Background: Preterm birth has major medical, psychological and socio-economic consequences worldwide. A recent systematic review suggests positive effects of music therapy (MT) on physiological measures of preterm infants and maternal anxiety, but methodologically rigorous studies including long-term follow-up of infant and parental outcomes are missing. Drawing upon caregivers' inherent resources, this study emphasizes caregiver involvement in MT to promote attuned, developmentally-appropriate musical interactions that may be of mutual benefit to infant and parent. This study will determine whether MT, as delivered by a qualified music therapist during neonatal intensive care unit (NICU) hospitalization and/or in home/municipal settings following discharge, is superior to standard care in improving bonding between primary caregivers and preterm infants, parent well-being and infant development.

Methods: Design: International multi-center, assessor-blind, 2x2 factorial, pragmatic randomized controlled trial. A feasibility study has been completed; ethical approval for the main trial is pending. Participants: 250 preterm infants and their parents. Intervention: MT focusing on singing specifically tailored to infant responses, will be delivered during NICU and/or during a post-discharge 6-month period. Primary outcome: Changes in mother-infant bonding until 6 months corrected age (CA), as measured by the Postpartum Bonding Questionnaire. Secondary outcomes: Mother-infant bonding at discharge and over 12 months CA; child development over 24 months; and parental depression, anxiety, and stress, and infant re-hospitalization, all over 12 months.

Discussion: This study fills a gap by measuring the long-term impact of MT for preterm infants/caregivers, and of MT beyond the hospital context. Outcomes related to highly involving parents in MT will directly inform the development of clinical practice in Scandinavia and other contexts with similar social welfare practices. By incorporating family-centered care, continuity of care, user involvement, and cultural relevance, this study can potentially contribute to improved quality of care for premature infants and their parents worldwide.

Inclusion Criteria (infants):

• born below 35 weeks gestational age
• determined by medical staff to have achieved sufficient medical stability to start MT
• likely to be hospitalized longer than 2 weeks from time of recruitment

Inclusion Criteria (parents):

• willing to engage in at least 2 of 3 MT sessions per week during NICU and/or in 5 of 7 MT post-discharge sessions, if randomized to receive MT
• live with reasonable commuting distance from the treating NICU
• sufficient understanding of the respective national language(s) to answer questionnaires and participate in MT

Exclusion Criteria (parents):

• documented mental illness or cognitive impairment that prevents them from being able to complete the study intervention or outcome assessments

To promote transparency and applicability of trial results and to facilitate re- analysis by other researchers while also protecting anonymity, de-identified individual patient data will be made available through the Norwegian Centre for Research Data (NSD).

Data collectors (for self-reports) and assessors (for observational measures) will be trained in assessment procedures and blinded to participant allocation. This will be ensured by using assessors from a different ward and by asking participants not to reveal their treatment assignments. Success of blinding will be verified.