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Objectives: Newborn screening for severe combined immunodeficiency (SCID) was instituted in California in 2010. In the ensuing 6.5 years, 3 252 156 infants in the state had DNA from dried blood spots assayed for T-cell receptor excision circles (TRECs). Abnormal TREC results were followed-up with liquid blood testing for T-cell abnormalities. We report the performance of the SCID screening program and the outcomes of infants who were identified., Methods: Data that were reviewed and analyzed included demographics, nursery summaries, TREC and lymphocyte flow-cytometry values, and available follow-up, including clinical and genetic diagnoses, treatments, and outcomes., Results: Infants with clinically significant T-cell lymphopenia (TCL) were successfully identified at a rate of 1 in 15 300 births. Of these, 50 cases of SCID, or 1 in 65 000 births (95% confidence interval 1 in 51 000-1 in 90 000) were found. Prompt treatment led to 94% survival. Infants with non-SCID TCL were also identified, diagnosed and managed, including 4 with complete DiGeorge syndrome who received thymus transplants. Although no cases of typical SCID are known to have been missed, 2 infants with delayed-onset leaky SCID had normal neonatal TREC screens but came to clinical attention at 7 and 23 months of age., Conclusions: Population-based TREC testing, although unable to detect immune defects in which T cells are present at birth, is effective for identifying SCID and clinically important TCL with high sensitivity and specificity. The experience in California supports the rapid, widespread adoption of SCID newborn screening., Competing Interests: POTENTIAL CONFLICT OF INTEREST: Dr Markert developed technology for RVT-802, which has been licensed to Enzyvant Therapeutics GmbH. Dr Markert has received royalties from Enzyvant. Portions of Dr Markert and her research team’s salaries are being paid by the funding from Enzyvant. If the technology is commercially successful in the future, Dr Markert and Duke University may benefit financially. Dr Naides is employed by Quest Diagnostics. Donald Kohn is an inventor of a lentiviral vector for gene therapy of adenosine deaminase severe combined immunodeficiency, which Orchard Therapeutics Ltd has licensed from the University of California Regents; Dr Kohn is a consultant to Orchard Therapeutics Ltd and a member of its Scientific Advisory Board. Dr Cowan serves on the Scientific Advisory Boards for Homology Medicine, Inc, and Exogen, Inc, and on the Data and Safety Monitoring Board for bluebird bio, Inc. Dr Puck discloses spousal employment at a clinical DNA sequencing company, Invitae; the other authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2019 by the American Academy of Pediatrics.)

The rapid development of genomic sequencing technologies has decreased the cost of genetic analysis to the extent that it seems plausible that genome-scale sequencing could have widespread availability in pediatric care. Genomic sequencing provides a powerful diagnostic modality for patients who manifest symptoms of monogenic disease and an opportunity to detect health conditions before their development. However, many technical, clinical, ethical, and societal challenges should be addressed before such technology is widely deployed in pediatric practice. This article provides an overview of the Newborn Sequencing in Genomic Medicine and Public Health Consortium, which is investigating the application of genome-scale sequencing in newborns for both diagnosis and screening., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2017 by the American Academy of Pediatrics.)

Background and Objective: The potential application of whole-genome sequencing (WGS) to state-mandated standard newborn screening (NBS) challenges the traditional public health approach to NBS and raises ethical, policy, and clinical practice issues. This article examines the perspectives and values of diverse healthy pregnant women and parents of children diagnosed with a primary immunodeficiency disorder about traditional NBS and expanded NBS with the use of WGS., Methods: We conducted 4 focus groups (3 in English and 1 in Spanish) with socioeconomically and ethnically diverse pregnant women (n = 26), and a comparison group with parents of children diagnosed with a primary immunodeficiency disorder (n = 5)., Results: Pediatric policy-relevant themes that emerged from our analysis of the focus group data are presented within 4 categories: (1) perspectives on traditional NBS, (2) informed consent, (3) return of results, and (4) storage and retrieval of results. Analyses indicate that study participants desired greater inclusion in the NBS process. Despite an optimistic orientation to the potential benefits and limited harms likely to result from genomic applications of NBS, parents voiced concerns about privacy and control over test results. Limited trust in the medical system and the state-run NBS program informed these concerns., Conclusions: Expanded NBS with WGS for pediatricians may require management of more genetic conditions, including mutations that convey risk to both the child and parents for adult-onset disorders, and an informed-consent process to manage the genomic data and storage of blood spots. Attention to how these technologies are understood in diverse populations is needed for effective implementation., (Copyright © 2016 by the American Academy of Pediatrics.)