2.1. Participants

All eligible infants born VPT enrolled in the “Does Timing Matter? Supporting Play, Exploration, and Early Development Intervention” trial (SPEEDI2—ClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT03518736","term_id":"NCT03518736"}}NCT03518736) in early 2020 were approached for enrolment in the optional MRI substudy until late 2021. Eligible infants received care in one of the three participating neonatal intensive care units (NICUs), lived within 100 miles of the participating hospitals, were born <29 weeks of gestation, and were medically stable and off ventilator support between 35 and 42 weeks of gestation when the baseline developmental assessment was complete. Exclusion criteria included: non-English-speaking families or a diagnosis of genetic abnormality at the time of enrolment. Additional information on selection, allocation concealment and randomisation is available in the protocol paper for the primary SPEEDI2 intervention trial [42]. This study was approved by the Human Subjects Board at Virginia Commonwealth University and a caregiver provided consent for their child’s participation in the primary trial, supplemental imaging study, and access to their child’s medical records.

Six infants were enrolled in this supplemental study which added non-sedated MRI scanning to a 3-arm clinical trial (usual care, SPEEDI2 early starting in the NICU, SPEEDI2 late starting at 15 weeks post-baseline). The MRI scans were completed at four time points. Visit 1 consisted of a) a baseline assessment of developmental and neurological function completed in the NICU as soon as the infant was medically stable and b) an MRI completed within 72 h after NICU discharge. In effect, ‘Visit 1’ involved 2 visits, which were carried out to ensure the same outpatient scanner was used for all MRIs. The remaining visits were scheduled based on the time from the baseline: 15 weeks post-baseline (Visit 2), 30 weeks post-baseline (Visit 3), and 12 months post-baseline (Visit 4). With the exception of the first MRI, developmental outcomes were assessed on the same day. Six infants completed MRI within 72 h of NICU discharge (Visit 1), 5 infants completed MRI at Visit 2 (one missed due to COVID-19), 5 infants completed MRI at Visit 3 (one parent opted out of further MRI to avoid removing new earrings) and 4 infants completed MRI at Visit 4 (one infant did not remain asleep). Enrolled infants were randomised into one of 3 groups: usual care (Infants 3 and 4), SPEEDI2 early (Infants 2 and 6), SPEEDI2 late (Infants 1 and 5). Infant 5’s family opted out of intervention before starting, so this infant is presented with the usual care group, and SPEEDI2 early (n = 2) and SPEEDI2 late (n = 1) groups are collapsed and presented as the SPEEDI2 intervention group.