Objective: The Padovan-Method Neurofunctional Reorganization® is a promising approach in speech therapy treating neurodevelopmental disorders with traumatic or congenital origin. Its use is based on a long-time experience of certified therapists. However, its efficacy and safety has not been assessed in a systematic review. This report aims to gain evidence for the use of the therapy method. The review was registered (PROSPERO: CRD42020156124). Methods and Analysis: Guidelines of PRISMA, the Cochrane Collaboration Handbook, MECIR, and GRADE were followed. General databases (Cochrane Library, PubMed, AWMF, Anthromedics, etc.) and further 38 databases including grey literature were searched. Hand search was done additionally and contact to experts used to retrieve unpublished manuscripts. All trials investigating the effect of the method in comparison to either no intervention, alternative as state of the art, or placebo intervention in English, Portuguese, and German language were included. No restriction regarding study design was applied. Data related to the intervention outcome and the study method was extracted and analyzed independently. Risk of bias was assessed using ROBINS-I for non-RCTs, adherence to CARE-Guidelines was analyzed for case series or reports, and keeping the Declaration of Helsinki was checked for all items. Results are presented both in evidence profiles and summary of findings tables according to GRADE. Results: Amongst 98 records assessed for eligibility, four studies and 14 case reports were identified with a total of n = 196 participants. Duration of reported interventions was between 2 days and 2 years. Microcephalia, down-syndrome, unspecified neurological disorders, and myofunctional disorders were main conditions of the patients with neurodevelopmental disorders. Only indirect overlapping of operationalized criteria was found. Conclusions are therefore limited. Conclusion: The Padovan-Method® is a holistic therapy approach claiming its feasibility to a large group of disorders making a proof of efficacy difficult. An application of therapy according to the Padovan-Method® by trained therapists might be considered by clinicians (weak recommendation) and a contribution to a relief of symptoms or improvements of condition of named conditions might be gained. Therefore, development and validation of therapy protocols and further investigation are required.

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