The Impact of Touch Interventions on Brain Activity in Moderately Preterm Infants: study protocol for a pilot randomized controlled trial

IntroductionImproving the quality of life for preterm children is a global health priority, given their vulnerability to neurocognitive impairments and adverse health consequences. Lack of post-hospital care further exacerbates these risks, necessitating effective interventions during the neonatal period. This protocol for a pilot study aims to investigate the effects of touch interventions, including physiotherapy and manual therapy (OMT), on brain activity in moderately preterm infants using brain functional magnetic resonance imaging (fMRI), computerized electroencephalogram (EEG), and metabolomics. Methods and analysisA 3-arm randomized sham-controlled trial will be conducted with 15 infants per experimental group. The study will include stable preterm infants born between 32.0 and 33.6 weeks of gestational age (GA) who do not require other intensive care treatments. Exclusion criteria encompass preterm infants born before 32.0 weeks GA, those born after 33.6 weeks GA, and newborns with respiratory and neurological pathologies. The study aims to assess the impact of touch interventions on brain activity and metabolic sequelae. Using fMRI will primarily examine the pre-post changes in functional connectivity of the brain, while EEG will secondarily explore the preterm brains neural effects on slow delta waves band. Metabolomics will provide data on the effects among the 3 groups on metabolic changes associated with touch interventions. Ethics and disseminationEthical approval has been obtained from the Ethics Committee of the local health agency in Milan (CET 449-2024). Understanding the effects of touch interventions on brain activity in moderately preterm infants, without needs of intensive care, can contribute to improving their clinical outcomes and promoting their growth, development, and social behavior. Findings from this pilot study will pave the way for future research, enabling the development of evidence-based interventions to enhance preterm infants well-being and long-term outcomes. Trial registrationThe research protocol has been registered on ClinicalTrials.gov (NCT05853991) Article SummaryStrengths and limitations of this study O_LIThe study presents rigorous study design with blinding measures to determine the effect of therapeutic touch as compared to affective and static touch C_LIO_LIThe study employs a combination of high-resolution 3T fMRI, electrophysiology, and metabolomic analysis, providing objective and quantifiable biomarkers of neural and metabolomic responses to touch interventions. C_LIO_LIThe study recruits a small sample size, which therefore might limited the generalizability of results C_LIO_LIThe study assesses immediate post-intervention effects but does not include long-term neurodevelopmental follow-up C_LI