Objective: Duchenne muscular dystrophy (DMD) is an X‐linked disorder resulting in progressive muscle weakness and atrophy, cardiomyopathy, and in late stages, cardiorespiratory impairment, and death. As treatments for DMD have expanded, a DMD newborn screening (NBS) pilot study was conducted in New York State to evaluate the feasibility and benefit of NBS for DMD and to provide an early pre‐symptomatic diagnosis.Methods: At participating hospitals, newborns were recruited to the pilot study, and consent was obtained to screen the newborn for DMD. The first‐tier screen measured creatine kinase‐MM (CK‐MM) in dried blood spot specimens submitted for routine NBS. Newborns with elevated CK‐MM were referred for genetic counseling and genetic testing. The latter included deletion/duplication analysis and next‐generation sequencing (NGS) of the DMD gene followed by NGS for a panel of neuromuscular conditions if no pathogenic variants were detected in the DMD gene.Results: In the two‐year pilot study, 36,781 newborns were screened with CK‐MM. Forty‐two newborns (25 male and 17 female) were screen positive and referred for genetic testing. Deletions or duplications in the DMD gene were detected in four male infants consistent with DMD or Becker muscular dystrophy. One female DMD carrier was identified.Interpretation: This study demonstrated that the state NBS program infrastructure and screening technologies we used are feasible to perform NBS for DMD. With an increasing number of treatment options, the clinical utility of early identification for affected newborns and their families lends support for NBS for this severe disease.

From 2007 to 2014 the New York State (NYS) Newborn Screening (NBS) program screened 2 million newborns for congenital adrenal hyperplasia (CAH). The data was analyzed to determine factors that affect 17α-hydroxyprogesterone levels and assist in developing algorithm changes that would improve the positive predictive value of the methodology being used. The concentration of 17-OHP in dried blood spots was measured using the AutoDELFIA Neonatal 17-OHP kit (Perkin Elmer, Turku, Finland). During the 8 year period of this study 2476 babies were referred, 105 babies were diagnosed with CAH (90 with the salt-wasting (SW), 8 with simple virilizing (SV), 5 with non-classical CAH, and 2 with another enzyme deficiency) and, 14 with possible CAH. Three false negative cases with SV-CAH were reported to the program. Of the total 108 known cases, 74 (69%) infants were detected by newborn screening in the absence of clinical information, or, known family history. The incidence of CAH in NYS is 1 in 18,170 with a ratio of SW to SV of 8.2:1. The incidence of CAH is lower in Black infants than in White, Hispanic and Asian infants. Despite a lower mean birth weight, female infants have a lower mean 17-OHP value than male infants and are under-represented in the referred category. As per other NBS programs the false positive rate is exacerbated by prematurity/low birth weight and by over-early specimen collection.

Duchenne muscular dystrophy (DMD) is the most common pediatric‐onset form of muscular dystrophy, occurring in 1 in 5,000 live male births. DMD is a multi‐system disease resulting in muscle weakness with progressive deterioration of skeletal, heart, and smooth muscle, and learning disabilities. Pathogenic/likely pathogenic (P/LP) variants in the DMD gene, which encodes dystrophin protein, cause dystrophinopathy. All males with a P/LP variant in the X‐linked DMD gene are expected to be affected. Two to 20% of female heterozygotes with a P/LP variant develop symptoms of dystrophinopathy ranging from mild muscle weakness to significant disability similar to Becker muscular dystrophy. Recently, with improvements in therapies and testing methodology, there is stronger evidence supporting newborn screening (NBS) for DMD for males and females because females may also develop symptoms. A consented pilot study to screen newborns for DMD was initiated in New York State (NYS) and conducted from 2019 to 2021. The identification of female carriers and the realization of the subsequent uncertainty of providers concerning follow‐up during the pilot led to the development of algorithms for screening and diagnosis of carrier females, including both NBS and cascade molecular testing of family members.

Newborn screening for congenital hypothyroidism remains challenging decades after broad implementation worldwide. Testing protocols are not uniform in terms of targets (TSH and/or T4) and protocols (parallel vs. sequential testing; one or two specimen collection times), and specificity (with or without collection of a second specimen) is overall poor. The purpose of this retrospective study is to investigate the potential impact of multivariate pattern recognition software (CLIR) to improve the post-analytical interpretation of screening results. Seven programs contributed reference data (N = 1,970,536) and two sets of true (TP, N = 1369 combined) and false (FP, N = 15,201) positive cases for validation and verification purposes, respectively. Data were adjusted for age at collection, birth weight, and location using polynomial regression models of the fifth degree to create three-dimensional regression surfaces. Customized Single Condition Tools and Dual Scatter Plots were created using CLIR to optimize the differential diagnosis between TP and FP cases in the validation set. Verification testing correctly identified 446/454 (98%) of the TP cases, and could have prevented 1931/5447 (35%) of the FP cases, with variable impact among locations (range 4% to 50%). CLIR tools either as made here or preferably standardized to the recommended uniform screening panel could improve performance of newborn screening for congenital hypothyroidism.

Advancements in therapies for Duchenne muscular dystrophy (DMD) have made diagnosis within the newborn period a high priority. We undertook a consortia approach to advance DMD newborn screening in the United States. This manuscript describes the formation of the Duchenne Newborn Screening Consortium, the development of the pilot protocols, data collection tools including parent surveys, and findings from the first year of a two-year pilot. The DMD pilot design is population-based recruitment of infants born in New York State. Data tools were developed to document the analytical and clinical validity of DMD NBS, capture parental attitudes, and collect longitudinal health information for diagnosed newborns. Data visualizations were updated monthly to inform the consortium on enrollment. After 12 months, 15,754 newborns were screened for DMD by the New York State Newborn Screening (NYS NBS) Program. One hundred and forty screened infants had borderline screening results, and sixteen infants were referred for molecular testing. Three male infants were diagnosed with dystrophinopathy. Data from the first year of a two-year NBS pilot for DMD demonstrate the feasibility of NBS for DMD. The consortia approach was found to be a useful model, and the Newborn Screening Translational Research Network’s data tools played a key role in describing the NBS pilot findings and engaging stakeholders.