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Background  Previous systematic reviews have examined preterm infants’ long-term neurodevelopment after neonatal intensive care unit (NICU) discharge, although none have explored the effectiveness of interventions on preterm infants’ neurodevelopment during NICU hospitalization. The aim of this review is to evaluate whether interventions, i.e., sensory stimulation, parental involvement, and control of environment, improve preterm infants’ neurodevelopment during their NICU hospitalization.    Methods  Experimental studies such as randomized controlled/clinical trials (RCTs) and cluster RCT will be included in this systematic review. Selected studies will be published in English or in French, in the past 15 years from 2002 to 2017. The following electronic databases will be searched to locate relevant studies: CINAHL, MEDLINE, PubMed, EMBASE (OVID), Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science. For all steps in selecting studies, agreement will be reached between two experts in neonatology. Data extraction will be performed independently by the two same experts and will then be compared. The Cochrane assessment tool will be used to screen the studies for risk of bias. A meta-analysis will be performed if the included studies are sufficiently homogeneous. Results will be analyzed using a standardized mean difference (with a 95% confidence interval). Statistical heterogeneity will be evaluated using the  χ   2  test at the significance level of 0.1 and the  I   2  with the classification suggested by PRISMA-P. If possible, subgroup analyses will be carried out considering preterm infants’ gestational age, length of NICU hospitalization, and the characteristics of the intervention such as who delivered it, the type, the dose, the frequency, and the duration. Data synthesis will be performed using the RevMan 5.1 software. Publication bias and selection of variables in publication will be examined using the graphical method of funnel plot and with the statistical test of Egger. Quality of the evidence of all outcomes will be assessed using the Grades of Recommendations Assessment, Development and Evaluation (GRADE) Working Group.    Discussion  The results of this systematic review will highlight which interventions are effective for promoting preterm infants’ neurodevelopment during NICU hospitalization and will contribute to the body of knowledge in neonatal care by providing guidance for NICU clinical practice and research.    Systematic review registration  PROSPERO  CRD42017047072Electronic supplementary material  The online version of this article (10.1186/s13643-017-0613-5) contains supplementary material, which is available to authorized users.

Effectiveness of interventions during NICU hospitalization on the neurodevelopment of preterm infants: a systematic review protocol