenotyping as part of follow-up flow cytometry.

Identification of High-Yield Targets for Antimicrobial Stewardship Program Efforts Within a Nonfreestanding Children's Hospital.

OBJECTIVES: Identify diagnoses with the highest likelihood of prompting antimicrobial stewardship program (ASP) recommendations and lowest probability of recommendation acceptance, investigate the impact of provider years in practice on recommendation receipt and acceptance, and simultaneously assess the influence of patient and provider-level variables associated with recommendations within a nonfreestanding children's hospital. METHODS: Retrospective cohort study of antibiotic courses reviewed by the ASP staff from December 1, 2014 to November 30, 2016. Poisson regression was used to detect associations between diagnoses, provider years in practice, and the probability of recommendation receipt and acceptance. Multivariable logistic regression was used to simultaneously examine the influence of patient and provider-level characteristics on recommendation probability. RESULTS: A total of 938 inpatient encounters and 1170 antibiotic courses were included. Diagnoses were associated with provider receipt (P < .001) and acceptance (P < .001) of recommendations, with ear, nose, and throat and/or sinopulmonary diagnoses most likely to prompt recommendations (56%; 95% confidence interval [CI], 48-64) and recommendations for neonatal and/or infant diagnoses accepted least often (67%; 95% CI, 58-76). No associations were initially found between provider experience and recommendation receipt or acceptance, although multivariable analysis revealed a trend between increasing years in practice and recommendation likelihood (P = .001). Vancomycin usage (64%; 95% CI, 56-72) and ear, nose, and throat and/or sinopulmonary diagnoses (56%; 95% CI, 47-65) had the highest probability of a recommendation. Sensitivity analyses revealed that use of diagnosis-related clinical practice guidelines decreased recommendations and increased acceptance rates, especially for the surgery diagnosis category. CONCLUSIONS: High-yield targets for ASP activities at our nonfreestanding children's hospital were identified. Clinical practice guidelines have the potential to decrease ASP workload, and their development should be particularly encouraged for ASPs with limited resources.