Abstract

Expanded newborn screening (ENBS) has substantially improved the early identification of inherited metabolic diseases, enabling timely interventions that have transformed the prognosis of many affected infants. However, the effectiveness of ENBS relies on a complex multidisciplinary pathway extending well beyond laboratory analysis, involving healthcare professionals with diverse roles as well as families who must understand, interpret, and respond to screening information. At every stage of this process, cognitive biases and heuristics may influence perception, judgment, communication, and decision-making, potentially affecting diagnostic accuracy, follow-up, and family experience. This narrative case-based work examines the role of cognitive biases throughout the ENBS pathway, from parental information provided during pregnancy and dried blood spot collection to laboratory interpretation, communication of positive or uncertain results, confirmatory testing, dietary management, and long-term clinical follow-up. Particular attention is devoted to the different professionals involved – including nurses, midwives, laboratory scientists, metabolic physicians and dietitians – as well as to the cognitive processes that may shape parental understanding, information seeking, and healthcare decisions after positive screening results. The work also discusses practical examples of common cognitive biases encountered in ENBS and explores evidence-based strategies to mitigate their impact, including reflective practice, standardized communication, multidisciplinary collaboration, and cognitive debiasing interventions. Recognizing the influence of cognitive biases represents an important opportunity to strengthen diagnostic reasoning, improve communication with families, reduce avoidable errors, and promote more equitable and patient-centered newborn screening programs.