Limitations
neurodevelopmental and cognitive outcomes
RECRUITMENT
This study has limitations that have to be considered. First, our sample size is modest for a randomized clinical trial. This limitation is mainly related to a difficulty of recruitment of preterm infants and families into a research project during a stressful time in their life. In addition, this trial has been conducted, in part, during the Sars-Cov-2 pandemic, what has also imposed limitations regarding patients’ recruitment. Second, the number of times of music exposure during NICU stay can also be considered as limited. However, there are still no guidelines regarding the most adequate dosage to be used in music therapy. More studies concerning this question and correlating results with a quantification of music exposure should be ideally performed to better define dose effects. Third, due to diffusion imaging resolution and co-registration of the two images of one subject over time our analysis may be affected by partial volume effects. Nevertheless, since our analysis is automatized, any potential systematic errors would be similar among all subjects, thus allowing for a fair comparison between groups. Forth, the clinical significance behind brain structural alterations, such as FBA and NODDI metrics, following the music intervention, remains to be evaluated by investigating neurodevelopmental and cognitive outcomes in childhood, which are planned in our follow-up studies. Fifth, noise exposure during NICU stay was not quantified in this study and assumed to be equally distributed among groups, given the random allocation process and the similar topology of infants’ single rooms in neonatology. This would be an interesting feature to address in future studies. Finally, this study has compared a recorded instrumental music intervention to a similar condition but with absence of music during NICU stay. Parental presence and exposure to voice, including maternal singing, were considered to be equally distributed between groups, given the process of random allocation, and were not individually quantified. However, it might also hold an impact on preterm infant’s brain development. In general, more research is needed to compare instrumental music interventions to other sound interventions, such as maternal singing.