Abstract
INTRODUCTION: Improving the quality of life for preterm children is a global health priority, given their vulnerability to neurocognitive impairments and adverse health consequences. Lack of posthospital 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 osteopathic manipulative treatment, on brain activity in moderately preterm infants using brain functional MRI (fMRI), computerised EEG and metabolomics. METHODS AND ANALYSIS: A 3-arm randomised 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 who do not require any intensive care treatments.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 between groups in blood oxygenation level dependent levels among different brain areas, specifically the anterior insula and the medial prefrontal cortex. Secondarily, we will explore the preterm brain's neural effects on EEG slow delta wave band. Metabolomics will provide data on the effects among the three groups on metabolic changes associated with touch interventions. ETHICS AND DISSEMINATION: Ethical 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 behaviour. 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 REGISTRATION NUMBER: NCT05853991.