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Early monitoring of motor developmental trajectories, strongly associated with neurodevelopmental outcome, is crucial for a timely identification of deviations from the reference path and the prediction of possible neurodevelopmental disorders (NDDs). However, the current understanding of the causal pathways through which motor difficulties emerge and evolve is limited by the lack of quantitative, standardised, and interpretative measures for infant motor development, and the need for a complex multidisciplinary examination of medical history. To overcome these limitations, we propose an approach based on Digital Twins (DTs) and innovative technology-based interpretative metrics for motor assessment to support holistic longitudinal evaluations of infant development. The DT enables the integration of multimodal data, including algorithms for data processing and artificial intelligence methods for data analysis, into a unique framework. Details on the DT ecosystem, internal model, and engine are provided. As a first step, a proof-of-concept application was implemented to show the feasibility of the framework, not yet exploring its full longitudinal potential. This initial study was based on already published data (17 full-term children, 21 preterm children born between 29 and 36 gestational weeks, and 8 very preterm children born\n                    <jats:inline-formula>\n                      <jats:tex-math>$$\\le$$<\/jats:tex-math>\n                    <\/jats:inline-formula>\n                    28 gestational weeks) and illustrates the integration of motor measures with clinical and cognitive information, their standardisation into the DT model, and a first set of advanced analyses. Given the relevance of the problem and the lack of standardised, structured follow-up protocols to monitor motor trajectory in preterm children, the proposed solution has the potential for a significant impact in clinical practice. Moreover, its usable and scalable design allows for easy adaptation to large, multi-center cohort studies targeting various infant clinical populations where motor function monitoring is essential (i.e. from children with rare neurological disorders to all newborns).\n                  <\/jats:p>","DOI":"10.1007\/s10916-025-02252-6","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T06:10:06Z","timestamp":1761199806000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Digital Twins for Monitoring Neuromotor Development in Preterm Infants: Conceptual Framework and Proof-of-concept Study"],"prefix":"10.1007","volume":"49","author":[{"given":"Sara","family":"Montagna","sequence":"first","affiliation":[]},{"given":"Rita","family":"Stagni","sequence":"additional","affiliation":[]},{"given":"Giada","family":"Pierucci","sequence":"additional","affiliation":[]},{"given":"Arianna","family":"Aceti","sequence":"additional","affiliation":[]},{"given":"Duccio Maria","family":"Cordelli","sequence":"additional","affiliation":[]},{"given":"Maria Cristina","family":"Bisi","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2025,10,23]]},"reference":[{"key":"2252_CR1","doi-asserted-by":"publisher","unstructured":"Zhao, Y., Liu, Y., Gao, X., Wang, D., Wang, N., Xie, R., Tong, X., He, Y., and Yang, L., Early biomarkers of neurodevelopmental disorders in preterm infants: protocol for a longitudinal cohort study. 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S.M. is an Associate Editor of the Journal of Medical Systems.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}},{"value":"The local Ethical Committee approved this study (ASL\n                      \n                      BO n\n                      \n                      0018081 08\/02\/2017), and informed consent was obtained from the participants\u2019 parents.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval and Consent to Participate"}}],"article-number":"143"}}