Serial Neuroimaging and Term-equivalent Age Neurodevelopmental Outcomes of Very Preterm Infants Receiving Tailored Neuropromotive Support in the NICU

Background: Infants born very preterm (VP) undergo rapid brain growth and development prior to term-equivalent age (TEA) while in the neonatal intensive care unit (NICU), a critical window for intervention. Early MRI imaging has the potential to identify infants with neurological injury and may help tailor early neuropromotive interventions to optimize neurodevelopmental outcomes while in the NICU prior to TEA.

Aims:
1. Use early MRI to stratify VP infants into low-risk or high-risk groups based on degree of brain injury and tailor rehabilitative support according to risk category.
2. Explore associations between rehabilitative intervention, total and regional brain growth and short and long-term outcomes of preterm infants.

Methods: This is a prospective cohort study of infants born <33 weeks gestation age (GA) in a level-III NICU at Brigham and Women’s Hospital. Infants assigned to the exposure group are stratified into low- and high-risk groups based on early MRI and compared with a standard of care group. The exposure is based on the Supporting and Enhancing NICU Sensory Experiences (SENSE) program, with tailored weekly multisensory plans intended to be implemented preferentially by parents with staff and developmental therapists’ support. For infants in the high-risk group, the SENSE program is enhanced with additional, intensive motor and other developmental therapy (SENSE-plus). Serial MRIs are obtained at least three times until TEA, along with routine cranial ultrasound (CUS) per unit guidelines. At TEA, MRI scans are scored using the Kidokoro system and neurodevelopmental status is assessed by the test of infant motor performance (TIMP) and the Hammersmith neonatal neurological exam (HNNE) score. Results: 52 infants have completed the study, including 27 in the SENSE exposure group (19 low-risk and 8 high-risk) and 25 in the standard care (SC) group (non-exposed). Of the 144 MRIs performed, 56 were early (30-34 weeks GA) scans and 57 were at TEA (37-41 weeks GA). The characteristics of the two groups were similar between the exposed and unexposed groups, with mean GA and BW being 29.06 weeks and 1213.93 grams in the exposure group and 28.51 weeks and 1203.56 grams in the non-exposed group. Additionally, the average length of stay for infants in the exposure group was 77 days while for the non-exposure group it was 88 days. In the SENSE low-risk subgroup, 17 (89%) infants had TIMP scores in the Average range compared to 10 (83%) infants in the SC low risk subgroup. In the SENSE high-risk subgroup, 6 (75%) infants had a TIMP score in the Average range compared to 6 (67%) infants in the SC high-risk subgroup. All participants assigned to the SENSE exposure group received 75% or more of the intended multisensory experiences, indicating feasibility with no documented adverse effects. Further advanced MRI and long-term neurodevelopmental outcomes data collection and analyses are in progress. Conclusions: Preliminary analyses at TEA indicate that a neuropromotive program tailored based on the level of neurological risk informed by early brain MRI is feasible, well-tolerated, and shows potential to improve outcomes of infants born very preterm.