BACKGROUND. The addition of Duchenne and Becker muscular dystrophy to the Recommended Uniform Screening Panel (RUSP) demands evidence of both the feasibility and the net benefit of population screening and follow-up. Progress toward DBMD newborn screening (NBS) remains hampered by inexperience with the creatine kinase MM isoform (CK-MM) assay and low numbers of presymptomatic infants identified, characterized, and treated. To address this evidence gap, the Early Check research study will offer voluntary expanded NBS for elevated CK-MM for all babies having standard NBS in North Carolina. Early Check will assess feasibility of population screening and follow-up while identifying and evaluating presymptomatic infants eligible for early treatment. While the sensitivity and specificity of CK-MM is improved over that of whole CK, conditions other than DBMD also associated with perinatal skeletal muscle damage could be identified. APPROACH. This presentation describes the follow-up plan for infants with elevated CK-MM to provide diagnostic testing, information, resources, support, care and referral for treatment. Screen-positive cases reflex to interrogation of the DMD gene with sequencing of a custom neuromuscular gene panel analyzed only if DMD studies are negative. Parents of babies with genetic diagnoses receive genetic counseling and developmental assessment by 3-months of age and a neuromuscular clinic research evaluation at 6 months, during which transition to clinical care is planned. For those without a genetic diagnosis, total CK will be measured. Parents of all babies with positive screening results–regardless of diagnostic outcome–are offered follow-up genetic counseling at 3 and 6 months, ongoing access to education and support materials, and invitation to the registry. CONCLUSIONS. Early Check's novel screening and follow-up approach for babies with elevated CK-MM will benefit families while contributing much-needed data to support a RUSP nomination.