Objective: To systematically review nonpharmaceutical interventions aiming to enhance neurodevelopment in preterm children and adolescents (aged 4-18 years).

Method: A systematic review of the literature was conducted for all studies published up to May 1, 2022, across Medline, Web of Science, and PsycINFO databases. Studies were evaluated for inclusion by 2 independent reviewers using predetermined inclusion criteria. The Risk of Bias In Non-randomized Studies of Interventions and the Cochrane risk-of-bias tool for randomized trials (RoB 2) tools were used to assess bias in the selected studies.

Results: Of the 1778 articles identified, 23 were included. Quality assessment revealed moderate bias in 52.2%, low bias in 21.7%, and serious bias in 26.1%. The selected studies comprised 60.9% randomized controlled trials and 21.7% pre- versus postdesigns. Interventions included Cogmed Working Memory Training® (43.5%), BrainGame Brian (13%), physiotherapy (13%), and others (30.4%). Qualitative analysis showed the limited impact of interventions on neurodevelopmental outcomes in preterm children aged 4-18 years.

Conclusion: Despite recent efforts to use more rigorous methodologies, current research on school-age interventions for preterm neurodevelopment exhibits methodological limitations. There is a pressing need for well-designed, large-scale clinical trials to evaluate the efficacy of nonpharmaceutical interventions in this vulnerable population.