Because a delayed diagnosis of cystic fibrosis (CF) is detrimental and may be fatal, screening at birth has become routine in the Western world and has proven beneficial for many reasons, in addition to enabling prompt specialized care. Newborn screening (NBS) programs have elucidated the true incidence of CF in a variety of populations and enabled rapid genotype identification through the analysis of the cystic fibrosis transmembrane regulator (CFTR) gene. NBS studies also have revealed regional and population differences in CFTR variants and refuted the dogma that CF is a “white person’s disease”. But some regions have not yet implemented CF NBS, particularly in Asia where the disease prevalence has been uncertain. While the needs of a few low-and-middle-income countries are being addressed sequentially, one of the regions of greatest current interest is the Indian subcontinent because of recent data suggesting a higher incidence than that previously assumed, and clinical observations indicating tragic outcomes due to delayed diagnoses or failure to diagnose the disorder in young children. Thus, we conclude that the opportunities for research combined with service in the Indian subcontinent are urgent and potentially very impactful. Consequently, India is the last and best frontier for CF NBS, as we argue herein.

Early diagnosis of cystic fibrosis (CF) through newborn screening (NBS) improves clinical outcomes, but in countries like India, delayed diagnosis increases morbidity, mortality, and likely underestimates infant deaths from CF. We performed a retrospective study at a single center in south India from 2017 to 2025 reviewing children diagnosed with CF before one year of age. Patient demographic, clinical, and genetic data were analyzed to characterize early clinical features and identify factors linked to mortality. Of 56 infants diagnosed with CF, 59% survived (median current age 55 months) while 41% died (median age of death 5 months). Key clinical indicators included sibling death with CF-like symptoms, rapid weight loss, and persistent respiratory or nutritional complications. Mortality risk under one year was significantly linked to hypoalbuminemia (OR 9.7), severe malnutrition (OR 4.4), severe anemia (hemoglobin < 7 g/dL) requiring blood transfusions (OR 3.0), and peripheral edema (OR 4.2). A triad of anemia, hypoalbuminemia, and edema was found to strongly predict death (OR 4.2). Integrating clinical checklists of these manifestations into primary healthcare may improve prompt referrals for earlier diagnosis and treatment. Continued education and advocacy for NBS are essential to reduce potentially preventable CF-related deaths in young children.